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Small-Molecule Ferroptotic Agents with Potential to Selectively Target Cancer Stem Cells
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Abstract<p>Effective management of advanced cancer requires systemic treatment including small molecules that target unique features of aggressive tumor cells. At the same time, tumors are heterogeneous and current evidence suggests that a subpopulation of tumor cells, called tumor initiating or cancer stem cells, are responsible for metastatic dissemination, tumor relapse and possibly drug resistance. Classical apoptotic drugs are less effective against this critical subpopulation. In the course of generating a library of open-chain epothilones, we discovered a new class of small molecule anticancer agents that has no effect on tubulin but instead kills selected cancer cell lines by harnessing reactive oxygen species to induce ferroptosis. Interestingly, we find that drug sensitivity is highest in tumor cells with a mesenchymal phenotype. Furthermore, these compounds showed enhanced toxicity towards mesenchymal breast cancer populations with cancer stem cell properties <italic>in vitro</italic>. In summary, we have identified a new class of small molecule ferroptotic agents that warrant further investigation.</p>
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Publication Date
Tue Jul 04 2023
Journal Name
Ankara Universitesi Eczacilik Fakultesi Dergisi
ANTIANGIOGENIC ACTIVITY AND ROS-MEDIATED LUNG CANCER CELL LINE INJURY OF ZERUMBONE
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Objective: Zerumbone (ZER) is a well-known natural compound that has been reported to have anti-cancer effect. Thus, this study investigated the ZER potential to inhibit Thymidine Phosphorylase (TP) and the ability to trigger Reactive oxygen species (ROS)-mediated cytotoxicity in non-small cell lung cancer, NCI-H460, cell line. Material and Method: The antiangiogenic activity for ZER was evaluated by using the thymidine phosphorylase inhibitory test. Reactive oxygen species (ROS) production was determined via DCFDA dye by using flow cytometry. Result and Discussion: ZER was found to be potent TP inhibitory with the IC50 value of 50.3± 0.31 μg/ml or 230±1.42 µM. NCI-H460 cells upon treatment with ZER produced sign

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Publication Date
Thu Jul 20 2023
Journal Name
Journal Of Advanced Biotechnology And Experimental Therapeutics
No evidence of relationship between colorectal cancer susceptibility and ERCC2 gene polymorphisms
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Background: Excision repair cross-complementing group 2 gene (ERCC2) polymorphisms have been linked as being a risk factor for colorectal cancer (CRC) emergence. However, data from several studies are contradictory. To validate genetic biomarkers of the CRC; the impact of the following ERCC2 polymorphism (rs1799793 and rs238406) was examined on CRC susceptibility among sample of Iraqi population. Methods: A total of 126 subjects were enrolled in this case control study; 78 CRC patients and 48 apparently healthy individuals who are age, gender, smoking status and BMI matched. Polymerase chain reaction (PCR) was used for genotyping, followed by sequencing then the association between genetic polymorphisms and CRC risk was investigate

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Publication Date
Fri Sep 01 2017
Journal Name
Gulf Journal Of Oncology
Clinical and Pathological Characteristics of Triple Positive Breast Cancer among Iraqi Patients
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Background: Breast cancer is the most common malignancy affecting the Iraqi population and the leading cause of cancer related mortality among Iraqi women. It has been well documented that prognosis of patients depends largely upon the hormone receptor contents and HER-2 over expression of their neoplasm. Recent studies suggest that Triple Positive (TP) tumors, bearing the three markers, tend to exhibit a relatively favorable clinical behavior in which overtreatment is not recommended. Aim: To document the different frequencies of ER/PR/HER2 breast cancer molecular subtypes focusing on the Triple Positive pattern; correlating those with the corresponding clinico-pathological characteristics among a sample of Iraqi patients diagnosed with th

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Publication Date
Thu Oct 06 2022
Journal Name
Advances In Systems Science And Applications
Stability and Bifurcation of a Delay Cancer Model in the Polluted Environment
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It is well known that the spread of cancer or tumor growth increases in polluted environments. In this paper, the dynamic behavior of the cancer model in the polluted environment is studied taking into consideration the delay in clearance of the environment from their contamination. The set of differential equations that simulates this epidemic model is formulated. The existence, uniqueness, and the bound of the solution are discussed. The local and global stability conditions of disease-free and endemic equilibrium points are investigated. The occurrence of the Hopf bifurcation around the endemic equilibrium point is proved. The stability and direction of the periodic dynamics are studied. Finally, the paper is ended with a numerical simul

