Ultrasound Biomicroscopy of Cancer Therapy Effects: Correlation between Light and Electron Microscopy, and a New Non-Invasive Ultrasound Imaging Method for Detecting Apoptosis

2000 ◽  
Vol 6 (S2) ◽  
pp. 1014-1015
Author(s):  
G.J. Czarnota ◽  
M.C. Kolios ◽  
Y.M. Heng ◽  
K. Devaraj ◽  
C. Tam ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Ultrasound Imaging ◽  
Light And Electron Microscopy ◽  
Ultrasound Biomicroscopy ◽  
Response To Treatment ◽  
Imaging Method ◽  
High Frequency Ultrasound

We have discovered that high-frequency ultrasound imaging, or ultrasound biomicroscopy, can be used to detect apoptosis in a number of experimental systems. We have shown that such detection with 30-40 MHz ultrasound is possible using cells in an in vitro system (AML-3 leukemia cells) made to undergo apoptosis in response to treatment with a variety of cancer killing chemotherapeutic drugs. We have shown that ultrasound biomicroscopy can also detect programmed cell death in tissues made to undergo apoptosis in response to photodynamic therapy, currently an experimental cancer treating regimen. Lastly, we have shown that this ultrasound imaging approach works in vivo, using living animals where apoptosis has been induced similarly using photodynamic therapy. Specifically, apoptotic cells and regions of apoptosis in tissues exhibit up to a 36-fold increase in ultrasound backscatter intensity permitting this type of cell death to be readily discriminated from surrounding viable tissue.

scholarly journals Ultrasound imaging of apoptosis: high-resolution non-invasive monitoring of programmed cell death in vitro, in situ and in vivo

1999 ◽  
Vol 81 (3) ◽  
pp. 520-527 ◽  
Author(s):  
G J Czarnota ◽  
M C Kolios ◽  
J Abraham ◽  
M Portnoy ◽  
F P Ottensmeyer ◽  
...  
Keyword(s):  
Cell Death ◽  
High Resolution ◽  
Programmed Cell Death ◽  
Ultrasound Imaging ◽  
Invasive Monitoring ◽  
Non Invasive

Preclinical photodynamic therapy research in Spain 3: Localization of photosensitizers and mechanisms of cell deathin vitro

2009 ◽  
Vol 13 (04n05) ◽  
pp. 544-551 ◽  
Author(s):  
Magdalena Cañete ◽  
Juan C. Stockert ◽  
Angeles Villanueva
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Cell Cultures ◽  
Cellular Localization ◽  
Cell Damage ◽  
Therapeutic Modality ◽  
Action Mechanisms ◽  
Cell Death Mechanisms

Photodynamic therapy (PDT) is a subject of increasing biomedical research and represents a very promising therapeutic modality for palliative or even curative treatment of some superficial or endoscopically accessible tumors. In addition to the first photosensitizers (PSs) applied (hematoporphyrin-based drugs), second generation PSs with improved photophysical and photobiological properties are now studied using cell cultures, experimental tumors and clinical trials. On the other hand, there is a growing interest in the analysis of cell death mechanisms by apoptosis, which is especially relevant in oncology, because many anticancer drugs work, at least in part, by triggering apoptosis in neoplastic cells both in vitro and in vivo. The evaluation of cell death mechanisms is an important parameter to determine the efficacy and the potential toxicity of a treatment, allowing better adjustment of protocol. Using cell cultures, our research team has studied the mechanisms of cell damage and death implicated in the photodynamic processes, as well as the relationship between the cellular localization of the PS and the organelle damage during photosensitization. The results obtained in our laboratory provide a deeper understanding on the action mechanisms that lead to cell inactivation by PDT, and also allow selection of PSs with higher potential for clinical application than those currently in use.

scholarly journals Combination of apoptin with photodynamic therapy induces nasopharyngeal carcinoma cell death in vitro and in vivo

2012 ◽  
Vol 28 (6) ◽  
pp. 2077-2082 ◽  
Author(s):  
XIAOYONG FANG ◽  
PING WU ◽  
JINYUN LI ◽  
LIN QI ◽  
YAOYUN TANG ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Nasopharyngeal Carcinoma ◽  
Carcinoma Cell ◽  
Nasopharyngeal Carcinoma Cell

scholarly journals Conventional frequency ultrasound detection of tumor response in vivo to cancer treatment administration

2021 ◽  
Author(s):  
Naum Papanicolau
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Structural Changes ◽  
Apoptotic Cell ◽  
High Frequency Ultrasound ◽  
Patient Response ◽  
Tumor Morphology ◽  
Frequency Ultrasound

