scholarly journals Bioprinted Cancer Model of Neuroblastoma in a Renal Microenvironment as an Efficiently Applicable Drug Testing Platform

2021 ◽  
Vol 23 (1) ◽  
pp. 122
Author(s):  
Dongwei Wu ◽  
Johanna Berg ◽  
Birte Arlt ◽  
Viola Röhrs ◽  
Munir A. Al-Zeer ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Human Cancer ◽  
Early Death ◽  
Human Kidney ◽  
Therapeutic Window ◽  
Cancer Model ◽  
Cell Type ◽  
Anaplastic Lymphoma ◽  
New Anticancer Drugs

Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.

scholarly journals New selective thiolate gold(i) complexes inhibit the proliferation of different human cancer cells and induce apoptosis in primary cultures of mouse colon tumors

2020 ◽  
Vol 49 (6) ◽  
pp. 1915-1927 ◽  
Author(s):  
Elisa Abas ◽  
Raquel Pena-Martinez ◽  
Diego Aguirre-Ramírez ◽  
Antonio Rodriguez-Dieguez ◽  
Mariano Laguna ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Human Cancer ◽  
Primary Cultures ◽  
Colon Tumors ◽  
Human Cancer Cells ◽  
Mouse Colon

New thiolate gold(i) complexes with P(NMe2)3 (HMPT) as phosphane group have been developed as proapoptotic and selective anticancer drugs.

scholarly journals Salinomycin Treatment Specifically Inhibits Cell Proliferation of Cancer Stem Cells Revealed by Longitudinal Single Cell Tracking in Combination with Fluorescence Microscopy

2020 ◽  
Vol 10 (14) ◽  
pp. 4732
Author(s):  
Sofia Kamlund ◽  
Birgit Janicke ◽  
Kersti Alm ◽  
Stina Oredsson
Keyword(s):  
Cell Proliferation ◽  
Fluorescence Microscopy ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Digital Holography ◽  
Cell Tracking ◽  
Population Based ◽  
Longitudinal Tracking ◽  
Long Time ◽  
New Anticancer Drugs

A cell line derived from a tumor is a heterogeneous mixture of phenotypically different cells. Such cancer cell lines are used extensively in the search for new anticancer drugs and for investigating their mechanisms of action. Most studies today are population-based, implying that small subpopulations of cells, reacting differently to the potential drug go undetected. This is a problem specifically related to the most aggressive single cancer cells in a tumor as they appear to be insensitive to the drugs used today. These cells are not detected in population-based studies when developing new anticancer drugs. Thus, to get a deeper understanding of how all individual cancer cells react to chemotherapeutic drugs, longitudinal tracking of individual cells is needed. Here we have used digital holography for long time imaging and longitudinal tracking of individual JIMT-1 breast cancer cells. To gain further knowledge about the tracked cells, we combined digital holography with fluorescence microscopy. We grouped the JIMT-1 cells into different subpopulations based on expression of CD24 and E-cadherin and analyzed cell proliferation and cell migration for 72 h. We investigated how the cancer stem cell (CSC) targeting drug salinomycin affected the different subpopulations. By uniquely combining digital holography with fluorescence microscopy we show that salinomycin specifically targeted the CD24− subpopulation, i.e., the CSCs, by inhibiting cell proliferation, which was evident already after 24 h of drug treatment. We further found that after salinomycin treatment, the surviving cells were more epithelial-like due to the selection of the CD24+ cells.

scholarly journals Overview of the Anticancer Potential of the “King of Spices” Piper nigrum and Its Main Constituent Piperine

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 747
Author(s):  
Eleonora Turrini ◽  
Piero Sestili ◽  
Carmela Fimognari
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Bioactive Molecules ◽  
Piper Nigrum ◽  
Comprehensive Overview ◽  
Anticancer Properties ◽  
Toxicological Profile ◽  
Key Pathways ◽  
New Anticancer Drugs

The main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient’s quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents—not limited to the well-known piperine—whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients.

