Cancer Biology Commons^™

The Effect Of Grapefruit Intake On Endogenous Serum Estrogen Levels In Postmenopausal Women, Kristine R. Monroe, Frank Z. Stanczyk, Kathleen Hill-Besinque, Malcolm C. Pike

Pharmacy Faculty Articles and Research

Although grapefruit intake leads to elevated serum estrogen levels when hormones are taken orally, there are no published data on the effect on endogenous levels. We conducted a pilot dietary intervention study among healthy postmenopausal volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were recruited through the Love/Avon Army of Women. The study consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr after grapefruit intake were collected during an acute-phase study …

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge …

Anti-Proliferative Effects Of Garcinia Fruits In Breast Cancer Cells, Harini Anandhi Senthilkumar

Dissertations, Theses, and Capstone Projects

Breast cancer continues to be the second leading cause of death in women, even with the recent advances in research that has led to an improved understanding of molecular pathways and targets. Increasing mortality due to recurrence and lack of targeted drugs, especially in aggressive breast cancer subtypes such as triple negative breast cancer, has gained attention from the research community. With nearly 50% of the commonly used cancer drugs being sourced from plants, bioactive small molecules derived from a natural origin have immense potential as therapeutics. This study focuses on the anti-proliferative activities of benzophenones isolated from the edible …

Target Engagement Imaging Of Parp Inhibitors In Small-Cell Lung Cancer, Brandon Carney, Susanne Kossatz, Benjamin H. Lok, Valentina Schneeberger, Kishore K. Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A. Weber, Charles M. Rudin, John T. Poirier, Thomas Reiner

Publications and Research

Insufficient chemotherapy response and rapid disease progression remain concerns for smallcell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo. We measure PARP1/2 inhibition …

Inhibition Of Dihydrotestosterone Synthesis In Prostate Cancer By Combined Frontdoor And Backdoor Pathway Blockade, Michael V. Fiandalo, John J. Stocking, Elena A. Pop, John H. Wilton, Krystin M. Mantione, Yun Li, Kristopher M. Attwood, Gissou Azabdaftari, Yue Wu, David S. Watt, Elizabeth M. Wilson, James L. Mohler

Center for Pharmaceutical Research and Innovation Faculty Publications

Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues. Mass spectrometry data showed combined treatment using catalytically inactive 3α-oxidoreductase mutants and the 5α-reductase inhibitor, dutasteride, decreased DHT levels in CaP cells better than dutasteride alone. Combined blockade …

A Predictive 7-Gene Assay And Prognostic Protein Biomarkers For Non-Small Cell Lung Cancer, Nancy Lan Guo, Afshin Dowlati, Rebecca A. Raese, Chunlin Dong, Guoan Chen, David G. Beer, Justine Shaffer, Salvi Singh, Ujala Bokhary, Lin Liu, John Howingtown, Thomas Hensing, Yong Qian

Faculty & Staff Scholarship

This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non- small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic tar- gets. Patients and methods: The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples.

Results: A 7-gene …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

Mlk Book Read 2018 (Research Materials), Holy Cross Libraries

Library Resources for Campus Events

A bibliography of resources available through the Holy Cross Libraries which provide additional information related to the MLK Winter Book Read, based on the best-seller “The Immortal LIfe of Henrietta Lacks” by Rebecca Skoot.

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …

The Identification And Segmentation Of Astrocytoma Prior To Critical Mass, By Means Of A Volumetric/Subregion Regression Analysis Of Normal And Neoplastic Brain Tissue, Lyn Higgins

Electronic Theses and Dissertations

As the underlying cause of Glioblastoma Multiforme (GBM) is presently unclear, this research implements a new approach to identifying and segmenting plausible instances of GBM prior to critical mass. Grade-IV Astrocytoma, or GBM, is an aggressive and malignant cancer arising from star-shaped glial cells, or astrocytes, where the astrocytes, functionally, assist in the support and protection of neurons within the central nervous system and spinal cord. Subsequently, our motivation for researching the ability to recognize GBM is that the underlying cause of the mutation is presently unclear, leading to the operative that GBM is only detectable through a combination of …

