scholarly journals Tumor microenvironment in focus: LA-ICP-MS bioimaging of a preclinical tumor model upon treatment with platinum(iv)-based anticancer agents

Metallomics ◽  
2015 ◽  
Vol 7 (8) ◽  
pp. 1256-1264 ◽  
Author(s):  
Sarah Theiner ◽  
Christoph Kornauth ◽  
Hristo P. Varbanov ◽  
Markus Galanski ◽  
Sushilla Van Schoonhoven ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Anticancer Agents ◽  
Tumor Tissue ◽  
Tumor Model ◽  
High Concentration ◽  
Concentration Gradients ◽  
Icp Ms

Bioimaging of Pt in tumor tissue exhibited unexpected high concentration gradients, correlating with histologic features.

Can carboplatin replace cisplatin for intraperitoneal use?

2008 ◽  
Vol 18 (Suppl 1) ◽  
pp. 29-32 ◽  
Author(s):  
K. Fujiwara
Keyword(s):  
Anticancer Agents ◽  
Large Scale ◽  
Randomized Trials ◽  
Tumor Tissue ◽  
Review Article ◽  
High Concentration ◽  
Peritoneal Surface ◽  
Platinum Agent ◽  
The Us ◽  
Future Potential

lntraperitoneal (IP) chemotherapy is theoretically a feasible route for treating ovarian cancer. It is possible to expose tumor tissue disseminated peritoneal surface to extremely high concentration of anticancer agents. Three large-scale, randomized trials conducted in the US have demonstrated a significant improvement of progression survival and/or overall survival in IP chemotherapy arm over intravenous arm. Despite these favorable results, IP chemotherapy has not been accepted as standard care. One of the reasons for this is the use of cisplatin, which has been replaced by the less toxic platinum agent, carboplatin, when administered intravenously. In this review article, we discuss why IP chemotherapy using carboplatin has been ignored and its future potential

scholarly journals Recent Advances in Tumor Microenvironment Hydrogen Peroxide-Responsive Materials for Cancer Photodynamic Therapy

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Nan Yang ◽  
Wanyue Xiao ◽  
Xuejiao Song ◽  
Wenjun Wang ◽  
Xiaochen Dong
Keyword(s):  
Hydrogen Peroxide ◽  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Anticancer Agents ◽  
Inorganic Materials ◽  
High Concentration ◽  
Responsive Materials ◽  
Challenges And Opportunities

AbstractPhotodynamic therapy (PDT), as one of the noninvasive clinical cancer phototherapies, suffers from the key drawback associated with hypoxia at the tumor microenvironment (TME), which plays an important role in protecting tumor cells from damage caused by common treatments. High concentration of hydrogen peroxide (H2O2), one of the hallmarks of TME, has been recognized as a double-edged sword, posing both challenges, and opportunities for cancer therapy. The promising perspectives, strategies, and approaches for enhanced tumor therapies, including PDT, have been developed based on the fast advances in H2O2-enabled theranostic nanomedicine. In this review, we outline the latest advances in H2O2-responsive materials, including organic and inorganic materials for enhanced PDT. Finally, the challenges and opportunities for further research on H2O2-responsive anticancer agents are envisioned.

scholarly journals Differentiated glioblastoma cells accelerate tumor progression by shaping the tumor microenvironment via CCN1-mediated macrophage infiltration

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Atsuhito Uneda ◽  
Kazuhiko Kurozumi ◽  
Atsushi Fujimura ◽  
Kentaro Fujii ◽  
Joji Ishida ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Tumor Progression ◽  
Tumor Cells ◽  
In Silico ◽  
Tumor Tissue ◽  
The Cancer Genome Atlas ◽  
Macrophage Infiltration ◽  
Macrophage Migration

