Medicine and Health Sciences Commons^™

Social Determinants Of Health And Lung Cancer Surgery: A Qualitative Study, Dede K. Teteh, Betty Ferrell, Oluwatimilehin Okunowo, Aidea Downie, Loretta Erhunmwunsee, Susanne B. Montgomery, Dan J. Raz, Rick Kittles, Jae Y. Kim, Virginia Sun

Health Sciences and Kinesiology Faculty Articles

Introduction: Social determinants of health (SDOH) are non-clinical factors that may affect the outcomes of cancer patients. The purpose of this study was to describe the influence of SDOH factors on quality of life (QOL)-related outcomes for lung cancer surgery patients.

Methods: Thirteen patients enrolled in a randomized trial of a dyadic self-management intervention were invited and agreed to participate in semi-structured key informant interviews at study completion (3 months post-discharge). A conventional content analysis approach was used to identify codes and themes that were derived from the interviews. Independent investigators coded the qualitative data, which were subsequently …

Modified Linear Peptides Effectively Silence Stat-3 In Breast Cancer And Ovarian Cancer Cell Lines, Dindyal Mandal, Sandeep Lohan, Muhammad Imran Sajid, Abdulelah Alhazza, Rakesh Kumar Tiwari, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

RNA interference (RNAi) has drawn enormous attention as a powerful tool because of its capability to interfere with mRNA and protein production. However, designing a safe and efficient delivery system in RNAi therapeutics remains challenging. Herein, we have designed and synthesized several linear peptides containing tryptophan (W) and arginine (R) residues separated by the β-alanine (βA) spacer and attached to a lipophilic fatty acyl chain, cholesterol, or PEG. The peptide backbone sequences were: Ac-C-βA-βA-W4-βA-βA-R4-CO-NH2 and Ac-K-βA-βA-W4-βA-βA-R4-CO-NH2, with only a difference in N-terminal amino acid. The cysteine side chain in the first sequence was used for the conjugation with PEG2000 and …

Design And Application Of Hybrid Cyclic-Linear Peptide-Doxorubicin Conjugates As A Strategy To Overcome Doxorubicin Resistance And Toxicity, Saghar Mozaffari, David Salehi, Parvin Mahdipoor, Richard Beuttler, Rakesh Tiwari, Hamidreza Montazeri Aliabadi, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is used for breast cancer, leukemia, and lymphoma treatment as an effective chemotherapeutic agent. However, Dox use is restricted due to inherent and acquired resistance and an 8-fold increase in the risk of potentially fatal cardiotoxicity. Hybrid cyclic-linear peptide [R5K]W7A and linear peptide R5KW7A were conjugated with Dox through a glutarate linker to afford [R5K]W7A-Dox and R5KW7A-Dox conjugates to generate Dox derivatives. Alternatively, [R5K]W7C was conjugated with Dox via a disulfide linker to generate [R5K]W7C–S–S-Dox conjugate, where S–S is a disulfide bond. Comparative antiproliferative assays between conjugates [R5K]W7A-Dox, [R5K]W7C–S–S-Dox, linear R5KW7A-Dox, the corresponding physical mixtures of the peptides, …

Human Oncoprotein 5mp Suppresses General And Repeat-Associated Non-Aug Translation Via Eif3 By A Common Mechanism, Chingakham Ranjit Singh, M. Rebecca Glineburg, Chelsea Moore, Naoki Tani, Rahul Jaiswal, Ye Zou, Eric Aube, Sarah Gillaspie, Mackenzie Thornton, Ariana Cecil, Madelyn Hilgers, Azuma Takasu, Izumi Asano, Masayo Asano, Carlos R. Escalante, Akira Nakamura, Peter K. Todd, Katsura Asano

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

eIF5-mimic protein (5MP) is a translational regulatory protein that binds the small ribosomal subunit and modulates its activity. 5MP is proposed to reprogram non-AUG translation rates for oncogenes in cancer, but its role in controlling non-AUG initiated synthesis of deleterious repeat-peptide products, such as FMRpolyG observed in fragile-X-associated tremor ataxia syndrome (FXTAS), is unknown. Here, we show that 5MP can suppress both general and repeat-associated non-AUG (RAN) translation by a common mechanism in a manner dependent on its interaction with eIF3. Essentially, 5MP displaces eIF5 through the eIF3c subunit within the preinitiation complex (PIC), thereby increasing the accuracy of initiation. …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

A Global Review On Short Peptides: Frontiers And Perspectives, Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Sherif Elnagdy, Krzysztof Kaczmarek, John Matsoukas, Roger New, Keykavous Parang, Octavio Paredes Lopez, Hamideh Parhiz, Conrad O. Perera, Monica Pickholz, Milan Remko, Michele Saviano, Mariusz Skwarczynski, Yefeng Tang, Wojciech M. Wolf, Taku Yoshiya, Janusz Zabrocki, Piotr Zielenkiewicz, Maha Alkhazindar, Vanessa Barriga, Konstantinos Kelaidonis, Elham Mousavinezhad Sarasia, Istvan Toth