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Publication Date
Thu Feb 16 2023
Journal Name
International Journal Of Breast Cancer
Galangin-Loaded Gold Nanoparticles: Molecular Mechanisms of Antiangiogenesis Properties in Breast Cancer
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Angiogenesis is important for tissue during normal physiological processes as well as in a number of diseases, including cancer. Drug resistance is one of the largest difficulties to antiangiogenesis therapy. Due to their lower cytotoxicity and stronger pharmacological advantage, phytochemical anticancer medications have a number of advantages over chemical chemotherapeutic drugs. In the current study, the effectiveness of AuNPs, AuNPs-GAL, and free galangin as an antiangiogenesis agent was evaluated. Different physicochemical and molecular approaches have been used including the characterization, cytotoxicity, scratch wound healing assay, and gene expression of VEGF and ERKI in MCF-7 and MDA-MB-231 human breast cancer cell line. Re

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Publication Date
Mon Mar 23 2020
Journal Name
International Journal Of Nanoscience
Gold Nanoparticles Synthesis Using Environmentally Friendly Approach for Inhibition Human Breast Cancer
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In this study, gold nanoparticles were synthesized in a single step biosynthetic method using aqueous leaves extract of thymus vulgaris L. It acts as a reducing and capping agent. The characterizations of nanoparticles were carried out using UV-Visible spectra, X-ray diffraction (XRD) and FTIR. The surface plasmon resonance of the as-prepared gold nanoparticles (GNPs) showed the surface plasmon resonance centered at 550[Formula: see text]nm. The XRD pattern showed that the strong four intense peaks indicated the crystalline nature and the face centered cubic structure of the gold nanoparticles. The average crystallite size of the AuNPs was 14.93[Formula: see text]nm. Field emission scanning electron microscope (FESEM) was used to s

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Publication Date
Thu Mar 07 2024
Journal Name
Oncology Letters
Effect of valproic acid on histone deacetylase expression in oral cancer (Review)
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Publication Date
Sun Jun 02 2013
Journal Name
Baghdad Science Journal
Comparison of The Effect of Aqueous Extracts of two Plants, Origanum Vulgare L. and Fenugreek Seeds with Anticancer Drug Cis-Platin on the Growth of Cancer Cell Lines
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This study involved the effect of the aqueous extracts of two plants, Origanum vulgare L.(1), Trigonella Foenum Graecum L. (Fenugreek) seeds(2) on the growth of cancer cell lines. Rhabdomyo sarcomas (RD) of human cell line and female intestine cells of Albino mice (L20B) in vitro System. These extracts were compared with the known anticancer drug Cis-platinum(Cis-Pt) as a positive control. The phytochemical tests were used for screening the active compounds in plants. The inhibition activity assay was used as a parameter of the cytotoxic effect of these extracts. Cancer cell lines were treated with four concentrations of Cis-platin, 31.25, 62.5, 125 and 250 ?g/ml for 72 hour exposure time. The same concentrations were used for the other ext

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Publication Date
Sat Feb 01 2020
Journal Name
Journal Of Economics And Administrative Sciences
The Relationship between the Strategies of E-marketing mix and Marketing Effectiveness of the Palestinian Small Business Industrial Organizations in the City of Hebron
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In the city of Hebron, small business industrial organizations face a major challenge related to its ability to reach, attract and sustain a sufficient number of customers in order to ensure its continuity and sustainability. The research problem is summarized in an attempt to reveal how the e-marketing could improve and support the marketing effectiveness of small business industrial organizations in the city of Hebron/Palestine. The importance of this research stems from the fact that it addresses a new knowledge branch of the field of marketing, which is electronic marketing for small business organizations, and the fact that the research highlights appropriate marketing solutions for these organizations in light of the Intern

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Publication Date
Tue Apr 18 2023
Journal Name
Corporate Reputation Review
The Absorptive Capacity of Knowledge as an Approach for Building Strategic Reliability in the Sponge Organizations/Small Organizations in Kirkuk Governorate as a Model
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