Pharmacy and Pharmaceutical Sciences Commons^™

Developing Curcumin Analogues For Treating Breast Cancer, Tulasi Laxmi Nutalapati

Theses, Dissertations and Capstones

Breast cancer is still one of the most common types of cancer and one of the most common causes of cancer-related deaths in women around the world. Despite significant advances in early detection and treatment strategies, drug resistance, systemic toxicity, and poor outcomes in aggressive subtypes continue to limit the overall effectiveness of cancer therapy. Natural compounds have become promising anticancer agents because they can target many different things and are not very toxic. Curcumin has shown promise as an anticancer drug, but it cannot be used in the clinic because it does not absorb well, breaks down quickly, and …

Dual Role Of Triphala Extracts In Breast Cancer Therapy: Enhanced Paclitaxel Cytotoxicity By Ethanolic Extract And Cytoprotection By Aqueous Extract, Supamas Charucharana, Poonlarp Cheepsunthorn Ph.D., Chalisa L. Cheepsunthorn Ph.D.

Chulalongkorn Medical Journal

Background: Combining antioxidants with chemotherapy is an emerging strategy to reduce chemotoxicity in normal cells. Triphala (TPL), a polyphenol-rich Thai herbal formulation, has shown promise in enhancing chemotherapy efficacy, but its interaction with paclitaxel (PX) in breast cancer treatment remains underexplored.

Objective: This study evaluates the effects of aqueous (TPL-w) and ethanolic (TPL-a) TPL extracts combined with low-dose PX on breast cancer cells and non-tumorigenic mammary epithelial cells.

Methods: The bioactive components of TPL-w and TPL-a were identified using high-performance liquid chromatography (HPLC). Thiazolyl blue tetrazolium bromide (MTT) and chloromethyl 2′,7′-dichlorodihydrofluorescein diacetate (CM-H₂DCFDA) assays assessed cell viability and …

Antioxidant And Chemotherapeutic Synergy: Triphala Enhances Doxorubicin Cytotoxicity In Breast Cancer Cells And Reduces Toxicity In Non-Tumorigenic Cells, Supamas Charucharana, Poonlarp Cheepsunthorn Ph.D., Chalisa Louicharoen Cheepsunthorn Ph.D.

Chulalongkorn Medical Journal

Background: The combining of antioxidants with chemotherapy is increasingly explored to minimize toxicity in non-cancerous cells during breast cancer treatment. Triphala (TPL), a Thai herbal compound rich in antioxidants, shows potential as a complementary candidate for breast cancer chemotherapy.

Objective: This study investigated the combined effects of TPL and low-dose doxorubicin (DOX) on human breast cancer and non-tumorigenic mammary epithelial cells.

Methods: TPL’s bioactive compounds were analyzed via high-performance liquid chromatography (HPLC). Cell viability and reactive oxygen species (ROS) levels were assessed in breast cancer (MDA-MB-231, MCF-7) and epithelial (MCF-10A) cells using thiazolyl blue tetrazolium bromide (MTT) and chloromethyl 2′,7′-dichlorodihydrofluorescein …

Exosomes And Encapsulated Exomirs In Breast Cancer: Theragnostic Applications And Clinical Implications, Muhammad Imran Sajid, Shafia Bukhari, Hamid Ilyas, Rubina Malik, Minahil Fatima, Rakesh Kumar Tiwari, Surya M. Nauli, Khawaja Husnain Haider

Pharmacy Faculty Books and Book Chapters

Exosomes, released by cells, are small vesicles that have emerged as critical theranostic tools in breast cancer due to their unique ability to transport diverse biomolecules such as proteins, lipids, and RNAs, including microRNAs (ExomiRs). These vesicles are critical in modulating the tumor microenvironment, driving processes like cancer proliferation, invasion, metastasis, and drug resistance. Exosomal microRNAs such as ExomiR-21, ExomiR-1246, and ExomiR-155, with their profound influence on the gene expressions in the recipient cells, are the unsung heroes in tumor progression and immune modulation. This chapter delves into exosome's dual diagnostic and therapeutic potential in breast cancer. It highlights their …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

Enhancing The Anticancer Effects Of Apiaceae Spice Phytochemicals., Jared Lee Scott

