Digital Commons Network^™

Targeting Human Central Nervous System Protein Kinases: An Isoform Selective P38Αmapk Inhibitor That Attenuates Disease Progression In Alzheimer's Disease Mouse Models, Saktimayee M. Roy, Valerie L. Grum-Tokars, James P. Schavocky, Faisal Saeed, Agnieszka Staniszewski, Andrew F. Teich, Ottavio Arancio, Adam D. Bachstetter, Scott J. Webster, Linda J. Van Eldik, George Minasov, Wayne F. Anderson, Jeffrey C. Pelletier, D. Martin Watterson

Spinal Cord and Brain Injury Research Center Faculty Publications

The first kinase inhibitor drug approval in 2001 initiated a remarkable decade of tyrosine kinase inhibitor drugs for oncology indications, but a void exists for serine/threonine protein kinase inhibitor drugs and central nervous system indications. Stress kinases are of special interest in neurological and neuropsychiatric disorders due to their involvement in synaptic dysfunction and complex disease susceptibility. Clinical and preclinical evidence implicates the stress related kinase p38αMAPK as a potential neurotherapeutic target, but isoform selective p38αMAPK inhibitor candidates are lacking and the mixed kinase inhibitor drugs that are promising in peripheral tissue disease indications have limitations for neurologic indications. Therefore, …

Chaperone Hsp47 Drives Malignant Growth And Invasion By Modulating An Ecm Gene Network, Jieqing Zhu, Gaofeng Xiong, Hanjiang Fu, B. Mark Evers, Binhua P. Zhou, Ren Xu

Markey Cancer Center Faculty Publications

The extracellular matrix (ECM) is a determining factor in the tumor microenvironment that restrains or promotes malignant growth. In this report, we show how the molecular chaperone protein Hsp47 functions as a nodal hub in regulating an ECM gene transcription network. A transcription network analysis showed that Hsp47 expression was activated during breast cancer development and progression. Hsp47 silencing reprogrammed human breast cancer cells to form growth-arrested and/or noninvasive structures in 3D cultures, and to limit tumor growth in xenograft assays by reducing deposition of collagen and fibronectin. Coexpression network analysis also showed that levels of microRNA(miR)-29b and -29c were …

Polymeric Nanoparticle-Based Delivery Of Microrna-199a-3p Inhibits Proliferation And Growth Of Osteosarcoma Cells, Linlin Zhang, Arun K. Iyer, Xiaoqian Yang, Eisuke Kobayashi, Yuqi Guo, Henry Mankin, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Our prior screening of microRNAs (miRs) identified that miR-199a-3p expression is reduced in osteosarcoma cells, one of the most common types of bone tumor. miR-199a-3p exhibited functions of tumor cell growth inhibition, suggesting the potential application of miR-199a-3p as an anticancer agent. In the study reported here, we designed and developed a lipid-modified dextran-based polymeric nanoparticle platform for encapsulation of miRs, and determined the efficiency and efficacy of delivering miR-199a-3p into osteosarcoma cells. In addition, another potent miR, let-7a, which also displayed tumor suppressive ability, was selected as a candidate miR for evaluation. Fluorescence microscopy studies and real-time polymerase chain …

Attenuation Of Traumatic Brain Injury-Induced Cognitive Impairment In Mice By Targeting Increased Cytokine Levels With A Small Molecule Experimental Therapeutic, Adam D. Bachstetter, Scott J. Webster, Danielle S. Goulding, Jonathan E. Morton, D. Martin Watterson, Linda J. Van Eldik

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: Evidence from clinical studies and preclinical animal models suggests that proinflammatory cytokine overproduction is a potential driving force for pathology progression in traumatic brain injury (TBI). This raises the possibility that selective targeting of the overactive cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, may be a useful therapeutic approach. MW151 is a CNS-penetrant, small molecule experimental therapeutic that selectively restores injury- or disease-induced overproduction of proinflammatory cytokines towards homeostasis. We previously reported that MW151 administered post-injury (p.i.) is efficacious in a closed head injury (CHI) model of diffuse TBI in mice. Here we test …