Design And Evaluation Of Gemini Surfactant-Based Lipoplexes Modified With Cell-Binding Peptide For Targeted Gene Therapy, Waleed Mohammed-Saeid, Rania Soudy, Richa Tikoo, Kamaljit Kaur, Ronald E. Verrall, Ildiko Badea

Pharmacy Faculty Articles and Research

Purpose Achieving successful gene therapy requires delivery of a gene vector specifically to the targeted tissue with efficient expression and a good safety profile. The objective of this work was to develop, characterize and determine if a novel gemini surfactant-based lipoplex systems, modified with a cancer-targeting peptide p18-4, could serve this role. Methods The targeting peptide p18-4 was either chemically coupled to a gemini surfactant backbone or physically co-formulated with the lipoplexes. The influence of targeting ligand and formulation strategies on essential physicochemical properties of the lipoplexes was evaluated by dynamic light scattering and small angle X-ray scattering techniques. In …

Cold Atmospheric Plasma As A Potential Tool For Multiple Myeloma Treatment, Dehui Xu, Yujing Xu, Qingjie Cui, Dingxin Liu, Zhijie Liu, Xiaohua Wang, Yanjie Yang, Niaojuan Feng, Rong Liang, Hailan Chen, Kai Ye, Michael G. Kong

Bioelectrics Publications

Multiple myeloma (MM) is a fatal and incurable hematological malignancy thus new therapy need to be developed. Cold atmospheric plasma, a new technology that could generate various active species, could efficiently induce various tumor cells apoptosis. More details about the interaction of plasma and tumor cells need to be addressed before the application of gas plasma in clinical cancer treatment. In this study, we demonstrate that He+O₂ plasma could efficiently induce myeloma cell apoptosis through the activation of CD95 and downstream caspase cascades. Extracellular and intracellular reactive oxygen species (ROS) accumulation is essential for CD95-mediated cell apoptosis in response …

Enhanced Electric Pulse Technology For The Ablation Of Pancreatic Cancer, Siqi Guo, Niculina I. Burcus, Chelsea M. Edelblute, James Hornef, Chunqi Jiang, Karl Schoenbach, Richard Heller, Stephen J. Beebe

Bioelectrics Publications

Electric pulse based technology has been developed and studied as a non-thermal ablation method for local control of pancreatic cancer. Irreversible electroporation (IRE) has shown a significant survival benefit for local advanced pancreatic cancer in clinical trials. However, incomplete ablation with local recurrence and major complications limit the potential of this new technology. We have developed an integrated moderate heating electric pulse delivery system which consists of controllable tumor heating, multi-parameter monitoring and electric pulse delivery. The impedance of tumor is greatly decreased after moderate heating at 42°C for 1–2 min, which does not cause any cell death. Moderate heating …

Multivariate Analysis To Identify Potential Biomarkers For Prognosis And Treatment Resistance In Head And Neck Cancer Patients, Christina Ann Wicker

Theses and Dissertations--Toxicology and Cancer Biology

It is estimated that nearly 50,000 individuals in the United States will be diagnosed with head and neck cancer in 2017 (American Cancer Society www.cancer.org). Ninety percent of oral cancers are head and neck squamous cell carcinoma (HNSCC). Major obstacles in the treatment of HNSCC are recurrence and treatment resistance, which contributes to increased mortality. Therefore, there is increased need to determine genetic alterations in HNSCC that may be ideal novel drug targets, and biomarkers to improve diagnostic and prognostic testing.

Abnormal localization and overexpression of base excision repair protein and transcriptional regulator Apurinic/Apyrimidic endonuclease (APE1) has been associated with …

Novel Survivin Inhibitor For Suppressing Pancreatic Cancer Cells Growth Via Downregulating Sp1 And Sp3 Transciption Factors, Myrna Hurtado, Umesh T. Sankpal, Aboubacar Kaba, Shahela Mahammad, Jaya Chhabra, Deondra T. Brown, Raj K. Gurung, Alvin A. Holder, Jamboor K. Vishwanatha, Riyaz Basha

Chemistry & Biochemistry Faculty Publications

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated.

Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression …

Nanopulse Stimulation (Nps) Induces Tumor Ablation And Immunity In Orthotopic 4t1 Mouse Breast Cancer: A Review, Stephen J. Beebe, Brittany P. Lassiter, Siqi Guo

Bioelectrics Publications

Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases …

Cortactin Phosphorylation By Casein Kinase 2 Regulates Actin Related Protein 2/3 Complex Activity And Invadopodia Function, Steven Michael Markwell

Graduate Theses, Dissertations, and Problem Reports (ETD)

Malregulation of the actin cytoskeleton enhances tumor cell motility and invasion. The actin-binding protein cortactin facilitates branched actin network formation through activation of the actin-related protein (Arp) 2/3 complex. Arp2/3 complex activation is responsible for driving increased migration and extracellular matrix (ECM) degradation by governing invadopodia formation and activity. While cortactin-mediated activation of Arp2/3 complex and invadopodia regulation has been well established, signaling pathways responsible for governing cortactin binding to Arp2/3 are unknown. In this dissertation we identify casein kinase (CK) 2α phosphorylation of cortactin as a negative regulator of Arp2/3 binding. CK2α directly phosphorylates cortactin at a conserved threonine …

Nanoparticle Orientation To Control Rna Loading And Ligand Display On Extracellular Vesicles For Cancer Regression, Fengmei Pi, Daniel W. Binzel, Tae Jin Lee, Zhefeng Li, Meiyan Sun, Piotr G. Rychahou, Hui Li, Farzin Haque, Shaoying Wang, Carlo M. Croce, Bin Guo, B. Mark Evers, Peixuan Guo

Markey Cancer Center Faculty Publications

Nanotechnology offers many benefits, and here we report an advantage of applying RNA nanotechnology for directional control. The orientation of arrow-shaped RNA was altered to control ligand display on extracellular vesicle membranes for specific cell targeting, or to regulate intracellular trafficking of small interfering RNA (siRNA) or microRNA (miRNA). Placing membrane-anchoring cholesterol at the tail of the arrow results in display of RNA aptamer or folate on the outer surface of the extracellular vesicle. In contrast, placing the cholesterol at the arrowhead results in partial loading of RNA nanoparticles into the extracellular vesicles. Taking advantage of the RNA ligand for …

Alternative Splicing Of Cytoplasmic Polyadenylation Element Binding Protein 2 Is Modulated Via Serine Arginine Splicing Factor 3 In Cancer Metastasis, James T. Deligio, James Thomas Deligio

Theses and Dissertations

Our laboratory delineated a role for alternative pre-mRNA splicing (AS) in triple negative breast cancer (TNBC). We found the translational regulator cytosolic polyadenylation element binding protein 2 (CPEB2) which has two isoforms, CPEB2A and CPEB2B, is alternatively spliced during acquisition of anoikis resistance (AnR) and metastasis. The splicing event which determines the CPEB2 isoform is via inclusion/ exclusion of exon four in the mature mRNA transcript. The loss of CPEB2A with a concomitant increase in CPEB2B is required for TNBC cells to metastasize in vivo. We examined RNAseq profiles of TNBC cells which had CPEB2 isoforms specifically downregulated to …

Evaluation And Adaptation Of Live-Cell Interferometry For Applications In Basic, Translational, And Clinical Research, Kevin A. Leslie

Theses and Dissertations

Cell mass is an important indicator of cell health and status. A diverse set of techniques have been developed to precisely measure the masses of single cells, with varying degrees of technical complexity and throughput. Here, the development of a non-invasive, label-free optical technique, termed Live-Cell Interferometry (LCI), is described. Several applications are presented, including an evaluation of LCI’s utility for assessing drug response heterogeneity in patient-derived melanoma lines and the measurement of CD3+ T cell kinetics during hematopoietic stem cell transplantation. The characterization of mast cells during degranulation, the measurement of viral reactivation kinetics in Kaposi’s Sarcoma, and drug …

Nuclear Spindles Pave The Way To Metastasis, Patrick J. Hensley, Natasha Kyprianou

Urology Faculty Publications

No abstract provided.

