Medical Pharmacology Commons^™

Dose-Dependent Pharmacodynamic Interaction Between Fasudil, A Rho Kinase Inhibitor, And Doxorubicin In The Mcf-7 Breast Cancer Cell Line, Ahmed B. Abdulwahid, Shaymaa F. Abbas, Dhuha E. Omran, Nehaya M. Al-Aubody, Sara A. Yaseen

Maaen Journal for Medical Sciences

Background: It is necessary to seek combination therapy that uses non-traditional cytotoxic drugs to mitigate the side effects of doxorubicin. Recently, Rho-associated protein kinase (ROCK) inhibitors have exhibited promising antitumor activity in both experimental and clinical studies

Aim: This study aimed to characterize the pharmacodynamic interaction between fasudil, a ROCK inhibitor, and doxorubicin in MCF-7 breast cancer cells by evaluating their cytotoxic effects and quantifying drug interactions using the Chou–Talalay principle.

Methods: Doxorubicin, fasudil, and their combined fractions were evaluated to investigate their cytotoxic impact on the MCF-7 cell line using the MTT  method. The cells were treated with …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

Silmitasertib (Cx-4945) Disrupts Erî±/Hsp90 Interaction And Drives Proteolysis Through The Disruption Of Ck2β Function In Breast Cancer Cells, Hogyoung Kim, Emma Elkins, Rahib Islam, Bo Cao, Nour Abbes, Kaela Battles, Sihyoung Kim, Sichan Kim, Christopher Williams

School of Graduate Studies Faculty Publications

Aberrant estrogen receptor (ERα) signaling mediates detrimental effects of tamoxifen including drug resistance and endometrial hyperplasia. ERα36, an alternative isoform of ERα, contributes to these effects. We have demonstrated that CK2 modulates ERα expression and function in breast cancer (BCa). Here, we assess if CX-4945 (CX), a clinical stage CK2 inhibitor, can disrupt ERα66 and ERα36 signaling in BCa. Using live cell imaging, we assessed the antiproliferative effects of CX in tamoxifen-sensitive and tamoxifen-resistant BCa cells in monolayer and/or spheroid cultures. CX-induced alterations in ERα66 and ERα36 mRNA and protein expression were assessed by RT-PCR and immunoblot. Co-immunoprecipitation was performed …

A Telehealth-Delivered Tai Chi Intervention (Taichi4joint) For Managing Aromatase Inhibitor-Induced Arthralgia In Patients With Breast Cancer During Covid-19: Longitudinal Pilot Study, Sameh Gomaa, Carly West, Ana Maria Lopez, Tingting Zhan, Max Schnoll, Maysa Abu-Khalaf, Andrew B. Newberg, Kuang-Yi Wen

Department of Medical Oncology Faculty Papers

Background: Estrogen receptor-positive breast cancer is the most common type of breast cancer in postmenopausal women. Aromatase inhibitors (AIs) are the endocrine therapy of choice recommended for these patients. Up to 50% of those treated with an AI develop arthralgia, often resulting in poor adherence and decreased quality of life.

Objective: The study is a single-arm longitudinal pilot study aiming to evaluate the safety, feasibility, acceptability, and potential efficacy of TaiChi4Joint, a remotely delivered 12-week tai chi intervention designed to relieve AI-induced joint pain.

Methods: Women diagnosed with stage 0-III breast cancer who received an AI for at least 2 …

Ethanol Exposure Up-Regulates Pd-L1/Pd-1 Immune Checkpoint Pathway And Promotes Mammary Tumor Development, Wenhua Xu, Linqing Wu, Mei Xu, Jia Luo, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Alcohol consumption in women enhances breast cancer incidence and ethanol is the main causal factor. Compromised host immunity through immunosuppression facilitates the development of many types of cancer, including breast cancer. Immune cells in breast tissues, particularly tumor-infiltrating CD8 cytotoxic T cells, play a critical role in the host anti-tumor immunity against breast tumorigenesis. These cytotoxic T cells are the major immune cells to carry out anti-tumor immunity through their cytotoxic effector function, which can be regulated by immune checkpoint pathways. The PD-1/PD-L1 pathway (the interaction between programmed death-1, PD-1, and its ligand, programmed deathligand 1, PD-L1) is the best …

