scholarly journals Human Plasma-Derived 3D Cultures Model Breast Cancer Treatment Responses and Predict Clinically Effective Drug Treatment Concentrations

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1722 ◽  
Author(s):  
Kristin Calar ◽  
Simona Plesselova ◽  
Somshuvra Bhattacharya ◽  
Megan Jorgensen ◽  
Pilar de la Puente
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Human Plasma ◽  
Cell Lines ◽  
Single Cells ◽  
3D Culture ◽  
3D Models ◽  
Preclinical Models ◽  
Culture Model ◽  
3D Culture Model

Lack of efficacy and a low overall success rate of phase I-II clinical trials are the most common failures when it comes to advancing cancer treatment. Current drug sensitivity screenings present several challenges including differences in cell growth rates, the inconsistent use of drug metrics, and the lack of translatability. Here, we present a patient-derived 3D culture model to overcome these limitations in breast cancer (BCa). The human plasma-derived 3D culture model (HuP3D) utilizes patient plasma as the matrix, where BCa cell lines and primary BCa biopsies were grown and screened for drug treatments. Several drug metrics were evaluated from relative cell count and growth rate curves. Correlations between HuP3D metrics, established preclinical models, and clinical effective concentrations in patients were determined. HuP3D efficiently supported the growth and expansion of BCa cell lines and primary breast cancer tumors as both organoids and single cells. Significant and strong correlations between clinical effective concentrations in patients were found for eight out of ten metrics for HuP3D, while a very poor positive correlation and a moderate correlation was found for 2D models and other 3D models, respectively. HuP3D is a feasible and efficacious platform for supporting the growth and expansion of BCa, allowing high-throughput drug screening and predicting clinically effective therapies better than current preclinical models.

scholarly journals Oncogenic activation of FAK drives apoptosis suppression in a 3D-culture model of breast cancer initiation

Oncotarget ◽  
2016 ◽  
Vol 7 (43) ◽  
pp. 70336-70352 ◽  
Author(s):  
Scott Walker ◽  
Fiona Foster ◽  
Amber Wood ◽  
Thomas Owens ◽  
Keith Brennan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
3D Culture ◽  
Culture Model ◽  
Cancer Initiation ◽  
3D Culture Model

scholarly journals Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model

2018 ◽  
Author(s):  
Yung-Hsing Huang ◽  
Ommoleila Molavi ◽  
Abdulraheem Alshareef ◽  
Moinul Haque ◽  
Qian Wang ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Single Cells ◽  
Active Form ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Models ◽  
Oligonucleotide Array ◽  
Conventional Culture ◽  
3D Culture Model ◽  
Cells Cultured

Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid cancers, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (pSTAT3), being absent in MM cells cultured conventionally, became detectable after 1-2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in the 3D culture can generate results that are more representative of the disease.

scholarly journals Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model

2018 ◽  
Author(s):  
Yung-Hsing Huang ◽  
Ommoleila Molavi ◽  
Abdulraheem Alshareef ◽  
Moinul Haque ◽  
Qian Wang ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Single Cells ◽  
Active Form ◽  
Three Dimensional ◽  
3D Culture ◽  
3D Models ◽  
Oligonucleotide Array ◽  
Conventional Culture ◽  
3D Culture Model ◽  
Cells Cultured

Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid tumor types, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (phospho-STAT3 or pSTAT3), which was absent in MM cells cultured conventionally, became detectable after 1-2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in 3D culture can generate results that are more representative of the disease.

HER2-Associated Breast Cancer Signature Using a 3D Culture Model.

2009 ◽  
Author(s):  
P. Chaluvally-Raghavan ◽  
A. Zeisel ◽  
W. Koestler ◽  
J. Jacob-Hirsch ◽  
G. Rechavi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
3D Culture ◽  
Culture Model ◽  
3D Culture Model

Abstract 278: Deciphering circular RNA axes in early-onset breast cancer using a breast epithelial risk-progression 3D culture model

2020 ◽  
Author(s):  
Nataly Naser Al Deen ◽  
Nadia Atallah Lanman ◽  
Shirisha Chittiboyina ◽  
Sophie Lelièvre ◽  
Heinrich Zu Dohna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Onset ◽  
3D Culture ◽  
Circular Rna ◽  
Early Onset Breast Cancer ◽  
Culture Model ◽  
Breast Epithelial ◽  
3D Culture Model

scholarly journals Studying biomineralization pathways in a 3D culture model of breast cancer microcalcifications

Biomaterials ◽  
2018 ◽  
Vol 179 ◽  
pp. 71-82 ◽  
Author(s):  
Netta Vidavsky ◽  
Jennie AMR. Kunitake ◽  
Aaron E. Chiou ◽  
Paul A. Northrup ◽  
Teresa J. Porri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
3D Culture ◽  
Culture Model ◽  
3D Culture Model

scholarly journals Prognostic Breast Cancer Signature Identified from 3D Culture Model Accurately Predicts Clinical Outcome across Independent Datasets

