CLINICAL APPLICATIONS OF ELECTROCHEMOTHERAPY

2019 ◽  
Author(s):  
Gregor Serša
Keyword(s):  
Biomedical Applications ◽  
Liver Tumors ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Local Treatment ◽  
Industrial Applications ◽  
Interleukin 12 ◽  
Nice Guidelines ◽  
Or Gene

Electroporation has several biomedical and industrial applications. The biomedical applications are in the field of drug or gene delivery. Electrochemotherapy utilizes electroporation for the increased delivery of cytotoxic drugs like bleomycin or cisplatin into tumors. The use of electrochemotherapy has spread throughout Europe for the treatment of cutaneous tumors or metastases. It is in the NICE guidelines and is becoming standard ablative technique in treatment of cancer. The technological advancements have also enabled the use of electrochemotherapy for the treatment of deep seated tumors, such as soft tissue or liver tumors. Clinical studies demonstrate good effectiveness on fibrosarcomas, colorectal liver metastases and hepatocellular carcinoma. However, electrochemotherapy is a local treatment that also induces moderate local immune response. This so called “in situ vaccination” induced by electrochemotherapy can be exploited in combined treatment with immune checkpoint inhibitors or electrogene therapy with immunostimulating effect. Therefore, gene electrotransfer of plasmid coding for interleukin 12 (IL-12), in combination with electrochemotherapy could result in transformation of electrochemotherapy from local into systemic treatment. This is also of our current interest, and we are undertaking steps to bring this idea from preclinical into clinical testing.

Improvement of immune response after radiofrequency ablation in colorectal cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 102-102 ◽  
Author(s):  
Katia Lemdani ◽  
Nathalie Mignet ◽  
Johanne Seguin ◽  
Frederique Peschaud ◽  
Jean-François Emile ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Radiofrequency Ablation ◽  
T Lymphocytes ◽  
Immune Escape ◽  
Liver Tumors ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
T Cell Response

102 Background: Radiofrequency ablation (RFA) efficiency of liver tumors is compromised by high rates of relapse. Death of cancer cells by hyperthermia induced tumor antigen releasing, expression of danger signals that activate a specific T-cell response. This effect is ineffective to avoid recurrence. We propose to combine RFA with priming of a strong immune antitumor response as curative treatment of an aggressive colorectal cancer (CRC) in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor as primary lesion. In two distinct clinical situations, macroscopic or microscopic distant tumors were established as secondary lesions. The immune response was modulated by the injection, in the treated area, of a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting recruitment and maturation of dendritic cells. In mice with far large lesions, this strategy was combined with PD1checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of tumoral lymphocyte infiltration TNF-α and IFN-y expression in peripheral T lymphocytes. Results: The in situ immunogel injection after RFA resulted in prolonged survival of mice. Regression of distant lesions was related to the induction of a strong systemic antitumor immune response and a great improvement of tumor infiltration by CD3+ T lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without another treatment. Immune escape of large secondary lesions was reversed by association of the RFA-immunogel vaccination with a systemic immune checkpoint inhibition, separately ineffective. Conclusions: Validation of this strategy, combining RFA of macroscopic lesions and activation of a strong immune response controlling the residual disease, could result in the design of a clinical assay including this approach within a standard treatment of colorectal liver metastases. The synergy between in situ immunomodulation as priming process and checkpoint blockade, ineffective alone in metastatic microsatellite stable CRC or after single RFA, allows reconsidering the use of checkpoint inhibitors in CRC.

scholarly journals Radiation as an In Situ Auto-Vaccination: Current Perspectives and Challenges

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 100 ◽  
Author(s):  
Goto
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
Local Treatment ◽  
Combination Therapies ◽  
Antitumor Effects ◽  
Radiation Induced ◽  
Antigen Presenting

Radiotherapy is generally considered to be a local treatment, but there have been reports of rare cases demonstrating abscopal effects in which antitumor effects have been observed in cancer lesions other than the irradiated site. This result is more likely to occur when immune checkpoint inhibitors are used in addition to radiotherapy. Certain radiation-induced chemokines and cytokines have immune-enhancing effects. Immune checkpoint inhibitors may strengthen these effects by stimulating antigen-presenting cells and effector cytotoxic T cells. To date, there is no consensus regarding the applicability of the abscopal effect in the clinical setting, including optimal methods for combining immune checkpoint inhibitors and irradiation. In this review, we highlight the evidence for interactions between cancer immunotherapy and radiotherapy and discuss the potential of such interactions for use in designing novel combination therapies.