Electronic Theses and Dissertations

Breast cancer (BC) is a leading contributor to the death of women and is the most common type of cancer. Many chemotherapy drugs are developed from plants, and some plant extracts can exhibit significant anticancer activities while also having less toxic side effects. The Apiaceae plant family consists of several species that are used as culinarily spices which have demonstrated antioxidant, chemopreventive, and anticancer activities. The encapsulation of anticancer phytochemicals into naturally produced membrane-bound nanoparticles known as exosomes could improve their systemic distribution and efficacy. Exosomes are involved in cell-to-cell communication through the delivery of proteins, nucleic acids, and small …

Proteomic Characterization And Cytotoxic Potential Of Proteins From Cuscuta (Cuscuta Epithymum (L.) Crude Herbal Product Against Mcf-7 Human Breast Cancer Cell Line, Umaima Akhtar, Yamna Khurshid, Bishoy El-Aarag, Basir Syed, Ishtiaq A. Khan, Keykavous Parang, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

The burden of breast cancer, the second leading cause of death worldwide, is increasing at an alarming rate. Cuscuta, used in traditional medicine for different ailments, including cancer, is known for containing phytochemicals that exhibit anticancer activity; however, the bioactivities of proteins from this plant remain unexplored. This study aimed to screen the cytotoxic potential of proteins from the crude herbal product of Cuscuta epithymum(L.) (CE) harvested from the host plants Alhagi maurorum and Medicago sativa.

Methods

The proteins from CE were extracted using a salting-out method, followed by fractionation with a gel filtration chromatography column. Gel-free shotgun …

Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells, Emily Esquea, Lorela Ciraku, Riley Young, Jessica Merzy, Alexandra Talarico, Nusaiba Ahmed, Mangalam Karuppiah, Anna Ramesh, Adam Chatoff, Claudia Crispim, Adel Rashad, Simon Cocklin, Nathaniel Snyder, Joris Beld, Nicole Simone, Mauricio Reginato, Alexej Dick

Kimmel Cancer Center Faculty Papers

Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to …

Proteomic Identification Of Hemp (Cannabis Sativa) Seeds By Tandem Mass Spectrometry And Evaluation Of Cytotoxic Activity, Taran Harris

Pharmaceutical Sciences (MS) Theses

Hemp (Cannabis sativa) has a long history of use globally as a source of traditional medicine, spiritual enlightenment, and recreational enjoyment. While it was commonly consumed for both medical and recreational purposes in the United States, it was classified as a Schedule 1 drug in 1937, severely restricting its use and research opportunities. Although hemp itself lacks psychoactive properties, Cannabis sativa flowers contain THC, the compound responsible for its psychotropic effects. This restriction hindered quality research into cannabis and its constituents. The study employed techniques, including top-down proteomics, size exclusion chromatography, affinity chromatography, high-resolution ESI QTOF LC/MS/MS, and …

Harnessing Exosomes As A Platform For Drug Delivery In Breast Cancer: A Systematic Review For In Vivo And In Vitro Studies, Abdulwahab Teflischi Gharavi, Saeed Irian, Azadeh Niknejad, Keykavous Parang, Mona Salimi

Pharmacy Faculty Articles and Research

Breast cancer remains a significant global health concern, emphasizing the critical need for effective treatment strategies, especially targeted therapies. This systematic review summarizes the findings from in vitro and in vivo studies regarding the therapeutic potential of exosomes as drug delivery platforms in the field of breast cancer treatment. A comprehensive search was conducted across bibliographic datasets, including Web of Science, PubMed, and Scopus, using relevant queries from several related published articles and the Medical Subject Headings Database. Then, all morphological, biomechanical, histopathological, and cellular-molecular outcomes were systematically collected. A total of 30 studies were identified based on the Preferred …

Targeting Strategies To Optimize The Therapeutic Potential Of Gold Compounds Against Her2-Positive Breast Cancers, Afruja Ahad

Dissertations, Theses, and Capstone Projects

The overexpression of HER2 accounts for 20-30% of breast cancer tumors and not only serves as a marker for poor predictive clinical outcomes but also as a target for treatment. Antibody-drug conjugates (ADCs) combine the selectivity of monoclonal antibodies (mAbs) with the efficacy of chemotherapeutic drugs to provide targeted treatment without toxicity to normal tissue. Most of the ADCs currently in the clinic for cancer chemotherapy are based on complex organic molecules. In contrast, the conjugation of metallodrugs to mAbs has been overlooked when there is enormous potential in this area with the resurgence of metal-based drugs as prospective cancer …