Practical Management Of Anticoagulation In Patients With Atrial Fibrillation., Richard J Kovacs, Greg C Flaker, Sherry J Saxonhouse, John U. Doherty, Kim K Birtcher, Adam Cuker, Bruce L Davidson, Robert P Giugliano, Christopher B Granger, Amir K Jaffer, Bella H Mehta, Edith Nutescu, Kim A Williams

Department of Medicine Faculty Papers

Anticoagulation for atrial fibrillation has become more complex due to the introduction of new anticoagulant agents, the number and kinds of patients requiring therapy, and the interactions of those patients in the matrix of care. The management of anticoagulation has become a "team sport" involving multiple specialties in multiple sites of care. The American College of Cardiology, through the College's Anticoagulation Initiative, convened a roundtable of experts from multiple specialties to discuss topics important to the management of patients requiring anticoagulation and to make expert recommendations on issues such as the initiation and interruption of anticoagulation, quality of anticoagulation care, …

Successful Isolation Of Viable Adipose-Derived Stem Cells From Human Adipose Tissue Subject To Long-Term Cryopreservation: Positive Implications For Adult Stem Cell-Based Therapeutics In Patients Of Advanced Age., Sean Devitt, Md, Cynthia M Carter, Raia Dierov, Scott Weiss, Robert P Gersch, Ivona Percec

Jefferson Hospital Staff Papers and Presentations

We examined cell isolation, viability, and growth in adipose-derived stem cells harvested from whole adipose tissue subject to different cryopreservation lengths (2-1159 days) from patients of varying ages (26-62 years). Subcutaneous abdominal adipose tissue was excised during abdominoplasties and was cryopreserved. The viability and number of adipose-derived stem cells isolated were measured after initial isolation and after 9, 18, and 28 days of growth. Data were analyzed with respect to cryopreservation duration and patient age. Significantly more viable cells were initially isolated from tissue cryopreserved2 years, irrespective of patient age. However, this difference did not persist with continued growth and …

Com Outlook Spring 2015, College Of Osteopathic Medicine

COM Outlook

No abstract provided.

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Certain General Anesthetics Used In Pediatrics Hinder Neurological Development In Infants, Michael R. Hirschi

Selected Honors Theses

General anesthetics act by either blocking N-methyl-d-aspartate (NMDA) receptors or over stimulating γ-aminobutyric acid (GABA) receptors.^1–3 The actions of these receptors are responsible for the anesthetized state and are also crucial in the neurological development of infants.^2,4–8 Animal studies, although limited, provide vital information about general anesthesia’s neurotoxicity its hindrance of neurological development. Exposure to general anesthesia can severely hinder proper neuronal migration, synaptogenesis, and can drastically increase neuronal apoptosis in infant animals.^9–16 General anesthetics are more neurotoxic to infant animals in combination compared to individually.^10,16,17 Additionally, multiple exposures to general anesthesia tend to have compounding …

The Therapeutic Role Of Turmeric In Treatment And Prevention Of Alzheimer’S Disease, Rylan M. Mcquade

Selected Honors Theses

As a devastating neurological condition that expends millions of lives each year, Alzheimer’s disease (AD) is a subject of intense investigation.¹ Although AD has been known for over a century, the precise mechanisms that underlie AD pathogenesis and development are still poorly understood. The Alzheimer phenotype is typified by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs), causing researchers to notice several key enzymes implicated in this process.¹ Most notable are β and γ secretases (which drive Aβ plaque production) and phospholipase

A₂ (which stimulates major cascade activation through the specific cleavage of fatty acyl esters). …

Ubiquitous L1 Mosaicism In Hippocampal Neurons., Kyle R. Upton, Daniel J. Gerhardt, J. Samuel Jesuadian, Sandra R. Richardson, Francisco J. Sánchez-Luque, Gabriela O. Bodea, Adam D. Ewing, Carmen Salvador-Palomeque, Marjo S. Van Der Knaap, Paul M. Brennan, Adeline Vanderver, Geoffrey J. Faulkner