The anti-tumour immune response after radiofrequency ablation of colorectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14540-e14540
Author(s):  
Katia Lemdani ◽  
Claude Capron ◽  
Johanne Seguin ◽  
Nathalie Mignet ◽  
Vincent Boudy ◽  
...  
Keyword(s):  
Immune Response ◽  
Radiofrequency Ablation ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Immune Escape ◽  
Liver Tumors ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Strong Immune Response

e14540 Background: Results of radiofrequency ablation (RFA), increasingly used to treat liver tumors, are compromised by local and systemic relapse. Hyperthermia related cancer cells death, release of tumor antigens and expression of danger signals activate a tumor-specific T-cells response. This effect remains ineffective to avoid recurrence. Therefore we propose to combine RFA with an activation of a solid immune antitumor response as curative treatment of a colorectal (CRC) metastatic disease in immunocompetent mouse. Methods: RFA was used to treat a CT26- luc tumor. In two distinct clinical situations, distant macroscopic or microscopic tumors were established as metastases before or at the time of RFA. Immune response was modulated by an injection in situof a thermo-reversible hydrogel loaded by GM-CSF and BCG, targeting dendritic cells. In the group of mice with large far lesions this strategy was combined with immune checkpoint inhibition. The efficiency was assessed on survival, evolution of distant lesions, characterization of lymphocyte infiltration in tumors and systemic immunity through specific TNF- α and IFN-y expression in spleen and draining lymph nodes. Results: The in situ immunogel injection after RFA resulted in a prolonged survival of mice. Regression of distant lesions was related to a strong systemic antitumor immune response and a great improvement of tumor infiltration by specific cytotoxic lymphocytes. In adjuvant situation, the use of immunogel induced a complete cure of microscopic secondary lesions without any treatment. Immune escape of large secondary lesions was reversed by association of RFA-immunogel vaccination with a systemic check point blockade, separately ineffective. Conclusions: Validation of this strategy, combining RFA of liver metastases and activation of a strong immune response controlling the residual disease, could result in a clinical assay including this approach within the standard treatment of CRC. Furthermorethe powerful synergy between RFA-in situ immunomodulation as a starter treatment and checkpoint blockade ineffective alone in CRC or after single RFA, allows reconsidering the use of immune checkpoint inhibitors in metastatic microsatellite stable CRC.

scholarly journals A Review on LDH-Smart Functionalization of Anodic Films of Mg Alloys

Nanomaterials ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 536
Author(s):  
Mosab Kaseem ◽  
Karna Ramachandraiah ◽  
Shakhawat Hossain ◽  
Burak Dikici
Keyword(s):  
Industrial Applications ◽  
Mg Alloys ◽  
Anodic Films ◽  
Electrolytic Oxidation ◽  
Recent Developments ◽  
Plasma Electrolytic ◽  
Co Precipitation ◽  
Corrosive Environments ◽  
Double Hydroxide

This review presents an overview of the recent developments in the synthesis of layered double hydroxide (LDH) on the anodized films of Mg alloys prepared by either conventional anodizing or plasma electrolytic oxidation (PEO) and the applications of the formed composite ceramics as smart chloride traps in corrosive environments. In this work, the main fabrication approaches including co-precipitation, in situ hydrothermal, and an anion exchange reaction are outlined. The unique structure of LDH nanocontainers enables them to intercalate several corrosion inhibitors and release them when required under the action of corrosion-relevant triggers. The influences of different variables, such as type of cations, the concentration of salts, pH, and temperature, immersion time during the formation of LDH/anodic film composites, on the electrochemical response are also highlighted. The correlation between the dissolution rate of PEO coating and the growth rate of the LDH film was discussed. The challenges and future development strategies of LDH/anodic films are also highlighted in terms of industrial applications of these materials.

scholarly journals IMMU-04. IMMUNE-RELATED ADVERSE EVENTS STRONGLY PREDICT SUPERIOR OUTCOMES IN BRAIN METASTASES PATIENTS RECEIVING LOCAL TREATMENT AND IMMUNE CHECKPOINT INHIBITORS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii105-ii105
Author(s):  
Alexander Hulsbergen ◽  
Asad Lak ◽  
Yu Tung Lo ◽  
Nayan Lamba ◽  
Steven Nagtegaal ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Adverse Events ◽  
Brain Metastases ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Local Treatment ◽  
Sensitivity Analyses ◽  
Immortal Time Bias ◽  
The Brain

Abstract INTRODUCTION In several cancers treated with immune checkpoint inhibitors (ICIs), a remarkable association between the occurrence of immune-related adverse events (irAEs) and superior oncological outcomes has been reported. This effect has hitherto not been reported in the brain. This study aimed to investigate the relation between irAEs and outcomes in brain metastases (BM) patients treated with both local treatment to the brain (LT; i.e. surgery and/or radiation) and ICIs. METHODS This study is a retrospective cohort analysis of patients treated for non-small cell lung cancer (NSCLC) BMs in a tertiary institution in Boston, MA. Outcomes of interest were overall survival (OS) and intracranial progression-free survival (IC-PFS), measured from the time of LT. Sensitivity analyses were performed to account for immortal time bias (i.e., patients who live longer receive more cycles of ICIs and thus have more opportunity to develop an irAE). RESULTS A total of 184 patients were included; 62 (33.7%) were treated with neurosurgical resection and 122 (66.3%) with upfront brain radiation. irAEs occurred in 62 patients (33.7%). After adjusting for lung-Graded Prognostic Assessment, type of LT, type of ICI, newly diagnosed vs. recurrent BM, BM size and number, targetable mutations, and smoking status, irAEs were strongly associated with better OS (HR 0.33, 95% CI 0.19 – 0.58, p < 0.0001) and IC-PFS (HR 0.41; 95% CI 0.26 – 0.65; p = 0.0001). Landmark analysis including only patients who received more than 3 cycles of ICI (n = 133) demonstrated similar results for OS and IC-PFS, as did sensitivity analysis adjusting for the number of cycles administered (HR range 0.36 – 0.51, all p-values < 0.02). CONCLUSIONS After adjusting for known prognostic factors, irAEs strongly predict superior outcomes after LT in NSCLC BM patients. Sensitivity analysis suggests that this is unlikely due to immortal time bias.