Development And Evaluation Of A Nanofiber Membrane In Vitro As A Therapeutic Alternative For The Post Treatment In Breast Cancer Cell In A Murine Model, Bruno A. Valades-Aguilar, Diana Ginette Zarate-Triviño, José Raúl Rángel-López, Moises Armides Franco-Molina, Jorge Luis Menchaca-Arredondo, María Cristina Rodríguez-Padilla

Research Symposium

Worldwide female breast cancer is the most commonly diagnosed cancer, with an estimated 2.3 million new cases in 2020, reason for the need of targeted therapies that can maximize treatment success and minimize toxicity. Nanoparticles of gold (AuNps) exhibit cytotoxic properties against certain types of cancer cell lines. Nanofibers have been use in the drug delivery systems due to its degradability and high surface area. We proposed a membrane with nanometric fibers using polivinilic alcohol (PVA) and chitosan (Qts) loaded with AuNps and Doxorubicin (Doxo) with the purpose of diminish tumor regression.

PVA-Qts membrane was develop with electrospinning, the injection, …

Targeting Breast Cancer: The Familiar, The Emerging, And The Uncharted Territories, Hamidreza Montazeri Aliabadi, Arthur Manda, Riya Sidgal, Co Chung

Pharmacy Faculty Articles and Research

Breast cancer became the most diagnosed cancer in the world in 2020. Chemotherapy is still the leading clinical strategy in breast cancer treatment, followed by hormone therapy (mostly used in hormone receptor-positive types). However, with our ever-expanding knowledge of signaling pathways in cancer biology, new molecular targets are identified for potential novel molecularly targeted drugs in breast cancer treatment. While this has resulted in the approval of a few molecularly targeted drugs by the FDA (including drugs targeting immune checkpoints), a wide array of signaling pathways seem to be still underexplored. Also, while combinatorial treatments have become common practice in …

Isolation And Total Synthesis Of Sigma-2 Ligands From Marine Cyanobacteria, Andrea Hough

Electronic Theses and Dissertations

Cyanobacteria have been studied for over 50 years as a source of new antibiotics, antiviral, and anticancer drugs. The research described in this dissertation investigates marine cyanobacteria as a source of natural products with activity within the central nervous system and with cytotoxicity against breast cancer cells. Barbamide (1) is a known cyanobacterial metabolite that has been re-isolated from a variety of species and collection sites suggesting broad utility as a signaling molecule. Utilizing the psychoactive drug screening program, we screened barbamide for CNS activity and found that barbamide exhibited affinity for the kappa opioid receptor (KOR) and …

The Mechanism Of Pda-Peg/Copper Selectively Killing Cancer Cells And Its Application In Treating Triple-Negative Breast Cancer And Advanced Ovarian Cancer, Xiangxiang Hu

Theses and Dissertations

Cancer is one of the leading modality diseases. The number of cancer patients has increased in the last decades due to radiation, aging, stress condition, and other reasons. There are three traditional cancer therapies (radiation therapy, chemotherapy, and surgery). Even though these treatments improve the life span of cancer patients, many cancer patients still lost their lives due to the development of tolerance. Thus, it is urgent to develop new kinds of treatments to extend the life span of patients. In recent decades, nanomedicine, which utilizes nanotechnology to deliver chemotherapy agents into tumor sites and improve the anticancer effect and …

Synthesis Of Tert-Butyl Ester And Ethyl Ester Prodrugs Of L-Gamma-Methyleneglutamic Acid Amides For The Treatment Of Cancer, Tristan D. Tran

Honors Theses

Metabolic pathways differ in cancer cells compared to noncancerous cells. Glutaminolysis is the primary producer of biosynthetic precursors in cancer cells, which allows for the cells to proliferate. In previous publications, the Le lab has established efficient synthetic routes to L-γ-methyleneglutamic acid amides which have shown to be as efficacious as tamoxifen and olaparib in inhibiting the growth of various breast cancer cell lines. These compounds have shown to inhibit the growth of MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cell lines after 24 or 72 h of exposure. Furthermore, these compounds were selective in inhibiting the growth of cancer …

Phytochemical Analysis, Antioxidant And Anticancer Effects Of Clitoria Ternatae Extract On Breast T47d Cancer Cells, Ade Arsianti, Shahjahan Pasha Mahindra, Norma Nur Azizah, Ajeng Megawati Fajrin, Lince Dameria Nadapdap

