scholarly journals Thermochemical Ablation: A Novel Technique for Solid Tumor Therapy

2009 ◽  
Vol 3 (2) ◽  
Author(s):  
M. Shenoi ◽  
E. Cressman
Keyword(s):  
Solid Tumors ◽  
Tumor Tissue ◽  
Tumor Therapy ◽  
Exothermic Reaction ◽  
Palliative Therapy ◽  
Distal Portion ◽  
Tissue Destruction ◽  
Prototype Device

To overcome the limitations of existing ablation techniques, we propose a novel combinatorial approach that would utilize the thermal and chemical destructive effects of exothermic chemical reactions, such as an acid/base neutralization reaction, to treat solid tumors. Thermochemical ablation is a potential technique for percutaneous probe-based tumor therapy. It involves simultaneous intratumoral delivery of multiple reagents resulting in thermal energy released by an exothermic reaction to ablate tumor tissue with concurrent generation of a hyperosmolar byproduct that could accentuate tumor destruction. Besides the benefit of synergistic thermal and chemical effects for tumor tissue destruction, this technique is potentially highly cost-effective, easy to implement, and able to treat larger sized tumors. Our hypothesis is that thermochemical ablation can create an evenly distributed zone of coagulation in tumor tissue without systemic toxicity. A prototype device assembled using off-the-shelf components is being investigated in our lab for concurrent intraparenchymal delivery of an acid and a base. The distal portion of the multi-lumen device allows for passive mixing of the reagents before entering the tissue. The prototype device also satisfies other desirable design criteria such as rigidity to penetrate body tissue, reduced diameter, chemical stability to reagents, etc. However, the device can be improved upon by incorporating additional characteristics such as optimized imaging characteristic for real-time visualization and localization within tumor tissue, MRI compatibility, thermal insulation, improved mixing at the tip, etc. Our lab is currently working on improving the design of the infusion device as well as assessing the feasibility of the thermochemical ablation technique in vitro and in vivo. While currently being targeted conservatively for palliative therapy of unresectable or late-stage aggressive malignancies such as hepatocellular carcinoma, thermochemical ablation has potential use in the therapy of a majority of solid tumors such as breast cancer, lung cancer, prostate cancer, renal cancer, sarcomas, etc.

scholarly journals Solid tumor therapy by selectively targeting stromal endothelial cells

2016 ◽  
Vol 113 (28) ◽  
pp. E4079-E4087 ◽  
Author(s):  
Shihui Liu ◽  
Jie Liu ◽  
Qian Ma ◽  
Liu Cao ◽  
Rasem J. Fattah ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Solid Tumors ◽  
Tumor Therapy ◽  
Loss Of Function ◽  
Anthrax Lethal Toxin ◽  
Tumor Endothelial Cells ◽  
Wide Range ◽  
Tumor Endothelium

Engineered tumor-targeted anthrax lethal toxin proteins have been shown to strongly suppress growth of solid tumors in mice. These toxins work through the native toxin receptors tumor endothelium marker-8 and capillary morphogenesis protein-2 (CMG2), which, in other contexts, have been described as markers of tumor endothelium. We found that neither receptor is required for tumor growth. We further demonstrate that tumor cells, which are resistant to the toxin when grown in vitro, become highly sensitive when implanted in mice. Using a range of tissue-specific loss-of-function and gain-of-function genetic models, we determined that this in vivo toxin sensitivity requires CMG2 expression on host-derived tumor endothelial cells. Notably, engineered toxins were shown to suppress the proliferation of isolated tumor endothelial cells. Finally, we demonstrate that administering an immunosuppressive regimen allows animals to receive multiple toxin dosages and thereby produces a strong and durable antitumor effect. The ability to give repeated doses of toxins, coupled with the specific targeting of tumor endothelial cells, suggests that our strategy should be efficacious for a wide range of solid tumors.

scholarly journals Combination of AAV-CCL19 and GPC3 CAR-T Cells in the Treatment of Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Min Meng ◽  
Yi-chen Wu
Keyword(s):  
T Cells ◽  
T Cell ◽  
Solid Tumors ◽  
Tumor Tissue ◽  
Malignant Tumors ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T

Background. Chimeric antigen receptor-modified T cell (CAR-T) therapy has great potential for treating malignant tumors, especially hematological malignancies. However, the therapeutic effect of solid tumors is limited. One of the most important factors is the homing of CAR-T cells to tumor tissues in vivo. Method. a recombinant adeno-associated virus 2 (AAV2) subtype carrying the CCL19 gene was used to pretreat the tumor before the Glypican-3 (GPC3) CAR-T treatment. The tumor tissue continuously expressed CCL19 and analyzed the tumor-suppressive effect of AAV-CCL19 on GPC3 CAR-T by in vitro and in vivo experiments. Result. Under the chemotaxis of CCL19, CAR-T cells had a significant increase in the degree of tumor tissue infiltration; also, the antitumor effect in vitro was significantly enhanced. AAV-CCL19 combined with GPC3 CAR-T significantly increased the survival time of mice. The aforementioned results showed that the combination of AAV-CCL19 and GPC3 CAR-T cells effectively increased the ability of CAR-T cells to go home into the tumor tissue, making the CAR-T cell treatment more effective. Conclusion. This study is expected to solve the dilemma in treating CAR-T cell solid tumors and achieve better clinical results.

scholarly journals Co-expression of IL-7 and PH20 Promote anti-GPC3 CAR-T Tumor Suppressor Activity in Vivo and in Vitro

2020 ◽  
Author(s):  
Qian Liu ◽  
Cixiao Wang ◽  
Zeyou Jiang ◽  
Su-yang Yue
Keyword(s):  
T Cells ◽  
Solid Tumors ◽  
Hematological Malignancies ◽  
Tumor Tissue ◽  
Suppressor Activity ◽  
Car T Cells ◽  
Car T ◽  
Tumor Suppressor Activity

Abstract While CAR-T therapy has successfully treated hematological malignancies, it has proved sub-optimal for solid tumors. The main limitation is the inability of CAR-T cells to infiltrate and then proliferate within tumors. In this study, we co-expressed IL-7 and PH20, a type of hyaluronidase, with CAR targeting GPC3 (G3CAR-7×20) to address these issues. We found (G3CAR-7×20) exhibited better proliferation in vivo and in vitro than G3CAR, reduced the level of apoptosis after stimulation by tumor cells, and maintained the memory phenotype of CAR-T cells. G3CAR-7×20 also increased the ability of CAR-T cells to infiltrate tumor tissue. G3CAR-7×20 may significantly enhance the efficacy of CAR-T cells in solid tumors.

scholarly journals Sonazoid-Conjugated Natural Killer Cells for Tumor Therapy and Real-Time Visualization by Ultrasound Imaging

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1689
Author(s):  
Hyeong-Woo Song ◽  
Han-Sol Lee ◽  
Seok-Jae Kim ◽  
Ho Yong Kim ◽  
You Hee Choi ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Real Time ◽  
Solid Tumors ◽  
Ultrasound Imaging ◽  
Tumor Therapy ◽  
Real Time Control ◽  
Time Control

Various cell therapy strategies, including chimeric antigen receptor-expressing T or natural killer (NK) cells and cell-mediated drug delivery, have been developed for tumor eradication. However, the efficiency of these strategies against solid tumors remains unclear. We hypothesized that real-time control and visualization of therapeutic cells, such as NK cells, would improve their therapeutic efficacy against solid tumors. In this study, we engineered Sonazoid microbubble-conjugated NK (NK_Sona) cells and demonstrated that they were detectable by ultrasound imaging in real-time and maintained their functions. The Sonazoid microbubbles on the cell membrane did not affect the cytotoxicity and viability of the NK cells in vitro. Additionally, the NK_Sona cells could be visualized by ultrasound imaging and inhibited tumor growth in vivo. Taken together, our findings demonstrate the feasibility of this new approach in the use of therapeutic cells, such as NK cells, against solid tumors.

Internal and External Triggering Mechanism of “Smart” Nanoparticle-Based DDSs in Targeted Tumor Therapy

2018 ◽  
Vol 24 (15) ◽  
pp. 1639-1651 ◽  
Author(s):  
Xian-ling Qian ◽  
Jun Li ◽  
Ran Wei ◽  
Hui Lin ◽  
Li-xia Xiong
Keyword(s):  
Targeted Delivery ◽  
Tumor Therapy ◽  
Burst Release ◽  
Tumor Site ◽  
Chemotherapeutic Drugs ◽  
Triggering Mechanism ◽  
Triggering Factors ◽  
Or Genes

Background: Anticancer chemotherapeutics have a lot of problems via conventional Drug Delivery Systems (DDSs), including non-specificity, burst release, severe side-effects, and damage to normal cells. Owing to its potential to circumventing these problems, nanotechnology has gained increasing attention in targeted tumor therapy. Chemotherapeutic drugs or genes encapsulated in nanoparticles could be used to target therapies to the tumor site in three ways: “passive”, “active”, and “smart” targeting. Objective: To summarize the mechanisms of various internal and external “smart” stimulating factors on the basis of findings from in vivo and in vitro studies. Method: A thorough search of PubMed was conducted in order to identify the majority of trials, studies and novel articles related to the subject. Results: Activated by internal triggering factors (pH, redox, enzyme, hypoxia, etc.) or external triggering factors (temperature, light of different wavelengths, ultrasound, magnetic fields, etc.), “smart” DDSs exhibit targeted delivery to the tumor site, and controlled release of chemotherapeutic drugs or genes. Conclusion: In this review article, we summarize and classify the internal and external triggering mechanism of “smart” nanoparticle-based DDSs in targeted tumor therapy, and the most recent research advances are illustrated for better understanding.

scholarly journals Diaphanous related formin 3 knockdown suppresses cell proliferation and metastasis of osteosarcoma cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zehua Zhang ◽  
Fei Dai ◽  
Fei Luo ◽  
Wenjie Wu ◽  
Shuai Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Therapy ◽  
Disease Free Survival ◽  
Tumor Stage ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Proliferation And Metastasis ◽  
New Biomarkers

AbstractOsteosarcoma is a malignant osteoblastic tumor that can gravely endanger the lives and health of children and adolescents. Therefore, there is an urgent need to explore new biomarkers for osteosarcoma and determine new targeted therapies to improve the efficacy of osteosarcoma treatment. Diaphanous related formin 3 (DIAPH3) promotes tumorigenesis in hepatocellular carcinoma and lung adenocarcinoma, suggesting that DIAPH3 may be a target for tumor therapy. To date, there have been no reports on the function of DIAPH3 in osteosarcoma. DIAPH3 protein expression in osteosarcoma tissues and healthy bone tissues adjacent to cancer cells was examined by immunohistochemical staining. DIAPH3 mRNA expression correlates with overall survival and reduced disease-free survival. DIAPH3 protein is upregulated in osteosarcoma tissues, and its expression is significantly associated with tumor size, tumor stage, node metastasis, and distant metastasis. Functional in vitro experiments revealed that DIAPH3 knockdown suppressed cell proliferation and suppressed cell migration and invasion of osteosarcoma cell lines MG-63 and HOS. Functional experiments demonstrated that DIAPH3 knockdown inhibited subcutaneous tumor growth and lung metastasis in vivo. In conclusion, DIAPH3 expression can predict the clinical outcome of osteosarcoma. In addition, DIAPH3 is involved in the proliferation and metastasis of osteosarcoma, and as such, DIAPH3 may be a potential therapeutic target for osteosarcoma.

scholarly journals Topotecan-loaded thermosensitive nanocargo for tumor therapy: In vitro and in vivo analyses

2021 ◽  
pp. 120871
Author(s):  
Zhiyong Zhang ◽  
Pan Yan ◽  
Yan Zhao ◽  
Mudan Ren ◽  
Yarui Li ◽  
...  
Keyword(s):  
Tumor Therapy

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.

scholarly journals Tumor-Targeting Peptides Search Strategy for the Delivery of Therapeutic and Diagnostic Molecules to Tumor Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 314
Author(s):  
Maria D. Dmitrieva ◽  
Anna A. Voitova ◽  
Maya A. Dymova ◽  
Vladimir A. Richter ◽  
Elena V. Kuligina
Keyword(s):  
Phage Display ◽  
Cell Sorting ◽  
Targeted Delivery ◽  
Tumor Targeting ◽  
Search Strategy ◽  
Tumor Therapy ◽  
Therapeutic Agents ◽  
Phage Libraries

Background: The combination of the unique properties of cancer cells makes it possible to find specific ligands that interact directly with the tumor, and to conduct targeted tumor therapy. Phage display is one of the most common methods for searching for specific ligands. Bacteriophages display peptides, and the peptides themselves can be used as targeting molecules for the delivery of diagnostic and therapeutic agents. Phage display can be performed both in vitro and in vivo. Moreover, it is possible to carry out the phage display on cells pre-enriched for a certain tumor marker, for example, CD44 and CD133. Methods: For this work we used several methods, such as phage display, sequencing, cell sorting, immunocytochemistry, phage titration. Results: We performed phage display using different screening systems (in vitro and in vivo), different phage libraries (Ph.D-7, Ph.D-12, Ph.D-C7C) on CD44+/CD133+ and without enrichment U-87 MG cells. The binding efficiency of bacteriophages displayed tumor-targeting peptides on U-87 MG cells was compared in vitro. We also conducted a comparative analysis in vivo of the specificity of the accumulation of selected bacteriophages in the tumor and in the control organs (liver, brain, kidney and lungs). Conclusions: The screening in vivo of linear phage peptide libraries for glioblastoma was the most effective strategy for obtaining tumor-targeting peptides providing targeted delivery of diagnostic and therapeutic agents to glioblastoma.

Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor

1994 ◽  
Vol 266 (6) ◽  
pp. L593-L611 ◽  
Author(s):  
M. D. Evans ◽  
W. A. Pryor
Keyword(s):  
Cigarette Smoke ◽  
Proteinase Inhibitor ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Lung Lavage ◽  
Tissue Destruction ◽  
Phagocytic Cells ◽  
Lung Fluid

The proteinase-antiproteinase theory for the pathogenesis of emphysema proposes that the connective tissue destruction associated with emphysema arises from excessive proteinase activity in the lower respiratory tract. For this reason, the relative activities of neutrophil elastase and alpha 1-proteinase inhibitor (alpha 1-PI) are considered important. Most emphysema is observed in smokers; therefore, alpha 1-PI has been studied as a target for smoke-induced damage. Damage to alpha 1-PI in lung fluid could occur by several mechanisms involving species delivered to the lung by cigarette smoke and/or stimulated inflammatory cells. Oxidative damage to alpha 1-PI has received particular attention, since both cigarette smoke and inflammatory cells are rich sources of oxidants. In this article we review almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 1-PI at the molecular and functional levels.

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