Isobavachalcone Sensitizes Cells To E2-Induced Paclitaxel Resistance By Down-Regulating Cd44 Expression In Er+ Breast Cancer Cells, Junfeng Shi, Yi Chen, Wenxing Chen, Cuiju Tang, Honghong Zhang, Yuetong Chen, Xiuwei H. Yang, Zhi Xu, Jingsun Wei, Jinfei Chen

Pharmacology and Nutritional Sciences Faculty Publications

Oestrogen receptor (ER) is expressed in approximately 60%‐70% of human breast cancer. Clinical trials and retrospective analyses have shown that ER‐positive (ER+) tumours are more tolerant to chemotherapeutic drug resistance than ER‐negative (ER−) tumours. In addition, isobavachalcone (IBC) is known as a kind of phytoestrogen with antitumour effect. However, the underlying mechanism of IBC in ER+ breast cancer needs to be elucidated further. Our in vitro experiments showed that IBC could attenuate 17β‐estradiol (E₂)‐induced paclitaxel resistance and that E₂ could stimulate CD44 expression in ER+ breast cancer cells but not in ER− cells. Meanwhile, E₂ could …

Ag-205 For The Treatment Of Breast Cancer, Rolf Joseph Craven

Pharmacology and Nutritional Sciences Faculty Patents

Compositions, methods, and combination therapies for the treatment of cancers, including lymphomas, leukemias, melanomas, lung cancer, and metastatic disease, are provided. Specifically, compositions comprising ligands to Pgrmc1 are disclosed for use in treating and inhibiting tumor growth and progression and inhibition of metastases. The compositions and methods using these ligands can be used alone or in combination with other reagents and cancer treatment modalities.

Pathologic Evaluation Of Tumor-Associated Macrophage Density And Vessel Inflammation In Invasive Breast Carcinomas, Yoshihiro Morita, Roy Zhang, Macall Leslie, Smita Adhikari, Nafis Hasan, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumor-associated macrophages (TAMs) are major constituents of the tumor microenvironment in solid tumors and have been implicated as mediators of tumor progression, invasion and metastasis. Correspondingly, accumulation of TAMs is associated with unfavorable clinical outcomes in numerous types of solid tumors. E-selectin is a hallmark of inflammation and a key adhesion molecule that accommodates the initial contact of circulating immune cells with the inflamed vessel surface. Currently, the association between E-selectin and TAMs is not fully elucidated; therefore, the present study investigated the association between vessel inflammation, TAM infiltration, and clinical outcome in breast cancer. A total of 53 procedure-naïve …

Dub3 Inhibition Suppresses Breast Cancer Invasion And Metastasis By Promoting Snail1 Degradation, Yadi Wu, Yu Wang, Yiwei Lin, Yajuan Liu, Yifan Wang, Jianhang Jia, Puja Singh, Young-In Chi, Chi Wang, Chenfang Dong, Wei Li, Min Tao, Dana L. Napier, Qiuying Shi, Jiong Deng, B. Mark Evers, Binhua P. Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Snail1, a key transcription factor of epithelial–mesenchymal transition (EMT), is subjected to ubiquitination and degradation, but the mechanism by which Snail1 is stabilized in tumours remains unclear. We identify Dub3 as a bona fide Snail1 deubiquitinase, which interacts with and stabilizes Snail1. Dub3 is overexpressed in breast cancer; knockdown of Dub3 resulted in Snail1 destabilization, suppressed EMT and decreased tumour cell migration, invasion, and metastasis. These effects are rescued by ectopic Snail1 expression. IL-6 also stabilizes Snail1 by inducing Dub3 expression, the specific inhibitor WP1130 binds to Dub3 and inhibits the Dub3-mediating Snail1 stabilization in vitroand in vivo. …

Combined Antiproliferative Effects Of The Aminoalkylindole Win55,212-2 And Radiation In Breast Cancer Cells, Sean Emery

