Digital Commons Network^™

Intravenous Ascorbic Acid To Prevent And Treat Cancer-Associated Sepsis?, Thomas E. Ichim, Boris Minev, Todd Braciak, Brandon Luna, Ron Hunninghake, Nina A. Mikirova, James A. Jackson, Michael J. Gonzalez, Jorge R. Miranda-Massari, Doru T. Alexandrescu, Constantin A. Dasanu, Vladimir Bogin, Janis Ancans, R. Brian Stevens, Boris Markosian, James Koropatnick, Chien-Shing Chen, Neil H. Riordan

Department of Surgery Faculty Publications

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis …

The Influence Of Interleukin-4 On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Stacey L. Brickson, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Despite a complex cascade of cellular events to reconstruct the damaged extracellular matrix, ligament healing results in a mechanically inferior scarred ligament. During normal healing, granulation tissue expands into any residual normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise and an inefficient repair process. To control creeping substitution and possibly enhance the repair process, the antiinflammatory cytokine, interleukin-4 (IL-4), was administered to rats before and after rupture of their medial collateral ligaments. In vitro experiments showed a time-dependent effect on fibroblast proliferation after IL-4 treatment. In vivo treatments with IL-4 (100 ng/mL IV) …

Ultrasound Echo Is Related To Stress And Strain In Tendon, Sarah Duenwald, Hirohito Kobayashi, Kayt E. Frisch, Roderic Lakes, Ray Vanderby Jr.

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

The mechanical behavior of tendons has been well studied in vitro. A noninvasive method to acquire mechanical data would be highly beneficial. Elastography has been a promising method of gathering in vivo tissue mechanical behavior, but it has inherent limitations. This study presents acoustoelasticity as an alternative ultrasound-based method of measuring tendon stress and strain by reporting a relationship between ultrasonic echo intensity (B-mode ultrasound image brightness) and mechanical behavior of tendon in vitro. Porcine digital flexor tendons were cyclically loaded in a mechanical testing system while an ultrasonic echo response was recorded. We report that echo intensity …

Intravenous Erythropoietin In Patients With St-Segment Elevation Myocardial Infarction - Reveal: A Randomized Controlled Trial, S. S. Najjar, S. V. Rao, C. Melloni, S. V. Raman, T. J. Povsic, L. Melton, G. W. Barsness, K. Prather, L. Gruberg, R. A. Harrington, +10 Additional Authors

Journal Articles

Context: Acute ST-segment elevation myocardial infarction (STEMI) is a leading cause of morbidity and mortality. In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. Objective: To evaluate the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI. Design, Setting, and Patients: A prospective, randomized, double-blind, placebo-controlled trial with a dose-escalation safety phase and a single dose (60 000 U of epoetin alfa) efficacy phase; the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial was conducted at 28 US sites between October …

The Nurse's Knowledge Of Blood Conservation As A Part Of Blood Management, Lindsey Putnam Austin

Nursing Theses and Capstone Projects

Medicine has historically regarded blood transfusion as an integral component of major surgery or illness. However, clinical studies have shown that allogeneic blood transfusions are associated with increased morbidity and decreased survival. Knowledge of this research and the concepts of blood conservation so as to avoid unnecessary blood transfusions is needed in order to deliver holistic care and serve as patient advocate. This knowledge reaches every specialty of nursing care.

This study of the nurse's knowledge of blood conservation as a part of blood management utilizes The Conservation Model developed by Myra E. Levine in 1973. Levine's work is a …

The Influence Of Macrophage Depletion On Ligament Healing, Connie S. Chamberlain, Ellen M. Leiferman, Kayt E. Frisch, Sijian Wang, Xipei Yang, Nico Van Rooijen, Geoff S. Baer, Stacey L. Brickson, Ray Vanderby