Indonesian Journal of Medical Chemistry and Bioinformatics

Background: Breast cancer is one of the most common and deadly forms of cancer in the world. Cancer is a multi-factorial disease. Genetic factors, environment and lifestyle have a role in the development of cancer. One of the mechanisms of cancer development is when an imbalance between free radicals and antioxidants in the human body occurs. Uncontrolled and excessive amount of free radicals and cause cell damage and uncontrolled cell growth. Clitoria ternate is a plant that is often found in Asia and many of the benefits of this flower have been studied. This study aims to determine the phytochemical …

A Therapeutic Sheep In Metastatic Wolf's Clothing: Trojan Horse Approach For Cancer Brain Metastases Treatment, Hai-Jun Liu, Mingming Wang, Shanshan Shi, Xiangxiang Hu, Peisheng Xu

Faculty Publications

Early-stage brain metastasis of breast cancer (BMBC), due to the existence of an intact blood–brain barrier (BBB), is one of the deadliest neurologic complications. To improve the efficacy of chemotherapy for BMBC, a Trojan horse strategy-based nanocarrier has been developed by integrating the cell membrane of a brain-homing cancer cell and a polymeric drug depot. With the camouflage of a MDA-MB-231/Br cell membrane, doxorubicin-loaded poly (D, L-lactic-co-glycolic acid) nanoparticle (DOX-PLGA@CM) shows enhanced cellular uptake and boosted killing potency for MDA-MB-231/Br cells. Furthermore, DOX-PLGA@CM is equipped with naturally selected molecules for BBB penetration, as evidenced by its boosted capacity in entering …

Mediator Kinase Inhibitors For Breast Cancer Therapy, Xiaokai Ding

Theses and Dissertations

Breast cancers (BrCa) that overexpress oncogenic tyrosine kinase receptor HER2 are treated with HER2-targeting antibodies (such as trastuzumab) or small-molecule kinase inhibitors (such as lapatinib). However, most patients with metastatic HER2+ BrCa have intrinsic resistance and nearly all eventually become resistant to HER2-targeting therapy. Resistance to HER2-targeting drugs frequently involves transcriptional reprogramming associated with constitutive activation of different signaling pathways. We have investigated the role of CDK8/19 Mediator kinase, a regulator of transcriptional reprogramming, in the response of HER2+ BrCa to HER2-targeting drugs. Selective CDK8/19 inhibitors (senexin B and SNX631) showed synergistic interactions with lapatinib and trastuzumab in a panel …

Spatial Metrics Of Interaction Between Cd163-Positive Macrophages And Cancer Cells And Progression-Free Survival In Chemo-Treated Breast Cancer, Brenton Maisel, Misung Yi, Amy R Peck, Yunguang Sun, Jeffrey A Hooke, Albert J Kovatich, Craig D Shriver, Hai Hu, Marja T Nevalainen, Takemi Tanaka, Nicole L Simone, Li Lily Wang, Hallgeir Rui, I Chervoneva

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor-associated macrophages (TAMs) promote progression of breast cancer and other solid malignancies via immunosuppressive, pro-angiogenic and pro-metastatic effects. Tumor-promoting TAMs tend to express M2-like macrophage markers, including CD163. Histopathological assessments suggest that the density of CD163-positive TAMs within the tumor microenvironment is associated with reduced efficacy of chemotherapy and unfavorable prognosis. However, previous analyses have required research-oriented pathologists to visually enumerate CD163+ TAMs, which is both laborious and subjective and hampers clinical implementation. Objective, operator-independent image analysis methods to quantify TAM-associated information are needed. In addition, since M2-like TAMs exert local effects on cancer cells through direct juxtacrine cell-to-cell interactions, …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports (ETD)

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

The Context-Dependent Impact Of Integrin-Associated Cd151 And Other Tetraspanins On Cancer Development And Progression: A Class Of Versatile Mediators Of Cellular Function And Signaling, Tumorigenesis And Metastasis, Sonia F. Erfani, Hui Hua, Yueyin Pan, Binhua P. Zhou, Xiuwei H. Yang

Molecular and Cellular Biochemistry Faculty Publications

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Heat Shock Protein 90 (Hsp90)-Inhibitor-Luminespib-Loaded-Protein-Based Nanoformulation For Cancer Therapy, Ankit K. Rochani, Sivakumar Balasubramanian, Aswathy Ravindran Girija, Toru Maekawa, Gagan Kaushal, Phd, D Sakthi Kumar