Neurology Faculty Publications

Somatic LINE-1 (L1) retrotransposition during neurogenesis is a potential source of genotypic variation among neurons. As a neurogenic niche, the hippocampus supports pronounced L1 activity. However, the basal parameters and biological impact of L1-driven mosaicism remain unclear. Here, we performed single-cell retrotransposon capture sequencing (RC-seq) on individual human hippocampal neurons and glia, as well as cortical neurons. An estimated 13.7 somatic L1 insertions occurred per hippocampal neuron and carried the sequence hallmarks of target-primed reverse transcription. Notably, hippocampal neuron L1 insertions were specifically enriched in transcribed neuronal stem cell enhancers and hippocampus genes, increasing their probability of functional relevance. In …

Physical Actvity In Pregnant Rat Dams Reduces Mammary Tumor Formation In Offspring, Leon Clah

Open Access Theses

Breast cancer is the most frequently diagnosed cancer and a leading cause of cancer death among women. Lifestyle factors such as physical activity and diet play a role in attenuating the incidence of breast cancer. Current research is beginning to show that exercise during pregnancy can convey long term health benefits to offspring. In light of these studies, the goal of this project was to determine if maternal physical activity during pregnancy could lead to reduced mammary tumor development in female offspring. Towards this goal, female Sprague Dawley rats were divided into two groups, sedentary and exercise, with the exercise …

Oncolog, Volume 60, Number 04, April 2015, Jill Delsigne, Joe Munch, Bryan Tutt, Sarah Bronson

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• Multidisciplinary Globe-Sparing Treatment for Lacrimal Gland Carcinoma Preserves Vision and Minimizes Morbidity: Until recently, the treatment of lacrimal gland carcinoma almost always required removal of the eye. But for some patients with these tumors, globe-sparing surgery followed by radiation therapy can preserve vision and decrease ocular morbidity and facial disfigurement.
• Novel Trial Design Streamlines Development of Breast Cancer Therapies: Developing a cancer-fighting drug can take around a billion dollars and a dozen or more years. Even then, fail in clinical trials. To identify effective cancer therapies more quickly and efficiently, researchers have tuned to an innovative clinical model in which …

Transient Cardiovascular Hemodynamics In A Patient-Specific Arterial System, Jr Rodward Hewlin

Dissertations

The ultimate goal of the present study is to aid in the development of tools to assist in the treatment of cardiovascular disease. Gaining an understanding of hemodynamic parameters for medical implants allow clinicians to have some patient-specific proposals for intervention planning. In the present study a full cardiovascular experimental phantom and digital phantom (CFD model) was fabricated to study: (1) the effects of local hemodynamics on global hemodynamics, (2) the effects of transition from bed-rest to upright position, and (3) transport of dye (drug delivery) in the arterial system. Computational three dimensional (3-D) models (designs A, B, and C) …

Does The Addition Of Dexamethasone To Local Anesthetic Used For Peripheral Nerve Block Prolong Analgesia In The Surgical Patient?, Janice M. Oliveira

Nurse Anesthesia MSNA Student Capstones

Pain after orthopedic surgery can be intense. Many anesthesia providers and orthopedic surgeons support the use of peripheral nerve blockade to assist in decreasing the amount of pain a patient may experience post operatively. Select medication adjuncts are being added to peripheral nerve blocks to prolong analgesia. The research presented here focuses on the addition of dexamethasone to peripheral nerve blocks to prolong analgesia. Dexamethasone is a synthetic glucocorticoid that acts as an anti-inflammatory. It has been shown to inhibit the release of inflammatory mediators such as, interleukins and cytokines, facilitating the release of anti-inflammatory mediators, decreasing postoperative pain. Recent …

Knee Morphometric Risk Factors For Acute Anterior Cruciate Ligament Injury In Skeletally Immature Patients, Kenneth Aaron Shaw, Brian S. Dunoski, Neil J. Mardis, Donna M. Pacicca

Manuscripts, Articles, Book Chapters and Other Papers

© 2015, The Author(s).