Faculty Publications - Biomedical, Mechanical, and Civil Engineering

Despite a complex cascade of cellular events to reconstruct damaged extracellular matrix (ECM), ligament healing results in a mechanically inferior, scar-like tissue. During normal healing, the number of macrophages significantly increases within the wound site. Then, granulation tissue expands into any residual, normal ligamentous tissue (creeping substitution), resulting in a larger region of healing, greater mechanical compromise, and an inefficient repair process. To study the effects of macrophages on the repair process, bilateral, surgical rupture of their medial collateral ligaments (MCLs) was done on rats. Treatment animals received liposome-encapsulated clodronate, 2 days before rupture to ablate phagocytosing macrophages. Ligaments were …

Is Thrombolytic Therapy Safe When Used To Treat Elderly Patients?, Daniel Yaeger

The Science Journal of the Lander College of Arts and Sciences

Recently, research has been conducted to determine if thrombolytic therapy works to dissolve clots and if it is a safe treatment option. The specific purpose of this study is to determine if thrombolytic therapy is safe for use in the elderly. This study was conducted by reviewing the relevant literature that has been published from the time that research began to test the usefulness of thrombolytic therapy. Numerous journals were examined to ensure impartiality and emerge with an unbiased conclusion. The journals were discovered using PubMed article finder, using Google as a search engine, and by scrutinizing relevant references found …

Identification Of Genes Involved In Hematopoietic Stem Cell Differentiation And Leukemia Differentiation And Leukemia, Jasjeet Bhullar

Theses, Dissertations and Capstones

Hematopoiesis is maintained by a proper balance between self renewal and multipotent differentiation of the hematopoietic stem cells (HSC). Acute myelogenous leukemia (AML) is characterized by the blockage in the differentiation of HSC, while self renewal and proliferation is preserved. It is important to understand the mechanisms involved in the inhibition of hematopoietic differentiation and maintenance of the HSC state in order to develop better therapies for AML. In these studies I have explored the role of Hsp90, omega-3 fatty acids and YB-1 in hematopoietic differentiation. EML, a hematopoietic precursor cell line, was used as a model for the hematopoietic …

The Effects Of Smoking On Pregnant Women, Meir Cohen

The Science Journal of the Lander College of Arts and Sciences

Smoking during pregnancy is accepted as the most significant avoidable risk factor for an unsuccessful pregnancy result. Smoking is linked with fetal growth restriction, and increasing evidence also suggests that smoking can cause stillbirth, preterm birth, placental abruption, and possibly sudden infant death syndrome. Smoking during pregnancy is also associated with enhanced risks of spontaneous abortions, ectopic pregnancies, and placenta previa, and it might increase risks of behavioral disorders in childhood. Studies have shown with randomized controlled trials, that smoking intervention during pregnancy has had limited success. Smoking during pregnancy continues to be an important risk factor for maternal and …

Pharmacotherapy And Pregnancy: Highlights From The Third International Conference For Individualized Pharmacotherapy In Pregnancy, David M. Haas, Beverly Gallauresi, Kristine Shields, Deborah S. Zeitlin, Shannon M. Clark, Mary F. Herbert, Zhaoxia Ren, Srikanth C. Nallani, Eric M. Meslin, Karen B. Feibus, Gideon Koren, W. Scott Goebel, Thomas Easterling, Scott C. Denne, David A. Flockhart, Jamie L. Renbarger

Scholarship and Professional Work – COPHS

To address provider struggles to provide evidence-based, rational drug therapy to pregnant women, this third Conference was convened to highlight the current progress and research in the field. Speakers from academic centers, industry, and governmental institutions spoke about: the Food and Drug Administration’s role in pregnancy pharmacology and the new labeling initiative; drug registries in pregnancy; the pharmacist’s role in medication use in pregnancy; therapeutic areas such as preterm labor, gestational diabetes, nausea and vomiting in pregnancy, and hypertension; breast-feeding and medications; ethical challenges for consent in pregnancy drug studies; the potential for cord blood banks; and concerns about the …

Research Annual Report 2010, Children's Mercy Hospital

Research Annual Reports

Annual report of the research at Children's Mercy Hospital in Kansas City MO, a pediatric medical center.