Pharmacy Faculty Articles and Research

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. …

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

Rapamycin Treatment Correlates Changes In Primary Cilia Expression With Cell Cycle Regulation In Epithelial Cells, Maha Jamal, Ane C.F. Nunes, Nosratola D. Vaziri, Ramani Ramchandran, Robert L. Bacallao, Andromeda M. Nauli, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are sensory organelles that regulate cell cycle and signaling pathways. In addition to its association with cancer, dysfunction of primary cilia is responsible for the pathogenesis of polycystic kidney disease (PKD) and other ciliopathies. Because the association between cilia formation or length and cell cycle or division is poorly understood, we here evaluated their correlation in this study. Using Spectral Karyotyping (SKY) technique, we showed that PKD and the cancer/tumorigenic epithelial cells PC3, DU145, and NL20-TA were associated with abnormal ploidy. We also showed that PKD and the cancer epithelia were highly proliferative. Importantly, the cancer epithelial cells …

“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 …

Emotion Regulation And Positive Affect In The Context Of Salivary Alpha-Amylase Response To Pain In Children With Cancer, Brooke N. Jenkins, Douglas A. Granger, Ryan J. Roemer, Ariana Martinez, Tara K. Torres, Michelle A. Fortier

Psychology Faculty Articles and Research

Background

Children with cancer routinely undergo painful medical procedures invoking strong physiological stress responses. Resilience to this pain may be conferred through resources such as emotion regulation strategies and positive affect.

Procedure

This study measured dispositional positive affect in children with cancer (N = 73) and randomly assigned participants to one of three emotion regulation strategy conditions (distraction, reappraisal, or reassurance). Children applied their assigned strategy during an experimental pain procedure (the cold pressor task [CPT]) and provided saliva samples before, immediately after, and 15 min after the CPT. Saliva samples were later assayed for salivary alpha amylase (sAA)—a surrogate …

The Costs Of Cancer, Jamie Mosely

Honors Papers and Posters

This poster explores the relationship between more advanced cancer-fighting technologies and the increase in healthcare costs over the last several decades, and the socioeconomic impact this has for patients with less disposable income or no health insurance.

Novel Ph-Sensitive Cyclic Peptides, Dhammika Weerakkody, Anna Moshnikova, Naglaa Salem El-Sayed, Ramona-Cosima Adochite, Gregory Slaybaugh, Jovana Golijanin, Rakesh Tiwari, Oleg A. Andreev, Keykavous Parang, Yana K. Reshetnyak

Pharmacy Faculty Articles and Research

A series of cyclic peptides containing a number of tryptophan (W) and glutamic acid (E) residues were synthesized and evaluated as pH-sensitive agents for targeting of acidic tissue and pH-dependent cytoplasmic delivery of molecules. Biophysical studies revealed the molecular mechanism of peptides action and localization within the lipid bilayer of the membrane at high and low pHs. The symmetric, c[(WE)4WC], and asymmetric, c[E4W5C], cyclic peptides translocated amanitin, a polar cargo molecule of similar size, across the lipid bilayer and induced cell death in a pH- and concentration-dependent manner. Fluorescently-labelled peptides were evaluated for targeting of acidic 4T1 mammary tumors in …

Real-Time Detection Of Breast Cancer Cells Using Peptidefunctionalized Microcantilever Arrays, Hashem Etayash, Keren Jiang, Sarfuddin Azmi, Thomas Thundat, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Ligand-directed targeting and capturing of cancer cells is a new approach for detecting circulating tumor cells (CTCs). Ligands such as antibodies have been successfully used for capturing cancer cells and an antibody based system (CellSearch®) is currently used clinically to enumerate CTCs. Here we report the use of a peptide moiety in conjunction with a microcantilever array system to selectively detect CTCs resulting from cancer, specifically breast cancer. A sensing microcantilever, functionalized with a breast cancer specific peptide 18-4 (WxEAAYQrFL), showed significant deflection on cancer cell (MCF7 and MDA-MB-231) binding compared to when exposed to noncancerous (MCF10A and HUVEC) cells. …

Analyzation Of Metabolic Reprogramming In Drug-Resistant Mcf-7 Cells, Derick Han, Ho Leung, Andrew Vo

Student Scholar Symposium Abstracts and Posters

The Warburg effect states that cancer cells mainly receive their energy from anaerobic glycolysis. Thus, mitochondria play a different role in the metabolism of cancer cells as opposed to normal, healthy cells. In chemotherapy, there is always a chance of the cancer regressing. Making drug-resistant cancer cells to analyze their metabolism may change how cancer is treated. This study aimed to create drug-resistant MCF-7 cell lines with doxorubicin in order to determine the metabolic changes that have occurred in the process of becoming resistant to drug treatments.