Current methods employed to evaluate patient response to cancer therapy are typically invasive requiring examination of excised tissue. The development of a non-invasive method of monitoring patient response to cancer therapy administration would potentiate clinical decisions permitting clinicians to adjust therapy regimens early in a treatment course based upon individual patient responses. It has been previously demonstrated that high frequency ultrasound is capable of reliably quantifying structural changes in tumor morphology in response to cancer therapies. Preliminary work has also indicated that ultrasound employed at clinically relevant frequencies (1-15 MHz) can detect apoptotic cell death using in vitro models. This thesis examines changes in tumor morphology in response to cancer therapy administration employing ultrasound at a clinically applicable frequency in a preclinical in vivo mouse model. The power spectrum of the radiofrequency data obtained from tumors was analyzed via linear regression spectroscopic analysis, as well as evaluating a statistical analysis of the amplitude distribution of the signal envelope. It is demonstrated here for the first time that 7 MHz ultrasound can detect apoptotic and other forms of cell death in vivo. A potential for a parametric imaging technique to visually represent analysis results is also demonstrated.

scholarly journals Induction of Immunogenic Cell Death by Photodynamic Therapy Mediated by Aluminum-Phthalocyanine in Nanoemulsion

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 196
Author(s):  
Mosar Corrêa Rodrigues ◽  
Wellington Tavares de Sousa Júnior ◽  
Thayná Mundim ◽  
Camilla Lepesqueur Costa Vale ◽  
Jaqueline Vaz de Oliveira ◽  
...  
Keyword(s):  
Cell Death ◽  
Photodynamic Therapy ◽  
Tumor Development ◽  
Light Dose ◽  
Target Cells ◽  
Immunogenic Cell Death ◽  
Aluminum Phthalocyanine ◽  
Direct Cytotoxicity

Photodynamic therapy (PDT) has been clinically employed to treat mainly superficial cancer, such as basal cell carcinoma. This approach can eliminate tumors by direct cytotoxicity, tumor ischemia, or by triggering an immune response against tumor cells. Among the immune-related mechanisms of PDT, the induction of immunogenic cell death (ICD) in target cells is to be cited. ICD is an apoptosis modality distinguished by the emission of damage-associated molecular patterns (DAMP). Therefore, this study aimed to analyze the immunogenicity of CT26 and 4T1 treated with PDT mediated by aluminum-phthalocyanine in nanoemulsion (PDT-AlPc-NE). Different PDT-AlPc-NE protocols with varying doses of energy and AlPc concentrations were tested. The death mechanism and the emission of DAMPs–CRT, HSP70, HSP90, HMGB1, and IL-1β–were analyzed in cells treated in vitro with PDT. Then, the immunogenicity of these cells was assessed in an in vivo vaccination-challenge model with BALB/c mice. CT26 and 4T1 cells treated in vitro with PDT mediated by AlPc IC50 and a light dose of 25 J/cm² exhibited the hallmarks of ICD, i.e., these cells died by apoptosis and exposed DAMPs. Mice injected with these IC50 PDT-treated cells showed, in comparison to the control, increased resistance to the development of tumors in a subsequent challenge with viable cells. Mice injected with 4T1 and CT26 cells treated with higher or lower concentrations of photosensitizer and light doses exhibited a significantly lower resistance to tumor development than those injected with IC50 PDT-treated cells. The results presented in this study suggest that both the photosensitizer concentration and light dose affect the immunogenicity of the PDT-treated cells. This event can affect the therapy outcomes in vivo.

27. Low Frequency Ultrasound Imaging of Apoptosis in Tumor Response: Non-Invasive Monitoring of Chemotherapy Effects

2018 ◽  
Author(s):  
Stephanie Zhou
Keyword(s):  
Cell Death ◽  
Ultrasound Imaging ◽  
Structural Changes ◽  
Imaging Techniques ◽  
Low Frequency ◽  
Acoustic Properties ◽  
High Frequency Ultrasound ◽  
Noninvasive Methods ◽  
Frequency Ultrasound

Due to the growing costs of chemotherapy, previous imaging techniques such as MRI or CT scans have become too time-consuming in the assessment of chemotherapy’s effects. With results generated about 2 weeks later, the patient is exposed to the negative side effects of these medications with the possibility that chemotherapy may not be improving their prognosis. Thus, ultrasound has become increasingly popular as a method to determine chemotherapy’s effect on tumors within 24 hours. Both low and high-frequency ultrasound are novel, noninvasive methods for detecting cell death based on changes in cell morphology. Condensation, fragmentation and alterations in the cell nucleus during apoptosis are linked to changes in the cell’s acoustic properties, as indicated by experimental evidence. In this study, quantitative ultrasound was used to follow responses of tumor models to chemotherapy in vivo. As studies have shown that structural changes can occur as early as 24 hours after treatment, ultrasound imaging was administered before and 24 hours after treatment. Changes in ultrasound parameters such as spectral slope, Y-intercept, and midband fit were analyzed relative to pretreatment control data and when compared to changes in the tumors seen through cell staining, changes consistent with cell death were observed.

scholarly journals Conventional frequency ultrasound detection of tumor response in vivo to cancer treatment administration

2021 ◽  
Author(s):  
Naum Papanicolau
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Structural Changes ◽  
Apoptotic Cell ◽  
High Frequency Ultrasound ◽  
Patient Response ◽  
Tumor Morphology ◽  
Frequency Ultrasound