Metabolic Dysregulation And Cancer Mortality In A National Cohort Of Blacks And Whites, Tomi Akinyemiju, Justin Xavier Moore, Suzanne Judd, Susan Lakoski, Michael Goodman, Monika M. Safford, Maria Pisu

Epidemiology and Environmental Health Faculty Publications

Background: We examined the association between metabolic dysregulation and cancer mortality in a prospective cohort of Black and White adults.

Methods: A total of 25,038 Black and White adults were included in the analysis. Metabolic dysregulation was defined in two ways: 1) using the joint harmonized criteria for metabolic syndrome (MetS) and 2) based on factor analysis of 15 variables characterizing metabolic dysregulation. We estimated hazards ratios (HRs) and 95% confidence intervals (CIs) for the association of MetS and metabolic dysregulation with cancer mortality during follow-up using Cox proportional hazards models.

Results: About 46% of Black and 39% of White …

9-Aminoacridine Inhibits Ribosome Biogenesis And Synergizes With Cytotoxic Drugs To Induce Selective Killing Of P53-Deficient Cells, Leonid Anikin, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Common cancer treatments target rapidly dividing cells and do not discriminate between cancer and normal host cells. One approach to mitigating negative side‐effects of cancer treatment is to temporarily arrest cell cycle progression and thus protect normal cells during cytotoxic treatments, a concept called cyclotherapy. We recently proposed that transient inhibition of post‐transcriptional steps of ribosome biogenesis (RBG) can be used to selectively arrest p53‐positive host cells and not p53‐null cancer cells. In this study, we investigated whether cytoprotective RBG inhibition can be achieved through small molecule treatment.

Targeting Ribosome Assembly Factors Selectively Protects P53 Positive Cells From Chemotherapeutic Agents, Russell T. Sapio, Anastasiya Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J. Manna, N. Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Many chemotherapeutic agents act in a nondiscriminatory fashion, targeting both cancerous and noncancerous cells in Sphase and Mphase. One approach to reduce the toxic side effects in normal tissue is to exploit the differences in p53 functionality between cancerous and noncancerous cells. For example, activating p53 signaling by nongenotoxic means can transiently arrest noncancerous p53 positive cells in G1 phase and protect them from the cytotoxic effects of chemotherapeutic drugs. However, since most cancerous cells have faulty p53 signaling, they will proceed to cycle, and continue to be affected by the drug. In this study we asked if this G1‐phase …

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity …

Identifying The Role Of Janus Kinase 1 In Mammary Gland Development And Breast Cancer, Barbara Swenson

Theses & Dissertations

The development of the postnatal mammary gland is tightly controlled by peptide hormones and cytokines. The signaling of these extracellular ligands through their corresponding receptors rely on Janus Kinases (JAKs) that activate downstream Signal Transducers and Activators of Transcription (STATs). The JAK/STAT signaling pathway is crucial for processes such as growth, proliferation, and cell survival of the epithelial tissue, but also for the breakdown and remodeling of the mammary gland via IL-6 class inflammatory cytokines (e.g. LIF and OSM). JAK1 and JAK2, which are expressed in the mammary gland, are thought to have redundant functions. However, our previous studies demonstrated …

Ecog-Acrin (E4805) Randomized Phase Ii Study To Determine The Effect Of 2 Different Doses Of Aflibercept In Patients With Metastatic Renal Cell Carcinoma, Roberto Pili, Opeyemi Jegede, Michael A. Carducci, Judith Manola, David L. Groteluschen, Leonard L. Appleman, Glenn Liu, James C. Shanks, Shaker R. Dakhil, Janice Dutcher, Robert S. Dipaola

Internal Medicine Faculty Publications

Background—Aflibercept is a recombinantly-produced fusion protein that has potent anti-VEGF activity. We tested whether aflibercept has clinical activity in clear cell renal cell carcinoma (ccRCC). The recommended Phase 2 dose was 4 mg/kg but several patients treated at 1 mg/kg demonstrated prolonged progression-free survival (PFS). We therefore tested both doses in a parallel group randomized trial.