College of Pharmacy Faculty Papers

Drugs targeting heat shock protein 90 (Hsp90) have been extensively explored for their anticancer potential in advanced clinical trials. Nanoformulations have been an important drug delivery platform for the anticancer molecules like Hsp90 inhibitors. It has been reported that bovine serum albumin (BSA) nanoparticles (NPs) serve as carriers for anticancer drugs, which have been extensively explored for their therapeutic efficacy against cancers. Luminespib (also known as NVP-AUY922) is a new generation Hsp90 inhibitor that was introduced recently. It is one of the most studied Hsp90 inhibitors for a variety of cancers in Phase I and II clinical trials and is …

Flavonoids And Other Polyphenols Act As Epigenetic Modifiers In Breast Cancer., Priyanga Selvakumar, Aja Badgeley, Paige Murphy, Hina Anwar, Urvashi Sharma, Katharine Lawrence, Ashakumary Lakshmikuttyamma

College of Pharmacy Faculty Papers

Breast cancer is a common cancer that occurs due to different epigenetic alterations and genetic mutations. Various epidemiological studies have demonstrated an inverse correlation between breast cancer incidence and flavonoid intake. The anti-cancer action of flavonoids, a class of polyphenolic compounds that are present in plants, as secondary metabolites has been a major topic of research for many years. Our review analysis demonstrates that flavonoids exhibit anti-cancer activity against breast cancer occurring in different ethnic populations. Breast cancer subtype and menopausal status are the key factors in inducing the flavonoid's anti-cancer action in breast cancer. The dose is another key …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Heterogeneity And Plasticity Of Human Breast Cancer Cells In Response To Molecularly-Targeted Drugs, Emira Bousoik, Ramina Nabiee, Farideh Amirrad, Ashley Nichols, Rebecca Witt, Parvin Mahdipoor, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Non-responsive subpopulation of tumor cells, and acquired resistance in initially responsive cells are major challenges for cancer therapy with molecularly-targeted drugs. While point mutations are considered the major contributing factor to acquired resistance, in this study we explored the role of heterogeneity and plasticity of selected human breast cancer cell lines (MDA-MB-231, MDA-MB-468, and AU565) in their initial and adjusted response, respectively, to ruxolitinib, everolimus, and erlotinib. After determination of lethal concentration for 50% cell death (LC50), cells were exposed to selected drugs using three different approaches: single exposure to 4 × LC50 and collection of surviving cells, multiple exposures …

Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 …

Novel Flexible Heteroarotinoid, Sl-1-39, Inhibits Her2-Positive Breast Cancer Cell Proliferation By Promoting Lysosomal Degradation Of Her2., Hongye Zou, Mary B. Sevigny, Shengquan Liu, David T. Madden, Maggie C. Louie

Faculty Publications & Research of the TUC College of Pharmacy

SL-1-39 [1-(4-chloro-3-methylphenyl)-3-(4-nitrophenyl)thiourea] is a new flexible heteroarotinoid (Flex-Het) analog derived from the parental compound, SHetA2, previously shown to inhibit cell growth across multiple cancer types. The current study aims to determine growth inhibitory effects of SL-1-39 across the different subtypes of breast cancer cells and delineate its molecular mechanism. Our results demonstrate that while SL-1-39 blocks cell proliferation of all breast cancer subtypes tested, it has the highest efficacy against HER2+ breast cancer cells. Molecular analyses suggest that SL-1-39 prevents S phase progression of HER2+ breast cancer cells (SKBR3 and MDA-MB-453), which is consistent with reduced expression of key cell-cycle …

Drug Utilization Review Of Anticancer Drugs With Otherdrugs In Breast Cancer Patients, Mahadev Rao Dr

Manipal College of Pharmaceutical Sciences, Manipal Theses and Dissertations

Background: To study the prescribing pattern of chemotherapeutic drugs in Breast Cancer patients and to survey the prevalence of exigent drug-drug interactions (DDIs) between chemotherapeutic drugs and non-chemotherapeutic drugs and evaluate the risk factors associated with these drug-drug interactions in India. Methods: All discharged patients’ data in the Department of Oncology were collected from September 2019 to March 2020 with the help of Hospital Information System and inpatient file of the breast cancer patients collected from the Medical Records Department. Drugs were screened for interactions by Micromedex solutions database and Epocrates database. Descriptive statistics were generated and was used to …