scholarly journals Regulations of P-Glycoprotein/ABCB1/MDR1 in Human Cancer Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kazuhiro Katayama ◽  
Kohji Noguchi ◽  
Yoshikazu Sugimoto
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Kinase Inhibitors ◽  
Human Cancer ◽  
Drug Uptake ◽  
Drug Efflux ◽  
Toxic Substances ◽  
Human Cancer Cells ◽  
P Glycoprotein ◽  
Transporter Family

Multidrug resistance (MDR) in cancer cells is a phenotype whereby cells display reduced sensitivity to anticancer drugs, based on a variety of mechanisms, including an increase in drug efflux, the reduction of drug uptake, the activation of cell growth and survival signaling, the promotion of DNA repair, and the inhibition of apoptosis signaling. Increased expression of the plasma membrane drug efflux pumps, the ATP-binding cassette (ABC) transporters, is involved in MDR. P-Glycoprotein/ABCB1 is a member of the ABC transporter family, and facilitates the efflux of various anticancer drugs, including anthracyclines, vinca alkaloids, epipodophyllotoxins, taxanes, and kinase inhibitors, from cells. P-Glycoprotein is also expressed in normal tissues and cells, including the kidney, liver, colon, and adrenal gland, to transport and/or secrete substrates and at the blood-brain, blood-placenta, and blood-testis barriers to protect these tissues from toxic substances. To understand the mechanistic functions of P-glycoprotein and to overcome MDR, investigators have identified the substrates and competitive inhibitors of P-glycoprotein. Recently, we and other groups reported associations between cellular signaling pathways and the expression, stability, degradation, localization, and activity of P-glycoprotein. The present review summarizes the currently available information about the transcriptional and posttranslational regulation of P-glycoprotein expression and function.

SV40 T/t-common polypeptide enhances the sensitivity of HER2-overexpressing human cancer cells to anticancer drugs cisplatin and doxorubicin

2012 ◽  
Vol 324 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Shu-Ping Hsueh ◽  
Jia-Ling Du ◽  
Wen-Bin Hsu ◽  
Chung-An Fang ◽  
Hsuan Liu ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Human Cancer ◽  
Human Cancer Cells

Risk of Incremental Toxicities and Associated Costs of New Anticancer Drugs: A Meta-Analysis

2014 ◽  
Vol 32 (32) ◽  
pp. 3634-3642 ◽  
Author(s):  
Saroj Niraula ◽  
Eitan Amir ◽  
Francisco Vera-Badillo ◽  
Bostjan Seruga ◽  
Alberto Ocana ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Anticancer Drugs ◽  
Meta Analysis ◽  
Molecular Target ◽  
Chemotherapeutic Agents ◽  
Targeted Agents ◽  
Treatment Frequency ◽  
Experimental Drugs ◽  
Grade 3 ◽  
New Anticancer Drugs

Purpose There are increasing reports of rare but serious toxicities caused by new anticancer drugs, and there are costs associated with their management. Methods We identified anticancer drugs approved by the US Food and Drug Administration from 2000 to 2011 and pivotal trials supporting their registration. Twelve frequent grade 3 to 4 adverse event (AEs) were weighted and pooled in a meta-analysis. Estimates of incremental drug prices and incremental costs for management of AEs were calculated according to type of new agent based on target specificity. Results We identified 41 studies comprising 27,539 patients and evaluating 19 experimental drugs. Agents directed against a specific molecular target on cancer cells had a lower incidence of grade 3 to 4 toxicities compared with controls (median risk ratio [RR], 0.67; P = .22), whereas less-specific targeted agents, including angiogenesis inhibitors (median RR, 3.39; P < .001) and chemotherapeutic agents (median RR, 1.73; P < .001), were more toxic. Risk was increased regardless of whether the control arm contained active treatment (RR, 2.11; P < .001) or not (RR, 3.02; P < .001). Median incremental drug price for experimental agents was $6,000 per patient per month. Median cost of managing toxicity was low compared with drug costs but higher than controls for treatment with less-specific targeted agents and chemotherapies. Conclusion Newly approved anticancer drugs are associated with increased toxicity, except for agents with a specific molecular target on cancer cells. Management of toxicity leads to a small increase in overall cost of treatment. Frequency of toxicity and associated costs are likely higher in less-selected patients treated in general oncologic practice. Development of biomarker-driven agents should be encouraged.

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