PLoS ONE ◽  
2008 ◽  
Vol 3 (8) ◽  
pp. e2994 ◽  
Author(s):  
Katherine J. Martin ◽  
Denis R. Patrick ◽  
Mina J. Bissell ◽  
Marcia V. Fournier
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
3D Culture ◽  
Culture Model ◽  
3D Culture Model

scholarly journals Fucoxanthin Holds Potential to Become a Drug Adjuvant in Breast Cancer Treatment: Evidence from 2D and 3D Cell Cultures

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4288
Author(s):  
Fernanda Malhão ◽  
Ana Catarina Macedo ◽  
Carla Costa ◽  
Eduardo Rocha ◽  
Alice Abreu Ramos
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
3D Models ◽  
Anticancer Activities ◽  
Cytotoxic Effects ◽  
3D Cultures ◽  
3D Cell Cultures ◽  
Tumoral Cell ◽  
Microscopy Techniques ◽  
2D And 3D

Fucoxanthin (Fx) is a carotenoid derived from marine organisms that exhibits anticancer activities. However, its role as a potential drug adjuvant in breast cancer (BC) treatment is still poorly explored. Firstly, this study investigated the cytotoxic effects of Fx alone and combined with doxorubicin (Dox) and cisplatin (Cis) on a panel of 2D-cultured BC cell lines (MCF7, SKBR3 and MDA-MB-231) and one non-tumoral cell line (MCF12A). Fucoxanthin induced cytotoxicity against all the cell lines and potentiated Dox cytotoxic effects towards the SKBR3 and MDA-MB-231 cells. The combination triggering the highest cytotoxicity (Fx 10 µM + Dox 1 µM in MDA-MB-231) additionally showed significant induction of cell death and genotoxic effects, relative to control. In sequence, the same combination was tested on 3D cultures using a multi-endpoint approach involving bioactivity assays and microscopy techniques. Similar to 2D cultures, the combination of Fx and Dox showed higher cytotoxic effects on 3D cultures compared to the isolated compounds. Furthermore, this combination increased the number of apoptotic cells, decreased cell proliferation, and caused structural and ultrastructural damages on the 3D models. Overall, our findings suggest Fx has potential to become an adjuvant for Dox chemotherapy regimens in BC treatment.

scholarly journals Delivery of melittin-loaded niosomes for breast cancer treatment: an in vitro and in vivo evaluation of anti-cancer effect

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Farnaz Dabbagh Moghaddam ◽  
Iman Akbarzadeh ◽  
Ehsan Marzbankia ◽  
Mahsa Farid ◽  
Leila khaledi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Cell Lines ◽  
Encapsulation Efficiency ◽  
Inbred Mice ◽  
Breast Cancer Treatment ◽  
Anticancer Effect ◽  
Anti Cancer

Abstract Background Melittin, a peptide component of honey bee venom, is an appealing candidate for cancer therapy. In the current study, melittin, melittin-loaded niosome, and empty niosome had been optimized and the anticancer effect assessed in vitro on 4T1 and SKBR3 breast cell lines and in vivo on BALB/C inbred mice. "Thin-layer hydration method" was used for preparing the niosomes; different niosomal formulations of melittin were prepared and characterized in terms of morphology, size, polydispersity index, encapsulation efficiency, release kinetics, and stability. A niosome was formulated and loaded with melittin as a promising drug carrier system for chemotherapy of the breast cancer cells. Hemolysis, apoptosis, cell cytotoxicity, invasion and migration of selected concentrations of melittin, and melittin-loaded niosome were evaluated on 4T1 and SKBR3 cells using hemolytic activity assay, flow cytometry, MTT assay, soft agar colony assay, and wound healing assay. Real-time PCR was used to determine the gene expression. 40 BALB/c inbred mice were used; then, the histopathology, P53 immunohistochemical assay and estimate of renal and liver enzyme activity for all groups had been done. Results This study showed melittin-loaded niosome is an excellent substitute in breast cancer treatment due to enhanced targeting, encapsulation efficiency, PDI, and release rate and shows a high anticancer effect on cell lines. The melittin-loaded niosome affects the genes expression by studied cells were higher than other samples; down-regulates the expression of Bcl2, MMP2, and MMP9 genes while they up-regulate the expression of Bax, Caspase3 and Caspase9 genes. They have also enhanced the apoptosis rate and inhibited cell migration, invasion in both cell lines compared to the melittin samples. Results of histopathology showed reduce mitosis index, invasion and pleomorphism in melittin-loaded niosome. Renal and hepatic biomarker activity did not significantly differ in melittin-loaded niosome and melittin compared to healthy control. In immunohistochemistry, P53 expression did not show a significant change in all groups. Conclusions Our study successfully declares that melittin-loaded niosome had more anti-cancer effects than free melittin. This project has demonstrated that niosomes are suitable vesicle carriers for melittin, compare to the free form.

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