Pharmacy and Pharmaceutical Sciences Commons^™

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Modulation Of Hypoxia-Induced Chemoresistance To Polymeric Micellar Cisplatin: The Effect Of Ligand Modification Of Micellar Carrier Versus Inhibition Of The Mediators Of Drug Resistance, Hoda Soleymani Abyaneh, Amir Hassan Soleimani, Mohammad Reza Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(-carboxyl-"-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and …

Astromimetics: The Dawn Of A New Era For (Bio)Materials Science?, Vuk Uskoković, Victoria M. Wu

Pharmacy Faculty Articles and Research

Composite, multifunctional fine particles are likely to be at the frontier of materials science in the foreseeable future. Here we present a submicron composite particle that mimics the stratified structure of the Earth by having a zero-valent iron core, a silicate/silicide mantle, and a thin carbonaceous crust resembling the biosphere and its biotic deposits. Particles were formulated in a stable colloidal form and made to interact with various types of healthy and cancer cells in vitro. A selective anticancer activity was observed, promising from the point of view of the intended use of the particles for tumor targeting across the …

“Do We Know Jack” About Jak? A Closer Look At Jak/Stat Signaling Pathway, Emira Bousoik, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Janus tyrosine kinase (JAK) family of proteins have been identified as crucial proteins in signal transduction initiated by a wide range of membrane receptors. Among the proteins in this family JAK2 has been associated with important downstream proteins, including signal transducers and activators of transcription (STATs), which in turn regulate the expression of a variety of proteins involved in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis plays a major role in the proliferation and survival of different cancer cells, and may even be involved in resistance mechanisms against molecularly targeted drugs. Despite extensive research focused on the …

Olanzapine For Chemotherapy-Induced Nausea And Vomiting, John B. Bossaer

John B. Bossaer

Excerpt: Navari and colleagues (July 14 issue)1 report on the use of olanzapine for the prevention of chemotherapy-induced nausea and vomiting.

'No Pink Ribbons': How Women's Lived Experiences With Breast Atypia Inform Decisions Involving Risk-Reducing Medications, Sarah L. Goff, Reva Kleppel, Grace Makari-Judson

Journal of Patient-Centered Research and Reviews

Purpose: Atypical hyperplasia (AH) is associated with a nearly 4-fold elevation of lifetime risk for breast cancer, and lobular carcinoma in situ (LCIS) is associated with a 7- to 8-fold risk. Women with AH/LCIS make numerous decisions in the course of treatment, including whether to take a risk-reducing medication, an option relatively few women pursue. We explored women’s decision-making processes through patient narratives in an effort to inform decision supports for AH/LCIS.

Methods: We conducted in-depth interviews with 20 English-speaking women with AH/LCIS and no subsequent diagnosis of invasive breast cancer who had enrolled in the Rays of Hope Center …

Therapeutic Challenge With A Cdk 4/6 Inhibitor Induces An Rb-Dependent Smac-Mediated Apoptotic Response In Non-Small Cell Lung Cancer., Thangavel Chellappagounder, Boopathi Ettickan, Yi Liu, Christopher Mcnair, Alex Haber, Maryna Perepelyuk, Anshul Bhardwaj, Sankar Addya, Adam Ertel, Sunday Shoyele, Ruth Birbe, Joseph M. Salvino, Adam P. Dicker, Karen E. Knudsen, Robert B. Den

Department of Radiation Oncology Faculty Papers

Purpose: The retinoblastoma tumor suppressor (RB), a key regulator of cell-cycle progression and proliferation, is functionally suppressed in up to 50% of non-small cell lung cancer (NSCLC). RB function is exquisitely controlled by a series of proteins, including the CyclinD-CDK4/6 complex. In this study, we interrogated the capacity of a CDK4/6 inhibitor, palbociclib, to activate RB function.

Experimental Design and Results: We employed multiple isogenic RB-proficient and -deficient NSCLC lines to interrogate the cytostatic and cytotoxic capacity of CDK 4/6 inhibition in vitro and in vivo We demonstrate that while short-term exposure to palbociclib induces cellular senescence, prolonged exposure results …

Risk Stratification For Bleeding Complications In Patients With Venous Thromboembolism: Application Of The Has-Bled Bleeding Score During The First 6 Months Of Anticoagulant Treatment, Joshua D. Brown, Amie J. Goodin, Gregory Y. H. Lip, Val R. Adams

Pharmacy Practice and Science Faculty Publications

Background—The Hypertension, Abnormal renal/liver function, Stroke, Bleeding, Labile International Normalized Ratio (INR), Elderly, Drugs or alcohol use (HAS-BLED) score has strong predictive validity for major bleeding complications, but limited validation has been conducted in venous thromboembolism (VTE). This study evaluates the HAS-BLED score in a large cohort of VTE patients.

Methods and Results—A retrospective cohort of adults ≥ 18 years with primary diagnosis of VTE between January 1, 2010 and November 31, 2013 were identified in an insurance claims database. Patients were tracked until death, any bleed event, or end of study period. HAS-BLED score and components were …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …

Evaluation Of A Drug Delivery System Based On Cyclodextrins For Cancer Therapy, Caroline Mendes

Doctoral

Due to the side-effects caused by regular chemotherapy, the development of drug delivery systems that can specifically target cancer cells and deliver the therapeutic dose is required. In this study, a folate-derivative of β-cyclodextrin has been studied as a vehicle for targeting folate receptors (FR) and delivering the chemotherapeutic drug methotrexate (MTX). FRs can be considered key cell membrane targets since they are commonly over-expressed in cancer cells and play an important role in cancer development and progression. Cyclodextrins (CDs) are cyclic oligosaccharides with a unique structure that allows them to form inclusion complexes with guest molecules, increasing their aqueous …

Economic Burden Of Renal Cell Carcinoma (Rcc) And Treatment Patterns, Overall Survival And Healthcare Costs Among Older Metastatic Rcc Patients, Hrishikesh P. Kale

Theses and Dissertations

Background

Renal cell carcinoma (RCC) is the most common type of kidney cancer. Patients diagnosed with metastatic RCC (mRCC) have shorter overall survival compared to those diagnosed at earlier stages. Several targeted therapies, which cost from $7,000 - $16,000 per month have been approved since 2005 to treat mRCC. In addition, there is a growing interest in the use of cytoreductive nephrectomy (CN) with targeted therapies among mRCC patients. However, little is known regarding the economic burden of RCC and role of CN and prescribing patterns of targeted therapies among older mRCC patients.

Objectives

1) To assess the economic burden …