Current methods employed to evaluate patient response to cancer therapy are typically invasive requiring examination of excised tissue. The development of a non-invasive method of monitoring patient response to cancer therapy administration would potentiate clinical decisions permitting clinicians to adjust therapy regimens early in a treatment course based upon individual patient responses. It has been previously demonstrated that high frequency ultrasound is capable of reliably quantifying structural changes in tumor morphology in response to cancer therapies. Preliminary work has also indicated that ultrasound employed at clinically relevant frequencies (1-15 MHz) can detect apoptotic cell death using in vitro models. This thesis examines changes in tumor morphology in response to cancer therapy administration employing ultrasound at a clinically applicable frequency in a preclinical in vivo mouse model. The power spectrum of the radiofrequency data obtained from tumors was analyzed via linear regression spectroscopic analysis, as well as evaluating a statistical analysis of the amplitude distribution of the signal envelope. It is demonstrated here for the first time that 7 MHz ultrasound can detect apoptotic and other forms of cell death in vivo. A potential for a parametric imaging technique to visually represent analysis results is also demonstrated.

scholarly journals TNF-α Triggers RIP1/FADD/Caspase-8-Mediated Apoptosis of Astrocytes and RIP3/MLKL-Mediated Necroptosis of Neurons Induced by Angiostrongylus cantonensis Infection

2021 ◽  
Author(s):  
Hongli Zhou ◽  
Minyu Zhou ◽  
Yue Hu ◽  
Yanin Limpanon ◽  
Yubin Ma ◽  
...  
Keyword(s):  
Cell Death ◽  
Enrichment Analysis ◽  
Angiostrongylus Cantonensis ◽  
Gene Set Enrichment Analysis ◽  
Caspase 8 ◽  
Cns Injury ◽  
Vitro Assay ◽  
Tnf Α

AbstractAngiostrongylus cantonensis (AC) can cause severe eosinophilic meningitis or encephalitis in non-permissive hosts accompanied by apoptosis and necroptosis of brain cells. However, the explicit underlying molecular basis of apoptosis and necroptosis upon AC infection has not yet been elucidated. To determine the specific pathways of apoptosis and necroptosis upon AC infection, gene set enrichment analysis (GSEA) and protein–protein interaction (PPI) analysis for gene expression microarray (accession number: GSE159486) of mouse brain infected by AC revealed that TNF-α likely played a central role in the apoptosis and necroptosis in the context of AC infection, which was further confirmed via an in vivo rescue assay after treating with TNF-α inhibitor. The signalling axes involved in apoptosis and necroptosis were investigated via immunoprecipitation and immunoblotting. Immunofluorescence was used to identify the specific cells that underwent apoptosis or necroptosis. The results showed that TNF-α induced apoptosis of astrocytes through the RIP1/FADD/Caspase-8 axis and induced necroptosis of neurons by the RIP3/MLKL signalling pathway. In addition, in vitro assay revealed that TNF-α secretion by microglia increased upon LSA stimulation and caused necroptosis of neurons. The present study provided the first evidence that TNF-α was secreted by microglia stimulated by AC infection, which caused cell death via parallel pathways of astrocyte apoptosis (mediated by the RIP1/FADD/caspase-8 axis) and neuron necroptosis (driven by the RIP3/MLKL complex). Our research comprehensively elucidated the mechanism of cell death after AC infection and provided new insight into targeting TNF-α signalling as a therapeutic strategy for CNS injury.

scholarly journals iPLA2β Contributes to ER Stress-Induced Apoptosis during Myocardial Ischemia/Reperfusion Injury

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1446
Author(s):  
Tingting Jin ◽  
Jun Lin ◽  
Yingchao Gong ◽  
Xukun Bi ◽  
Shasha Hu ◽  
...  
Keyword(s):  
Cell Death ◽  
Heart Disease ◽  
Myocardial Ischemia ◽  
Ischemic Heart Disease ◽  
Er Stress ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion ◽  
Induced Apoptosis

Both calcium-independent phospholipase A2 beta (iPLA2β) and endoplasmic reticulum (ER) stress regulate important pathophysiological processes including inflammation, calcium homeostasis and apoptosis. However, their roles in ischemic heart disease are poorly understood. Here, we show that the expression of iPLA2β is increased during myocardial ischemia/reperfusion (I/R) injury, concomitant with the induction of ER stress and the upregulation of cell death. We further show that the levels of iPLA2β in serum collected from acute myocardial infarction (AMI) patients and in samples collected from both in vivo and in vitro I/R injury models are significantly elevated. Further, iPLA2β knockout mice and siRNA mediated iPLA2β knockdown are employed to evaluate the ER stress and cell apoptosis during I/R injury. Additionally, cell surface protein biotinylation and immunofluorescence assays are used to trace and locate iPLA2β. Our data demonstrate the increase of iPLA2β augments ER stress and enhances cardiomyocyte apoptosis during I/R injury in vitro and in vivo. Inhibition of iPLA2β ameliorates ER stress and decreases cell death. Mechanistically, iPLA2β promotes ER stress and apoptosis by translocating to ER upon myocardial I/R injury. Together, our study suggests iPLA2β contributes to ER stress-induced apoptosis during myocardial I/R injury, which may serve as a potential therapeutic target against ischemic heart disease.

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