Study design: Retrospective, case–control.

Purpose: Knee morphometric risk factors for noncontact anterior cruciate ligament (ACL) injury have been a popular topic with skeletally mature patients. Little research has focused on the skeletally immature, with conflicting conclusions. This study performs a comprehensive analysis of identified parameters thought to predispose to ACL injury in a skeletally immature cohort.

Methods: A retrospective review of pediatric patients undergoing knee magnetic resonance imaging (MRI) was performed over a 4-year period. Inclusionary criteria included mid-substance ACL disruption, skeletal immaturity, noncontact injury, without associated ligamentous disruption, and no medical condition associated with ligamentous …

The Effect Of Exercise Training On Skeletal Muscle Gdnf Content And Neuromuscular Physiology In A Mouse Model Of Amyotrophic Lateral Sclerosis., Nicole Carpp

Honors Theses

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease accompanied by the loss of motor neurons, leading to paralysis and death. Glial cell line-derived neurotrophic factor (GDNF) promotes neuron health and function and has been proposed as a therapeutic treatment for ALS. GDNF protein expression in skeletal muscle is regulated by physical activity. The aim of this study was to determine if low intensity exercise would increase GDNF expression in skeletal muscle and slow degeneration of motor neurons in a mouse model of ALS. Following the first sign of disease onset, transgenic ALS mice were randomly assigned to one of three …

Detection Of Phlpp1Α/Β In Human And Mouse Brain By Different Anti-Phlpp1 Antibodies, Travis C. Jackson, Hülya Bayir, Milos D. Ikonomovic, Keri Janesko-Feldman, Zaichuan Mi, Tianyan Gao, Edwin K. Jackson, Patrick M. Kochanek

Markey Cancer Center Faculty Publications

Pleckstrin homology domain and leucine rich repeat protein phosphatase 1 (PHLPP1) is a member of the serine/threonine family of phosphatases. It has been studied in organs including brain, heart, pancreas, adipose, breast, and prostate. Human PHLPP1 encodes two splice variants - PHLPP1α (~140-150 kDa) and PHLPP1β (~180-190 kDa). Commercial antibodies are widely used to characterize PHLPP1 proteins in cells/tissues. Here we validate five different antibodies to detect PHLPP1α/β by Western blot using PHLPP1 WT/KO mice. All antibodies recognize PHLPP1β in brain. Only a single antibody (Cosmo Bio Co) detects PHLPP1α (~145-150 kDa). The other four antibodies detect a non-specific signal …

Complementary And Alternative Medicine In Cancer Prevention And Therapy., Peng Cao, Senthamil R Selvan, Esra Küpeli Akkol, Ning Wang, Hongjun Yang, Xiaolan Cheng

Department of Medical Oncology Faculty Papers

No abstract provided.

Babies First: Ensuring Proper Infant Nutrition During Emergencies, Abigail M. Alonso

Independent Study Project (ISP) Collection

Background: Breastfeeding is the best source of nutrition for an infant, living in all regions and cultures. Recommendations apply across the board, from developed nations to refugee camps, from women with HIV to those with time constraints regarding feeding. There also exists a complex relationship between corporations that provide BMS and the NGOs working to promote breastfeeding in emergency situations amongst vulnerable populations.