Differentiation Of Embryonic Stem Cells Into Fibroblast-Like Cells In Three-Dimensional Type I Collagen Gel Cultures, Shinsaku Togo, Tadashi Sato, Hisatoshi Sugiura, Xingqi Wang, Hesham Basma, Amy J. Nelson, Xiangde Liu, Tom W. Bargar, J. Graham Sharp, Stephen I. Rennard

Journal Articles: Pulmonary & Critical Care Med

Fibroblasts are heterogeneous mesenchymal cells that play important roles in the production and maintenance of extracellular matrix. Although their heterogeneity is recognized, progenitor progeny relationships among fibroblasts and the factors that control fibroblast differentiation are poorly defined. The current study was designed to develop a reliable method that would permit in vitro differentiation of fibroblast-like cells from human and murine embryonic stem cells (ESCs). Undifferentiated ESCs were differentiated into embryoid bodies (EBs) with differentiation media. EBs were then cast into type I collagen gels and cultured for 21 d with basal media. The spindle-shaped cells that subsequently grew from the …

Mccraken Knows Ulcers And Parasitic Worms, Aldemaro Romero Jr.

Publications and Research

No abstract provided.

Ouabain Stimulates A Na+/K+-Atpase-Mediated Sfk-Activated Signalling Pathway That Regulates Tight Junction Function In The Mouse Blastocyst., Holly Giannatselis, Michele Calder, Andrew J Watson

Obstetrics & Gynaecology Publications

The Na(+)/K(+)-ATPase plays a pivotal role during preimplantation development; it establishes a trans-epithelial ionic gradient that facilitates the formation of the fluid-filled blastocyst cavity, crucial for implantation and successful pregnancy. The Na(+)/K(+)-ATPase is also implicated in regulating tight junctions and cardiotonic steroid (CTS)-induced signal transduction via SRC. We investigated the expression of SRC family kinase (SFK) members, Src and Yes, during preimplantation development and determined whether SFK activity is required for blastocyst formation. Embryos were collected following super-ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding Src and Yes throughout preimplantation development. SRC and …

The Role Of The Sparc Acidic Domain And Egf-Like Module In Glioma Migration, Invasion, And Signaling, Heather M. Mcclung

Wayne State University Dissertations

THE ROLE OF THE SPARC ACIDIC DOMAIN AND EGF-LIKE MODULE IN GLIOMA MIGRATION, INVASION, AND SIGNALING

HEATHER M. MCCLUNG

Advisor: Sandra A. Rempel, Ph.D.

Major: Pharmacology

Degree: Doctor of Philosophy

We have previously shown that Secreted Protein Acidic and Rich in Cysteine (SPARC) is upregulated in all astrocytoma grades and increases tumor cell migration and invasion. It is thought that different domains within the protein may regulate SPARC functions, suggesting domain-specific targeting to inhibit invasion. To enhance our understanding of SPARC-mediated invasion, we first confirm, at the protein level, our previous cDNA array results, that SPARC increases expression of the …

Estrogen Sulfotransferase (Sult1e1) Expression And Function In Mcf10a-Series Breast Epithelial Cells: Role As A Modifier Of Breast Carcinogenesis And Regulation By Proliferation State, Jiaqi Fu

Wayne State University Dissertations

Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. TaqMan Gene Expression assays were used to profile the mRNA expression of estrogen receptor (ERα and ERβ) and estrogen metabolism enzymes including cytosolic sulfotransferases (SULT1E1, SULT1A1, SULT2A1, and SULT2B1), steroid sulfatase (STS), aromatase (CYP19), 17β-hydroxysteroid dehydrogenases (17βHSD1 and 2), CYP1B1, and catechol-O-methyltransferase (COMT) in an MCF10A-derived lineage cell culture model for basal-like human breast cancer progression and in ERα-positive luminal MCF7 breast cancer cells. Low levels of ERα and ERβ mRNA were present in MCF10A-derived cell lines. SULT1E1 mRNA was more abundant in confluent relative to subconfluent MCF10A …