AbstractGlioblastoma (GBM) is the most lethal primary brain tumor characterized by significant cellular heterogeneity, namely tumor cells, including GBM stem-like cells (GSCs) and differentiated GBM cells (DGCs), and non-tumor cells such as endothelial cells, vascular pericytes, macrophages, and other types of immune cells. GSCs are essential to drive tumor progression, whereas the biological roles of DGCs are largely unknown. In this study, we focused on the roles of DGCs in the tumor microenvironment. To this end, we extracted DGC-specific signature genes from transcriptomic profiles of matched pairs of in vitro GSC and DGC models. By evaluating the DGC signature using single cell data, we confirmed the presence of cell subpopulations emulated by in vitro culture models within a primary tumor. The DGC signature was correlated with the mesenchymal subtype and a poor prognosis in large GBM cohorts such as The Cancer Genome Atlas and Ivy Glioblastoma Atlas Project. In silico signaling pathway analysis suggested a role of DGCs in macrophage infiltration. Consistent with in silico findings, in vitro DGC models promoted macrophage migration. In vivo, coimplantation of DGCs and GSCs reduced the survival of tumor xenograft-bearing mice and increased macrophage infiltration into tumor tissue compared with transplantation of GSCs alone. DGCs exhibited a significant increase in YAP/TAZ/TEAD activity compared with GSCs. CCN1, a transcriptional target of YAP/TAZ, was selected from the DGC signature as a candidate secreted protein involved in macrophage recruitment. In fact, CCN1 was secreted abundantly from DGCs, but not GSCs. DGCs promoted macrophage migration in vitro and macrophage infiltration into tumor tissue in vivo through secretion of CCN1. Collectively, these results demonstrate that DGCs contribute to GSC-dependent tumor progression by shaping a mesenchymal microenvironment via CCN1-mediated macrophage infiltration. This study provides new insight into the complex GBM microenvironment consisting of heterogeneous cells.

Dysprosium-enhanced MR imaging for tumor tissue characterization

1997 ◽  
Vol 38 (2) ◽  
pp. 281-286 ◽  
Author(s):  
C. Wang ◽  
A. Sundin ◽  
A. Ericsson ◽  
T. Bach-Gansmo ◽  
A. Hemmingsson ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Tissue Characterization ◽  
Tumor Tissue ◽  
Tumor Model ◽  
Human Colon ◽  
Mr Images ◽  
Histological Sections ◽  
Necrotic Tumor ◽  
Before And After ◽  
Weighted Sequences

Purpose: to evaluate dysprosium-enhanced MR imaging for differentiation between morphologically intact and necrotic tumor tissue in a tumor model. Material and Methods: A human colon carcinoma was transplanted subcutaneously into 9 nude (immunodeprived) rats. MR imaging was performed before and after injection of the dysprosium agent Dy-DTPA-BMA. T1-, T2- and T2*-weighted sequences were acquired. the tumors were dissected, histological sections were prepared, and compared with corresponding MR images. Results: in intact tissue, the MR signal intensity in the T2- and T2*-weighted images decreased after Dy injection and the delineation of the intact regions were sharp and corresponded well to the gross histological sections. Conclusion: Dy-enhanced MR imaging facilitated the differentiation between intact and necrotic tumor tissue.

scholarly journals Numerical Investigation of Drug Transport from Blood Vessels to Tumor Tissue Using a Tumor-Vasculature-on-a-Chip

2019 ◽  
Author(s):  
Wei Li ◽  
Hao-Fei Wang ◽  
Zhi-Yong Li ◽  
Tong Wang ◽  
Chun-Xia Zhao
Keyword(s):  
Tumor Microenvironment ◽  
Blood Vessel ◽  
Drug Concentration ◽  
Tumor Size ◽  
Drug Transport ◽  
Tumor Tissue ◽  
Transport Model ◽  
Temporal Structure ◽  
Drug Distribution ◽  
Tumor Vasculature

AbstractThe delivery of adequate concentration of anticancer drugs to tumor site is critical to achieve effective therapeutic treatment, but it is challenging to experimentally observe drug transport and investigate the spatial distribution of the drug in tumor microenvironment. In this study, we investigated the drug transport from a blood vessel to tumor tissue, and explored the effect of tumor size, tumor numbers and positioning on drug concentration distribution using a numerical method in combination with a microfluidic Tumor-Vasculature-on-a-Chip (TVOC) model. The TVOC model is composed of a vessel channel, a tumor channel sandwiched with a porous membrane. A species transport model based on computational fluid dynamics was adapted to investigate drug transport. The numerical simulation was firstly validated using experimental data, and then used to analyse the spatial-temporal structure of the flow, and to investigate the effect of tumor size and positioning on drug transport and drug concentration heterogeneity. We found the drug concentration surrounding the tumor is highly heterogeneous, with the most downstream point the most difficult for drugs to transport and the nearest point to the blood vessel the easiest. Moreover, tumor size and positioning contribute significantly to this drug concentration heterogeneity on tumor surface, which is dramatically augmented in large and downstream-positioned tumors. These studies established the relationship between solid tumor size/positioning and drug concentration heterogeneity in the tumor microenvironment, which could help to understand heterogenous drug distribution in tumor microenvironment.

scholarly journals Ex vivo toxicological evaluation of experimental anticancer gold(i) complexes with lansoprazole-type ligands

2019 ◽  
Vol 8 (6) ◽  
pp. 885-895
Author(s):  
Natalia Estrada-Ortiz ◽  
Elena Lopez-Gonzales ◽  
Ben Woods ◽  
Stefan Stürup ◽  
Inge A. M. de Graaf ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Ex Vivo ◽  
Gold Complex ◽  
Ex Vivo Model ◽  
Toxicological Evaluation ◽  
Anticancer Compounds ◽  
Kidney Slices ◽  
Icp Ms ◽  
Gold Compounds ◽  
Liver And Kidney

Abstract Gold-based compounds are of great interest in the field of medicinal chemistry as novel therapeutic (anticancer) agents due to their peculiar reactivity and mechanisms of action with respect to organic drugs. Despite their promising pharmacological properties, the possible toxic effects of gold compounds need to be carefully evaluated in order to optimize their design and applicability. This study reports on the potential toxicity of three experimental gold-based anticancer compounds featuring lansoprazole ligands (1–3) studied in an ex vivo model, using rat precision cut kidney and liver slices (PCKS and PCLS, respectively). The results showed a different toxicity profile for the tested compounds, with the neutral complex 2 being the least toxic, even less toxic than cisplatin, followed by the cationic complex 1. The dinuclear cationic gold complex 3 was the most toxic in both liver and kidney slices. This result correlated with the metal uptake of the different compounds assessed by ICP-MS, where complex 3 showed the highest accumulation of gold in liver and kidney slices. Interestingly compound 1 showed the highest selectivity towards cancer cells compared to the healthy tissues. Histomorphology evaluation showed a similar pattern for all three Au(i) complexes, where the distal tubular cells suffered the most extensive damage, in contrast to the damage in the proximal tubules induced by cisplatin. The binding of representative gold compounds with the model ubiquitin was also studied by ESI-MS, showing that after 24 h incubation only ‘naked’ Au ions were bound to the protein following ligands’ loss. The mRNA expression of stress response genes appeared to be similar for both evaluated organs, suggesting oxidative stress as the possible mechanism of toxicity. The obtained results open new perspectives towards the design and testing of bifunctional gold complexes with chemotherapeutic applications.

scholarly journals Microfluidic modelling of the tumor microenvironment for anti-cancer drug development

Lab on a Chip ◽  
2019 ◽  
Vol 19 (3) ◽  
pp. 369-386 ◽  
Author(s):  
Menglin Shang ◽  
Ren Hao Soon ◽  
Chwee Teck Lim ◽  
Bee Luan Khoo ◽  
Jongyoon Han
Keyword(s):  
Tumor Microenvironment ◽  
Drug Development ◽  
Tumor Model ◽  
Cancer Drug ◽  
Microfluidic Systems ◽  
Anti Cancer

Microfluidic tumor model has the unique advantage of recapitulating tumor microenvironment in a comparatively easier and representative fashion. In this review, we aim to focus more on the possibility of generating clinically actionable information from these microfluidic systems, not just scientific insight.

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