Objective: The objective of this paper is to expose breastfeeding promotion, using the Dadaab camps in Northeastern Kenya as a case study of IYCF programs and support of breastfeeding among low-literacy populations with an emphasis on women …

Categorizing Fetal Heart Rate Variability With And Without Visual Aids, Amanda Jane Ashdown

Psychology Theses & Dissertations

This present study examined the ability of clinicians and novices to correctly categorize fetal heart rate (FHR) variability with and without the use of exemplars. Clinicians and undergraduate students were asked to inspect FHR images and determine into which of four categories they belonged. Each participant took part in three conditions: one in which they were provided exemplars of prototypical FHR variability to use during their categorization task, another in which they were provided exemplars of nonprototypical FHR variability to use in their task, and a control condition in which no exemplars were available. The results showed that experts were …

Pathways Involved In Interleukin-1Β-Mediated Murine Cardiomyocyte Apoptosis, Yi Shen, Jie Qin, Peili Bu

The Texas Heart Institute Journal

Accumulating evidence suggests that interleukin-1 (IL-1) signaling plays an essential role in the pathogenesis of heart failure by inducing cardiomyocyte apoptosis, but the mechanisms of this process are poorly defined. We further explored these molecular pathways.

We isolated cardiomyocytes from neonatal mice and then cultured and stimulated them with murine IL-1β in vitro. Cell apoptotic ratios were measured by means of flow cytometry. Expression of effector molecules was analyzed by means of enzyme-linked immunosorbent assay, Western blotting, and real-time quantitative polymerase chain reaction. The results showed that IL-1β induced murine cardiomyocyte apoptosis through a release of cytochrome c into cytoplasm …

Focused Ultrasound For Treatment Of Bone Tumours., Dario B. Rodrigues, Paul R. Stauffer, David Vrba, Mark Hurwitz, Md

Department of Radiation Oncology Faculty Papers

PURPOSE: Focused ultrasound (FUS) is a modality with rapidly expanding applications across the field of medicine. Treatment of bone lesions with FUS including both benign and malignant tumours has been an active area of investigation. Recently, as a result of a successful phase III trial, magnetic resonance-guided FUS is now a standardised option for treatment of painful bone metastases. This report reviews the clinical applications amenable to treatment with FUS and provides background on FUS and image guidance techniques, results of clinical studies, and future directions.

METHODS: A comprehensive literature search and review of abstracts presented at the recently completed …

The Emerging Role Of Ng2 In Pediatric Diffuse Intrinsic Pontine Glioma., Sridevi Yadavilli, Joseph Scafidi, Oren J. Becher, Amanda M. Saratsis, Rebecca L. Hiner, Madhuri Kambhampati, Santi Mariarita, Tobey J. Macdonald, Kari-Elise Codispoti, Suresh N. Magge, Jyoti K. Jaiswal, Roger J. Packer, Javad Nazarian

Neurology Faculty Publications

Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis and are poorly understood brain cancers. Receptor tyrosine kinases stabilized by neuron-glial antigen 2 (NG2) protein are known to induce gliomagenesis. Here, we investigated NG2 expression in a cohort of DIPG specimens (n= 50). We demonstrate NG2 expression in the majority of DIPG specimens tested and determine that tumors harboring histone 3.3 mutation express the highest NG2 levels. We further demonstrate that microRNA 129-2 (miR129-2) is downregulated and hypermethylated in human DIPGs, resulting in the increased expression of NG2. Treatment with 5-Azacytidine, a methyltransferase inhibitor, results in NG2 downregulation in DIPG …

G9a Is Essential For Emt-Mediated Metastasis And Maintenance Of Cancer Stem Cell-Like Characters In Head And Neck Squamous Cell Carcinoma, Shuli Liu, Dongxia Ye, Wenzheng Guo, Wenwen Yu, Yue He, Jingzhou Hu, Yanan Wang, Ling Zhang, Yueling Liao, Hongyong Song, Shuangshuang Zhong, Dongliang Xu, Huijing Yin, Beibei Sun, Xiaofei Wang, Jingyi Liu, Yadi Wu, Binhua P. Zhou, Zhiyuan Zhang, Jiong Deng