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Osteochondral Grafting Of Knee Joint Using Mosaicplasty, Muhammad Abdul Wajid, Muhammad Idrees Shah, Mohsin E. Azam, Tashfeen Ahmad

Section of Orthopaedic Surgery

Focal cartilage defects of articular surface-traumatic and degenerative are difficult to treat, thus a variety of surgical techniques have been developed and reported for treatment of such defects. Procedures such as Priddies perforations, microfracture, abrasion chondroplasty have shown long-term results which are often less than adequate. One of the reasons is that all these techniques lead to the formation of fibrocartilage which has inferior mechanical properties as compared to the native hyaline cartilage. Mosaicplasty is a procedure which aims at replacing the lost articular cartilage with hyaline cartilage including underlying bone support, thus providing adequate stability to the cartilage and …

Heat Shock Protein Induced Protection Against Cisplatin-Induced Hair Cell Death, Tiffany Gray Baker

MUSC Theses and Dissertations

Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin include nephrotoxicity and ototoxicity. Cisplatin's ototoxic effect results in part from damage to and death of cochlear hair cells. Mechanisms underlying cisplatin-induced hair cell death are poorly understood and have been attributed to DNA damage, oxidative stress, and inflammation. This study was designed to determine the role of p53 in cisplatin-induced hair cell death and to investigate heat shock proteins (HSPs) as potential protectants against cisplatin-induced hair cell death using adult mouse utricle as …

Tissue-Specific Regulation Of Mouse Microrna Genes In Endoderm-Derived Tissues., Yan Gao, Jonathan Schug, Lindsay B Mckenna, John Le Lay, Klaus H Kaestner, Linda E Greenbaum

Department of Cancer Biology Faculty Papers

MicroRNAs fine-tune the activity of hundreds of protein-coding genes. The identification of tissue-specific microRNAs and their promoters has been constrained by the limited sensitivity of prior microRNA quantification methods. Here, we determine the entire microRNAome of three endoderm-derived tissues, liver, jejunum and pancreas, using ultra-high throughput sequencing. Although many microRNA genes are expressed at comparable levels, 162 microRNAs exhibited striking tissue-specificity. After mapping the putative promoters for these microRNA genes using H3K4me3 histone occupancy, we analyzed the regulatory modules of 63 microRNAs differentially expressed between liver and jejunum or pancreas. We determined that the same transcriptional regulatory mechanisms govern tissue-specific …

Map Kinases Phosphorylate Spf45 And Regulate Its Alternative Splicing Function: Insights Onto Phosphorylation-Dependent And -Independent Effects In Ovarian Cancer Cells, Adnan Al-Ayoubi

MUSC Theses and Dissertations

Alternative pre-mRNA splicing increases proteome diversity and is important in the behavior of cells in health and disease. The processes that regulate alternative premRNA splicing are diverse and include regulation of splicing factors by phosphorylation. Here we report that the pre-mRNA alternative splicing factor SPF45 is a novel substrate of ERK, JNK and p38 MAP kinases in ovarian cancer cells. Using mutational analysis and phospho-specific antibodies, we demonstrate that MAP kinases phosphorylate SPF45 on Thr71 and Ser222 and that phosphorylation in cells is induced by a number of extracellular stimuli including PMA, EGF, serum, H20 2 and UV. Exon 6 …

Requirement Of Argininosuccinate Lyase For Systemic Nitric Oxide Production, Ayelet Erez, Sandesh Cs. Nagamani, Oleg A. Shchelochkov, Muralidhar H. Premkumar, Philippe M. Campeau Campeau, Yuqing Chen, Harsha K. Garg, Li Li, Asad Mian, Terry K. Bertin, Jennifer O. Black, Heng Zeng, Yaoping Tang, Anilkumar K. Reddy, Marshall Summar, William E. O’Brien, David G. Harrison, William E. Mitch, Juan C. Marini, Judy L. Aschner, Nathan S. Bryan, Brendan Lee