Theses and Dissertations

The potential antitumor activity of mixed CB1/CB2 cannabinoid receptor agonists, such as the aminoalkylindole WIN55,212-2 (WIN2), has been extensively studied, but little information is available as to their potential interaction with conventional cancer therapies, such as ionizing radiation (IR). In the present work, we investigated the effects of WIN2 on the antiproliferative effects of radiation in human (MCF-7 and MDA-MB-231) and murine (4T1) breast cancer cells, as well as an immortalized human breast epithelial cell line (MCF-10A). WIN2 or radiation alone inhibited breast tumor growth, while the combination of WIN2 and radiation was more effective than either agent alone in …

Is Less Really More?: Determining The Efficacy And Advantages Of Low Dose Chemotherapy, Natalie Toews

Senior Honors Theses

Chemotherapy is the preferred treatment for patients with breast cancer nationwide; however, the dosage and duration of this treatment have come under recent scrutiny. The efficacy of high dose chemotherapy is many times inadequate, and the adverse physical effects resulting from this regimen have a negative holistic impact on the patients. Studies suggest that low dose chemotherapy, through antiangiogenesis, affects the spread of breast cancer carcinomas and may produce less harmful side effects in relation to the heart, brain, and eyes. Thus, oncological research proposes that a low dose regimen improves the patient’s quality of life and may be an …

C-Abl And Arg Drive Cancer Chemoresistance Via Activation Of Multiple Signaling Pathways, Jonathan Thomas Sims

Theses and Dissertations--Pharmacology and Nutritional Sciences

Despite 35 years of clinical trials, there has been little improvement in one-year survival rates with any chemotherapeutic regimen for the treatment of metastatic melanoma due to resistance to all known agents. Regardless of advances in detection and prevention, diagnosis of metastatic disease remains a death sentence. Resistance mechanisms, including aberrant kinase signaling and drug transport pumps, indicate a need for identification of other therapeutic targets that impinge upon multiple signaling pathways. The Abl family of non-receptor tyrosine kinases (c-Abl, Arg) has been indicted as a causative force in leukemia for more than three decades; however, their role in solid …

Chronic Diseases: The Emerging Pandemic., Andre Terzic, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

According to the 2011 World Health Organization Global Status Report, of the 57 million annual global deaths – a staggering 36 million or over 63% are due to chronic diseases.¹ Four noncommunicable diseases - namely cardiovascular, cancer, diabetes, and chronic respiratory diseases - emerge as the leading cause of mortality in the world, accounting respectively for 17, 7.6, 4.2, and 1.3 million deaths based on the latest available global epidemiology data. By 2020, global deaths due to chronic diseases are projected to worsen by at least 15 to 20%. It is estimated that the four major noncommunicable diseases will …

The Substituted Pyrrole Jb-03-14 Induces Autophagic Cell Death And Growth Arrest In Breast Tumor Cells, Christopher Ryan Arthur

Theses and Dissertations

The use of chemotherapy in the treatment of cancer has stimulated the demand for better chemotherapeutic agents that are more potent at destroying tumor cell populations and more selective for the specific tumor versus normal host tissues. This project is directed at discovering new anti-tumor agents that are effective against breast cancer based on structures derived from marine organisms, specifically brominated pyrroles. We utilized an in vitro breast cancer model to study the effects of pyrroles on tumor proliferation and survival, as well as growth arrest and cell death. Our findings indicate that the substituted pyrrole JG-03-14 induces time dependent …

Influence Of The Vitamin D3 Analog Eb 1089 On Senescence And Cell Death Pathways In The Response Of Breast Tumor Cells To Ionizing Radiation, Gerald Alan Demasters

Theses and Dissertations

A senescence-like growth arrest succeeded by rapid recovery of proliferative capacity is observed in MCF-7 breast tumor cells exposed to fractionated radiation (5 x 2Gy) alone. Exposure to the vitamin D3 analog EB 1089 (100nM) prior to irradiation converts the initial growth arrest response to cell death in part through the inhibition of radiation-induced senescence and promotion of both apoptotic and autophagic cell death. More importantly, EB 1089 was shown to profoundly reduce the rate of recovery following fractionated irradiation. The effect of EB 1089 on the temporal response to radiation is also observed in MCF-7 cells expressing caspase 3, …