Markey Cancer Center Faculty Publications

Head and neck squamous cell carcinoma (HNSCC) is a particularly aggressive cancer with poor prognosis, largely due to lymph node metastasis and local recurrence. Emerging evidence suggests that epithelial-to-mesenchymal transition (EMT) is important for cancer metastasis, and correlated with increased cancer stem cells (CSCs) characteristics. However, the mechanisms underlying metastasis to lymph nodes in HNSCC is poorly defined. In this study, we show that E-cadherin repression correlates with cancer metastasis and poor prognosis in HNSCC. We found that G9a, a histone methyltransferase, interacts with Snail and mediates Snail-induced transcriptional repression of E-cadherin and EMT, through methylation of histone H3 lysine-9 …

Preliminary Analysis Of In Utero Low-Level Arsenic Exposure And Fetal Growth Using Biometric Measurements Extracted From Fetal Ultrasound Reports, Matthew A. Davis, John Higgins, Zhigang Li, Diane Gilbert-Diamond, Emily R. Baker, Amar Das, Margaret R. Karagas

Dartmouth Scholarship

Background: Early life exposure to arsenic is associated with decreased birth weight in highly exposed populations but little is known about effects of low-level arsenic exposure on growth in utero.

Methods: Using a sample of 272 pregnancies from New Hampshire we obtained biometric measurements directly from fetal ultrasound reports commonly found in electronic medical records. We used information extraction methods to develop and validate an automated approach for mining biometric measurements from the text of clinical reports. As a preliminary analysis, we examined associations between in utero low-level arsenic exposure (as measured by maternal urinary arsenic concentration) and fetal growth …

Burden Of Periprosthetic Joint Infection And Its Treatment On Kidney Function

Rothman Institute Conference Posters

Introduction:

Patients with periprosthetic joint infection (PJI) are subjected to several potentially nephrotoxic conditions such as acute and chronic systemic inflammatory reactions, multiple surgical procedures and noxious antibiotics. This study aims to investigate 1) the incidence and severity of kidney injury in patients undergoing surgical treatment for PJI, 2) whether the number of surgeries affects renal function in PJI patients and 3) the potential risk factors for kidney injury.

Ppm1a Regulates Antiviral Signaling By Antagonizing Tbk1-Mediated Sting Phosphorylation And Aggregation, Zexing Li, Ge Liu, Liwei Sun, Yan Teng, Xuejiang Guo, Jianhang Jia, Jiahao Sha, Xiao Yang, Dahua Chen, Qinmiao Sun

Markey Cancer Center Faculty Publications

Stimulator of interferon genes (STING, also known as MITA and ERIS) is critical in protecting the host against DNA pathogen invasion. However, the molecular mechanism underlying the regulation of STING remains unclear. Here, we show that PPM1A negatively regulates antiviral signaling by targeting STING in its phosphatase activity-dependent manner, and in a line with this, PPM1A catalytically dephosphorylates STING and TBK1 in vitro. Importantly, we provide evidence that whereas TBK1 promotes STING aggregation in a phosphorylation-dependent manner, PPM1A antagonizes STING aggregation by dephosphorylating both STING and TBK1, emphasizing that phosphorylation is crucial for the efficient activation of STING. Our …

Metformin Prevents Aggressive Ovarian Cancer Growth Driven By High-Energy Diet: Similarity With Calorie Restriction, Zaid Al-Wahab, Ismail Mert, Calvin Tebbe, Jasdeep Chhina, Miriana Hijaz, Robert T. Morris, Rouba Ali-Fehmi, Shailendra Giri, Adnan Munkarah, Ramandeep Rattan

Department of Obstetrics and Gynecology Research Publications

Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking …

The Flavonoid Nobiletin Inhibits Tumor Growth And Angiogenesis Of Ovarian Cancers Via The Akt Pathway, Jianchu Chen, Allen Y. Chen, Haizhi Huang, Xingqian Ye, William D. Rollyson, Haley E. Perry, Kathleen C. Brown, Yon Rojanasakul, Gary O. Rankin, Piyali Dasgupta, Yi Charlie Chen

Pharmaceutical Science and Research

Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving …