The Influence of Ozone on Tumor Tissue in Comparison with Healthy Tissue (in vitro)

1990 ◽  
Vol 12 (1) ◽  
pp. 65-72 ◽  
Author(s):  
J. WashüTtl ◽  
R. Viebahn ◽  
I. Steiner
Keyword(s):  
Tumor Tissue ◽  
Healthy Tissue

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 ROS-triggered self-accelerating drug release nanosystem with charge conversion for enhanced cancer therapy

2020 ◽  
Author(s):  
Xinyi Zhang ◽  
Tiantian Zhu ◽  
Yaxin Miao ◽  
Lu Zhou ◽  
Weifang Zhang
Keyword(s):  
Drug Release ◽  
Tumor Tissue ◽  
Anticancer Therapy ◽  
Cell Uptake ◽  
Oxygen Species ◽  
Anticancer Drug Delivery ◽  
Tocopheryl Succinate ◽  
Delivery Platform

Abstract Background: The enhancement tumor retention and of cellular uptake of drugs are important factors in maximizing anticancer therapy and minimizing side effects of encapsulated drugs. Herein, a delivery nanoplatform with a pH-triggered charge-reversal capability and self-amplifiable reactive oxygen species (ROS) level inducing drug release pattern was constructed by encapsulating doxorubicin (DOX) in pH/ROS-responsive polymeric micelle.Results: The surface charge of this system can be converted from negative to positive for enhanced tumor cell uptake in response to the weakly acidic tumor tissue. In addition, methionine-based system was dissociated in a ROS-rich intracellular environment, resulting in a phase transition and the release of DOX. Then, the exposed α-tocopheryl succinate (α-TOS) segments can be capable of producing ROS, which further induced the self-amplifiable disassembly of the micelles and drug release. Conclusions: We confirmed efficient DOX delivery into cancer cells, upregulation of tumoral ROS level and induction of the apoptotic capability in vitro. The system exhibited outstanding tumor inhibition capability in vivo, indicating that dual stimuli nanosytem would be great potential as an anticancer drug delivery platform.

Synthesis and distribution of cytokeratins in healthy and ulcerated bovine claw epidermis

2001 ◽  
Vol 68 (4) ◽  
pp. 525-537 ◽  
Author(s):  
KAY A. K. HENDRY ◽  
AMANDA J. MACCALLUM ◽  
CHRISTOPHER H. KNIGHT ◽  
COLIN J. WILDE
Keyword(s):  
Protein Synthesis ◽  
Detrimental Effect ◽  
Healthy Tissue ◽  
Amino Acid Incorporation ◽  
Keratinocyte Proliferation ◽  
Abnormal Distribution ◽  
Acid Incorporation ◽  
Dairy Animals ◽  
Dimensional Electrophoresis

Keratinization of the epidermal cells of the bovine claw generates the horn that gives the tissue its mechanical strength. Disruption of keratinization is likely to have a detrimental effect on the strength and integrity of the horn, and could lead to solar lesions and lameness. As part of a wider investigation of the cell biological causes of lameness in dairy animals, we have compared keratin synthesis and distribution in healthy bovine claw tissue with those in hooves with solar ulcers. Protein synthesis was measured by [35S]-labelled amino acid incorporation in claw tissue explant cultures. [35S]-labelled protein synthesis was higher in tissue from diseased claws than in healthy claws, and highest at the ulcer site. The identity of proteins synthesised in vitro did not differ between healthy and diseased tissue. DNA synthesis indicative of cell proliferation was also elevated in diseased tissue. Immunoblotting after one- or two-dimensional electrophoresis showed cytokeratins (CK) 4, 5/6, 10 and 14 to be amongst those expressed in healthy claw tissue. The relative abundance of these keratins was not altered in healthy regions of ulcerated hooves, nor at the ulcer site, but CK16, not usually found in healthy tissue, was detected in the sole of diseased claws. CK5/6 and CK14 were shown by immunohistochemistry to be present in the basal epidermis of healthy tissue, whereas CK10 was found in supra-basal layers. In healthy tissue from ulcerated claws, this distribution was unaltered, but at the site of solar ulcers, CK5/6 and CK14 were each found in both basal and supra-basal epidermis. The study suggests that solar ulceration of the bovine claw is not associated with gross alteration in the keratin composition of the tissue, but causes abnormal distribution of cytokeratins, perhaps as a result of loss of positional cues from the basement membrane. Ulceration did, however, stimulate cell repair involving epidermal protein synthesis (including keratins), and keratinocyte proliferation.

scholarly journals Fluorescence Tumor-Imaging Using a Thermo-Responsive Molecule with an Emissive Aminoquinoline Derivative

Nanomaterials ◽  
2018 ◽  
Vol 8 (10) ◽  
pp. 782 ◽  
Author(s):  
Takeru Araki ◽  
Yasufumi Fuchi ◽  
Shuhei Murayama ◽  
Ryoma Shiraishi ◽  
Tokimi Oyama ◽  
...  
Keyword(s):  
Cloud Point ◽  
Intravenous Administration ◽  
Tumor Tissue ◽  
Tumor Imaging ◽  
Fluorescence Probe ◽  
Local Heat ◽  
Solution Temperature ◽  
Lcst Behavior

We synthesized (2,4-trifluoromethyl-7-N-bis(2,5,8,11-tetraoxatridecane-13-yl)-aminoquinoline) TFMAQ-diEg4, an emissive aminoquinoline derivative that incorporated two tetraethyleneglycol chains into an amino group. TFMAQ-diEg4 showed fluorescence and thermo-responsive properties accompanied by a lower critical solution temperature (LCST), due to the introduction of the oligoethylene glycol chain. This thermo-responsive LCST behavior occurred at the border of a cloud point. Below and above the cloud point, self-assemblies of 6-7-nm nanoparticles and ~2000-nm microparticles were observed, in vitro. In addition, TFMAQ-diEg4 showed a high solubility, over 20 mM for aqueous solution, in vivo, which not only prevented thrombosis but also allowed various examinations, such as single intravenous administration and intravenous drips. Intravenous administration of TFMAQ-diEg4, to tumor-bearing, mice led to the accumulation of the molecule in the tumor tissue, as observed by fluorescence imaging. A subset of mice was treated with local heat around their tumor tissue and an intravenous drip of TFMAQ-diEg4, which led to a high intensity of TFMAQ-diEg4 emission within the tumor tissue. Therefore, we revealed that TFMAQ-diEg4 was useful as a fluorescence probe with thermo-responsive properties.

scholarly journals Human Tumor Tissue-Based 3D In Vitro Invasion Assays

2018 ◽  
pp. 213-221 ◽  
Author(s):  
Pirjo Åström ◽  
Ritva Heljasvaara ◽  
Pia Nyberg ◽  
Ahmed Al-Samadi ◽  
Tuula Salo
Keyword(s):  
Tumor Tissue ◽  
Human Tumor ◽  
In Vitro Invasion ◽  
Invasion Assays

scholarly journals 4081 Quantifying pH buffering capacity and kinetics of tumor and healthy tissue to understand and exploit differences in biology

2020 ◽  
Vol 4 (s1) ◽  
pp. 15-15
Author(s):  
A. Colleen Crouch ◽  
Emily A. Thompson ◽  
Mark D. Pagel ◽  
Erik N.K. Cressman
Keyword(s):  
Tumor Tissue ◽  
Ex Vivo ◽  
Buffering Capacity ◽  
The Body ◽  
Healthy Tissue ◽  
Buffer System ◽  
Bicarbonate Buffer ◽  
Ph Buffering ◽  
Acidocest Mri

OBJECTIVES/GOALS: The purpose of this work is to investigate natural buffering capacity of liver tissue and tumors, to understand and exploit differences for therapy. Using this work, we will determine the concentrations of reagents (acids or bases) used in ablation treatment to optimize treatment by increasing tumor toxicity and minimizing healthy tissue toxicity. METHODS/STUDY POPULATION: For this preliminary study, two methods will be used: benchtop pH experiments ex vivo and non-invasive imaging using acidoCEST MRI in vivo. For ex vivo, two types of tissues will be tested: non-cancerous liver and tumor tissue from HepG2 inoculated mice (n = 10). After mice are euthanized, pH will be measured in tissue homogenates at baseline and then the homogenates will be placed in either acidic (acetic acid) or basic (sodium hydroxide) solutions with varied concentrations (0.5–10M) and time recorded until pH returns to baseline. For in vivo imaging, Mia PaCA-2 flank model mice (n = 10) will be imaged with acidoCEST MRI to quantify pH at baseline. Mice will then be injected intratumorally with (up to 100 μL of) acid or base at increasing concentrations and imaged to quantify pH changes in the tumor. RESULTS/ANTICIPATED RESULTS: For this study, buffering capacity is defined as the concentration threshold for which tissue can buffer pH back to within normal range. Non-cancerous tissue is likely to buffer a wider range of concentrations compared to tumor tissue. From the benchtop experiment, comparison of time-to-buffer will be made for each concentration of acid/base for the two tissue types. AcidoCEST MRI will provide in vivo buffering capacity and potentially demonstrate tumor heterogeneity of buffering capacity. For both experiments, a pH vs. concentration curve for the two tissue types will allow for comparison of ex vivo to in vivo experiments, which will differentiate contributions of local tissue buffering capacity from the full body’s natural bicarbonate buffer system that depends on respiration and blood flow. DISCUSSION/SIGNIFICANCE OF IMPACT: The pH of the body must be maintained within a narrow range. With cancer, impairment in regulation of tumor metabolism causes acidosis, lowering extracellular pH in tumors. It remains unclear if pH plays a role in local recurrence or tumor toxicity. This work will determine if acidoCEST MRI can measure deliberate alteration of pH and how this change affects biology.

Plasminogen Activator (PA) Activity In Metastatic Cells: An Amidolytic Approach

1981 ◽  
Author(s):  
D Coen ◽  
A Bini ◽  
G Balconi ◽  
F Delaini ◽  
L Mussoni ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Fibrinolytic Activity ◽  
Tumor Tissue ◽  
Cultured Cells ◽  
Cell Extracts ◽  
Mechanical Disruption ◽  
Metastatic Cells ◽  
Triton X ◽  
Selection Of

It has been proposed that fibrinolytic activity can play an important role in the process of metastasis formation. Nevertheless, it is not yet clear in which phase of the tumor growth and dissemination this activity is involved. We measured the fibrinolytic activity of cells from primary tumor and metastatic nodules of 3LL, an i.m. implanted murine tumor which selectively metastasizes to the lungs. Tumor cells have been studied both immediately after mechanical disruption of tumor tissue and after in vitro culturing to confluence. Their P.A. activity was tested by an amidolytic assay in which cells were incubated with purified plasminogen (3CU/ml) and 4mM S-2251 (Kabi Diagnostica, Stockholm, Sweden), a plasmin specific chromogenic substrate. After 3 hour incubation at 37°C, the reaction was stopped with acetic acid and absorbance read at 405 nm.Cells from the primary tumor and metastatic nodules showed a similar fibrinolytic activity, which was in both cases in- increased 3 to 4 fold in cell extracts obtained after preincubation with TRITON X-100. A dose-response curve plotted with increasing urokinase concentrations showed a parallel course. This data suggests that, in the 3LL model, PA activity is not one of the properties characterizing the selection of metastatic cells.On the other hand,cultured cells presented consistently higher levels of PA than their native counterparts, suggesting that adhesion of cells in culture may stimulate PA production or, alternatively, that cultured cells are a selected population in comparison to the overall number of native cells.

scholarly journals MicroRNA-223-3p inhibits human bladder cancer cell migration and invasion

Tumor Biology ◽  
2017 ◽  
Vol 39 (2) ◽  
pp. 101042831769167 ◽  
Author(s):  
Ju Guo ◽  
Runfu Cao ◽  
Xingwei Yu ◽  
Zewen Xiao ◽  
Zhiwen Chen
Keyword(s):  
Nuclear Receptor ◽  
Bladder Carcinoma ◽  
Messenger Rna ◽  
Tumor Tissue ◽  
Protein Translation ◽  
Carcinoma Cells ◽  
Migration And Invasion ◽  
Nuclear Receptor Coactivator ◽  
Bladder Carcinoma Cells

The regulation of initiation and progression during carcinogenesis of bladder carcinoma is not completely elucidated. Dysregulation of microRNAs has been detected to play critical roles in the development of various cancers, including bladder carcinoma, whereas the involvement of miR-223-3p in the tumorigenesis of bladder carcinoma has not been studied. Here, we show that significantly higher levels of nuclear receptor coactivator 1 and significantly lower levels of miR-223-3p were detected in bladder carcinoma tissue, compared to the adjacent non-tumor tissue. In addition, the levels of nuclear receptor coactivator 1 and miR-223-3p were inversely correlated. Moreover, low miR-223-3p levels in bladder carcinoma specimens were associated with poor prognosis. In vitro, depletion of miR-223-3p increased bladder carcinoma cell invasion, which was abolished by overexpression of nuclear receptor coactivator 1. Bioinformatics studies demonstrate that miR-223-3p may bind to the 3′-UTR of nuclear receptor coactivator 1 messenger RNA to inhibit its protein translation in bladder carcinoma cells. Together, our study highlights miR-223-3p as a previously unrecognized microRNA that inhibits bladder carcinoma invasiveness via nuclear receptor coactivator 1, and this finding may be important for developing innovative therapeutic targets in treating bladder carcinoma.

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