Methods—Eligible patients (pts) had histologically confirmed advanced or metastatic ccRCC and previous treatments including prior exposure to a VEGF RTKI. Patients received aflibercept (either 1 mg/kg or 4 mg/kg) day 1 of a 14-day cycle until progression. Patients randomized to 1 mg/kg …

Combinational Sirna Delivery Using Hyaluronic Acid Modified Amphiphilic Polyplexes Against Cell Cycle And Phosphatase Proteins To Inhibit Growth And Migration Of Triple-Negative Breast Cancer Cells, Manoj B. Parmar, Daniel Nisakar Meenakshi Sundaram, Remant Bahadur Kc, Robert Maranchuk, Hamidreza Montazeri Aliabadi, Judith C. Hugh, Raimar Löbenberg, Hasan Uludağ

Pharmacy Faculty Articles and Research

Triple-negative breast cancer is an aggressive form of breast cancer with few therapeutic options if it recurs after adjuvant chemotherapy. RNA interference could be an alternative therapy for metastatic breast cancer, where small interfering RNA (siRNA) can silence the expression of aberrant genes critical for growth and migration of malignant cells. Here, we formulated a siRNA delivery system using lipid-substituted polyethylenimine (PEI) and hyaluronic acid (HA), and characterized the size, ζ-potential and cellular uptake of the nanoparticulate delivery system. Higher cellular uptake of siRNA by the tailored PEI/HA formulation suggested better interaction of complexes with breast cancer cells due to …

The Role Of Talin2 In Breast Cancer Tumorigenesis And Metastasis, Liqing Li, Xiang Li, Lei Qi, Piotr G. Rychahou, Naser Jafari, Cai Huang

Markey Cancer Center Faculty Publications

Recent studies show that talin2 has a higher affinity to β-integrin tails and is indispensable for traction force generation and cell invasion. However, its roles in cell migration, cancer cell metastasis and tumorigenesis remain to be determined. Here, we used MDA-MB-231 human breast cancer cells as a model to define the roles of talin2 in cell migration, invasion, metastasis and tumorigenesis. We show here that talin2 knockdown (KD) inhibited cell migration and focal adhesion dynamics, a key step in cell migration, and that talin2 knockout (KO) inhibited cell invasion and traction force generation, the latter is crucial for cell invasion. …

Development Of Halofluorochromic Polymer Nanoassemblies For The Potential Detection Of Liver Metastatic Colorectal Cancer Tumors Using Experimental And Computational Approaches, Derek Alexander Reichel, Louis T. Curtis, Elizabeth Ehlman, B. Mark Evers, Piotr G. Rychahou, Hermann B. Frieboes, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Purpose—To develop polymer nanoassemblies (PNAs) modified with halofluorochromic dyes to allow for the detection of liver metastatic colorectal cancer (CRC) to improve therapeutic outcomes.

Methods—We combine experimental and computational approaches to evaluate macroscopic and microscopic PNA distributions in patient-derived xenograft primary and orthotropic liver metastatic CRC tumors. Halofluorochromic and non-halofluorochromic PNAs (hfPNAs and n-hfPNAs) were prepared from poly(ethylene glycol), fluorescent dyes (Nile blue, Alexa546, and IR820), and hydrophobic groups (palmitate), all of which were covalently tethered to a cationic polymer scaffold [poly(ethylene imine) or poly(lysine)] forming particles with an average diameter < 30 nm.

Results—Dye-conjugated PNAs showed no aggregation under …