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Full-Text Articles in Pharmaceutics and Drug Design

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 Oct 2019

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 to ...


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 Feb 2019

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

College of Pharmacy (TUC) Publications and Research

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 ...


Companion Diagnostics For Breast Cancer Chemotherapeutics, Monica Tawadros, Michael Morin, Peter Gaines, Abiche H. Dewilde May 2017

Companion Diagnostics For Breast Cancer Chemotherapeutics, Monica Tawadros, Michael Morin, Peter Gaines, Abiche H. Dewilde

UMass Center for Clinical and Translational Science Research Retreat

Chemotherapy plays a major role in breast cancer treatment. However, not every chemotherapeutics is appropriate for each cancer due to the person’s individual cancer characteristics and whether the patient has developed chemoresistance to a particular drug. In this research, the InVitro-Q is used to detect subtle differences in tumor cell proliferation post-treatment with four-breast cancer chemotherapeutics used: paclitaxel, docetaxel, nocodazole, and cytochalasin B. Our multi-well cell-based sensor that can monitor real-time biological changes in living cells, such as mass redistribution, and viscoelasticity. This system provides unique kinetic information regarding the phenotypic change in the cells post treatment. Each drug ...


Therapeutic Efficacy And Safety Of Paclitaxel/Lonidamine Loaded Egfr-Targeted Nanoparticles For The Treatment Of Multi-Drug Resistant Cancer, Lara S. Jabr-Milane, Zhenfeng Duan, Mansoor M. Amiji Oct 2011

Therapeutic Efficacy And Safety Of Paclitaxel/Lonidamine Loaded Egfr-Targeted Nanoparticles For The Treatment Of Multi-Drug Resistant Cancer, Lara S. Jabr-Milane, Zhenfeng Duan, Mansoor M. Amiji

Mansoor M. Amiji

The treatment of multi-drug resistant (MDR) cancer is a clinical challenge. Many MDR cells over-express epidermal growth factor receptor (EGFR). We exploit this expression through the development of EGFR-targeted, polymer blend nanocarriers for the treatment of MDR cancer using paclitaxel (a common chemotherapeutic agent) and lonidamine (an experimental drug; mitochondrial hexokinase 2 inhibitor). An orthotopic model of MDR human breast cancer was developed in nude mice and used to evaluate the safety and efficacy of nanoparticle treatment. The efficacy parameters included tumor volume measurements from day 0 through 28 days post-treatment, terminal tumor weight measurements, tumor density and morphology assessment ...


Development And Evaluation Of Paclitaxel-Loaded Liposomal Formulations For Targeted Drug Delivery To Breast Cancer, Vinayagam Kannan Dec 2010

Development And Evaluation Of Paclitaxel-Loaded Liposomal Formulations For Targeted Drug Delivery To Breast Cancer, Vinayagam Kannan

Theses and Dissertations (ETD)

The objective of this work was to develop and evaluate paclitaxel-loaded liposomal formulations for targeted drug delivery to breast cancer. The liposomal formulation was optimized to maximize drug loading and physical stability. Cholesterol and saturated lipid content showed a negative influence on paclitaxel loading. Short-term stability studies showed that optimum drug-lipid ratio is necessary for adequate physical stability. Biodistribution studies in mouse xenografts bearing MDA-MB-231 breast cancer using near infrared fluorescence imaging showed that the accumulation of tumor vasculature targeted long-circulating liposomes (LCL) in the tumor was significantly less than non-targeted LCL at 48 h. The accumulation of these liposomes ...