Clinical Applications Of A Combination Chemotherapy Using 8-Chloro Camp And 8-Chloro Adenosine, Erik Munoz, Andrea Saich, Andrew Cox, Yu-An Peter Chang

Student Scholar Symposium Abstracts and Posters

Dr. Cho-Chung from the NIH first thought to use halogenated cAMP derivatives as competitive inhibitors of cAMP to slow down cancer cell mitosis. While the iodine and bromine substituted versions showed very little therapeutic actions, 8-Chloro cAMP has been shown to have strong anti-cancer effects. This has been shown in the phase II clinical trials this drug has undergone. However, these trials have had issues with solubility and toxicity. The drug is similar to vitamin C and is excreted quickly. Scientists tried to overcome this by using a peristaltic pump to give patients a continuous dosage, but this proved too …

Drug-Induced Cardiotoxicity Of Oncological Agents: Monitoring Parameters, Prevention, And Future Chemotherapy, Sarah Nguyen, Mary Nguyen, Laura Tsu

Pharmacy Faculty Articles and Research

The goal of this article is to educate pharmacists of the impact of cardiotoxicity on chemotherapy regimens including key cancer agents, monitoring parameters, prevention, and the future of chemotherapy.

Assessment Of The Effects Of Caffeine, Gallic Acid, And Epigallocatechin-3-Gallate On Cell Inhibition, Pim-3 And E. Cadherin Protein Levels In Two Lines Of Pancreatic Cancer Cells, Lena Haddad, Melissa Rowland-Goldsmith

Student Scholar Symposium Abstracts and Posters

According to the American Cancer Society, pancreatic cancer is currently the fourth leading cause of cancer related deaths in the United States. In addition to being an exceptionally aggressive form of cancer, it is particularly difficult to treat because it is usually diagnosed in late stages after the onset of metastasis (1). Consequently, the current treatments used, including chemotherapy and radiation, have been rendered ineffective (2). As a result, focus has been placed on using dietary alternatives which are known to possess chemopreventive properties (3). Previous studies have indicated that Gallic acid (an important phytochemical in pomegranates) and Epigallocatechin-3-Gallate (the …

Synthesis And Evaluation Of Antiproliferative Activity Of Substituted N-(9-Oxo-9h-Xanthen-4-Yl)Benzenesulfonamides, Somayeh Motavallizadeh, Asal Fallah-Tafti, Saeedeh Maleki, Amir Nasrolahi Shirazi, Mahboobeh Pordeli, Maliheh Safavi, Sussan Kabudanian Ardestani, Shaaban Asd, Rakesh Tiwari, Donghoon Oh, Abbas Shafiee, Alireza Foroumadi, Keykavous Parang, Tahmineh Akbarzadeh

Pharmacy Faculty Articles and Research

Several novel N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamides derivatives were prepared as potential antiproliferative agents. The in vitro antiproliferative activity of the synthesized compounds was investigated against a panel of tumor cell lines including breast cancer cell lines (MDA-MB-231, T-47D) and neuroblastoma cell line (SK-N-MC) using MTT colorimetric assay. Etoposide, a well-known anticancer drug, was used as a positive standard drug. Among synthesized compounds, 4-methoxy-N-(9-oxo-9H-xanthen-4-yl)benzenesulfonamide (5i) showed the highest antiproliferative activity against MDA-MB-231, T-47D, and SK-N-MC cells. Furthermore, pentafluoro derivatives 5a and 6a exhibited higher antiproliferative activity than doxorubicin against human leukemia cell line (CCRF-CEM) and breast adenocarcinoma (MDAMB- 468) cells. Structure-activity relationship studies revealed …

3-Substitued Indoles: One Pot Synthesis And Evaluation Of Anticancer And Src Kinase Inhibitory Activities, V. Kameshwara Rao, Bhupender S. Chhikara, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

An efficient and economical method was developed for the synthesis of 3-substituted indoles by one pot three-component coupling reaction of a substituted or unsubstituted benzaldehyde, N-methylaniline, and indole or N-methylindole using Yb(OTf)3-SiO2 as a catalyst. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. The 4-methylphenyl (4o and 4p) and 4-methoxyphenyl (4q) indole derivatives inhibited the cell proliferation of SK-OV-3 and HT-29 cells by 7077% at a concentration of 50 μM. The unsubstituted phenyl (4d) and 3-nitrophenyl (4l) derivatives showed the inhibition of c-Src kinase …

Modeling Measurement Error In Tumor Characterization Studies, Cyril Rakovski, Daniel J. Weisenberger, Paul Marjoram, Peter W. Laird, Kimberly D. Siegmund

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background: Etiologic studies of cancer increasingly use molecular features such as gene expression, DNA methylation and sequence mutation to subclassify the cancer type. In large population-based studies, the tumor tissues available for study are archival specimens that provide variable amounts of amplifiable DNA for molecular analysis. As molecular features measured from small amounts of tumor DNA are inherently noisy, we propose a novel approach to improve statistical efficiency when comparing groups of samples. We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon …

Outpatient Administration Of Paclitaxel, Siu Fun Wong

Pharmacy Faculty Articles and Research

Paclitaxel (Taxol®, Bristol-Meyers Squibb), anti neoplastic agent made from the bark of the Pacific yew tree, is undoubtedly one of the most exciting agents to be evaluated over the past decade. Paclitaxel has demonstrated significant promise against ovarian and metastatic breast cancer, and appears to be the most effective single agent to date for non-small-cell lung cancer in trials conducted by Eastern Cooperative Oncology Group (ECOG).