Department of Emergency Medicine

Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in …

Hypertensive Nephropathy Treatment By Heart-Protecting Musk Pill: A Study Of Anti-Inflammatory Therapy For Target Organ Damage Of Hypertension, Dengke Tian, Shuang Ling, Gangling Chen, Yajuan Li, Jun Liu, Murad Ferid, Ka Bian

Faculty, Staff and Student Publications

This study was designed to investigate the protective effect of the heart-protecting musk pill (HMP) on inflammatory injury of kidney from spontaneously hypertensive rat (SHR). Male SHRs aged 4 weeks were divided into SHR model group, HMP low-dosage group (13.5 mg/kg), and HMP high-dosage group (40 mg/kg). Age-matched Wistar-Kyoto rats were used as normal control. All rats were killed at 12 weeks of age. Tail-cuff method and enzyme-linked immunosorbent assay were used to determine rat systolic blood pressure and angiotensin II (Ang II) contents, respectively. Renal inflammatory damage was evaluated by the following parameters: protein expressions of inflammatory cytokines, carbonyl …

Targeted Decorin Gene Therapy Delivered With Adeno-Associated Virus Effectively Retards Corneal Neovascularization In Vivo, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Gregory S. Schultz, John W. Cowden, Ashish Tandon

Pharmacy Faculty Articles and Research

Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 μl; 5x10^12 vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and …

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …

Toward Personalized Cell Therapies: Autologous Menstrual Blood Cells For Stroke, Maria Carolina O. Rodrigues, Loren E. Glover, Nathan Weinbren, Jessica A. Rizzi, Kazutaka Shinozuka, Naoki Tajiri, Yuji Kaneko, Paul R. Sanberg, Julie G. Allickson, Nicole Kuzmin-Nichols, Svitlana Garbuzova-Davis, Julio Cesar Voltarelli, Eduardo Cruz, Cesar V. Borlongan

Neurosurgery and Brain Repair Faculty Publications

Cell therapy has been established as an important field of research with considerable progress in the last years. At the same time, the progressive aging of the population has highlighted the importance of discovering therapeutic alternatives for diseases of high incidence and disability, such as stroke. Menstrual blood is a recently discovered source of stem cells with potential relevance for the treatment of stroke. Migration to the infarct site, modulation of the inflammatory reaction, secretion of neurotrophic factors, and possible differentiation warrant these cells as therapeutic tools. We here propose the use of autologous menstrual blood cells in the restorative …

Population Pharmacokinetic (Pk) And Pharmacodynamic (Pd) Modeling Of Ticarcillin‐Clavulanate In Pediatric Cf Patients, Jeffery T. Zobell, Chris Stockmann, D. C. Young, Jared Cash, Catherine M.T. Sherwin, Michael G. Spigarelli, Barbara A. Chatfield, Krow Ampofo

Pediatrics Faculty Publications

No abstract provided.

The Mechanosensory Role Of Primary Cilia In Vascular Hypertension, Surya M. Nauli, Xingjian Jin, Beerend P. Hierck

Pharmacy Faculty Articles and Research

Local regulation of vascular tone plays an important role in cardiovascular control of blood pressure. Aside from chemical or hormonal regulations, this local homeostasis is highly regulated by fluid-shear stress. It was previously unclear how vascular endothelial cells were able to sense fluid-shear stress. The cellular functions of mechanosensory cilia within vascular system have emerged recently. In particular, hypertension is insidious and remains a continuous problem that evolves during the course of polycystic kidney disease (PKD). The basic and clinical perspectives on primary cilia are discussed with regard to the pathogenesis of hypertension in PKD.

Thiazolyl N-Benzyl-Substituted Acetamide Derivatives: Synthesis, Src Kinase Inhibitory And Anticancer Activities, Asal Fallah-Tafti, Alireza Foroumadi, Rakesh Tiwari, Amir Nasrolahi Shirazi, David G. Hangauer, Yahao Bu, Tahmineh Akbarzadeh, Keykavous Parang, Abbas Shafiee

Pharmacy Faculty Articles and Research

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure-activity relationship, a number of N-benzyl substituted (2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI50 values of 1.34 μM and 2.30 M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. …