scholarly journals Expanded human NK cells from lung cancer patients sensitize patients’ PDL1−negative tumors to PD1-blockade therapy

2021 ◽  
Vol 9 (1) ◽  
pp. e001933
Author(s):  
Sophie M Poznanski ◽  
Tyrah M Ritchie ◽  
Isabella Y Fan ◽  
Abdullah El-Sayes ◽  
Ana L Portillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Death Receptor ◽  
High Rate ◽  
Advanced Lung Cancer ◽  
Pd1 Blockade

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1−blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients’ tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1− patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.

Anodic synthesis of TiO2 nanotubes by step-up voltages

2021 ◽  
pp. 002199832110237
Author(s):  
V Sivaprakash ◽  
R Narayanan
Keyword(s):  
Corrosion Resistance ◽  
Tio2 Nanotubes ◽  
Biomedical Applications ◽  
Phase Changes ◽  
Electrochemical Anodization ◽  
Corrosion Resistant ◽  
Anodization Process ◽  
Anodic Synthesis ◽  
Input Potential

Fabrication of TiO2 nanotubes (NTs) has extensive application properties due to their high corrosion resistant and compatibility with biomedical applications, the synthesis of TiO2 nanotubes over titanium has drawn interest in various fields. The synthesis of TiO2 NTs using novel in-situ step-up voltage conditions in the electrochemical anodization process is recorded in this work. For manufacturing the NTs at 1 hour of anodization, the input potential of 30, 40 and 50 V was selected. With increasing step-up voltage during the anodization process, an improvement in the NTs was observed, favoring corrosion resistance properties. The surface of NTs enhances the structure of the ribs, raising the potential for feedback over time. XRD was used to analyze phase changes, and HR-SEM analyzed surface topography. Impedance tests found that longer NTs improved the corrosion resistance.

scholarly journals Identification of abnormal tribological regimes using a microphone and semi-supervised machine-learning algorithm

Friction ◽  
2021 ◽  
Author(s):  
Vigneashwara Pandiyan ◽  
Josef Prost ◽  
Georg Vorlaufer ◽  
Markus Varga ◽  
Kilian Wasmer
Keyword(s):  
Machine Learning ◽  
Learning Algorithm ◽  
Industrial Applications ◽  
Supervised Machine Learning ◽  
Normal Operation ◽  
Promising Alternative ◽  
Wear And Tear ◽  
Validation Procedure ◽  
And Performance

AbstractFunctional surfaces in relative contact and motion are prone to wear and tear, resulting in loss of efficiency and performance of the workpieces/machines. Wear occurs in the form of adhesion, abrasion, scuffing, galling, and scoring between contacts. However, the rate of the wear phenomenon depends primarily on the physical properties and the surrounding environment. Monitoring the integrity of surfaces by offline inspections leads to significant wasted machine time. A potential alternate option to offline inspection currently practiced in industries is the analysis of sensors signatures capable of capturing the wear state and correlating it with the wear phenomenon, followed by in situ classification using a state-of-the-art machine learning (ML) algorithm. Though this technique is better than offline inspection, it possesses inherent disadvantages for training the ML models. Ideally, supervised training of ML models requires the datasets considered for the classification to be of equal weightage to avoid biasing. The collection of such a dataset is very cumbersome and expensive in practice, as in real industrial applications, the malfunction period is minimal compared to normal operation. Furthermore, classification models would not classify new wear phenomena from the normal regime if they are unfamiliar. As a promising alternative, in this work, we propose a methodology able to differentiate the abnormal regimes, i.e., wear phenomenon regimes, from the normal regime. This is carried out by familiarizing the ML algorithms only with the distribution of the acoustic emission (AE) signals captured using a microphone related to the normal regime. As a result, the ML algorithms would be able to detect whether some overlaps exist with the learnt distributions when a new, unseen signal arrives. To achieve this goal, a generative convolutional neural network (CNN) architecture based on variational auto encoder (VAE) is built and trained. During the validation procedure of the proposed CNN architectures, we were capable of identifying acoustics signals corresponding to the normal and abnormal wear regime with an accuracy of 97% and 80%. Hence, our approach shows very promising results for in situ and real-time condition monitoring or even wear prediction in tribological applications.

Identification of Bearing Coefficients of Flexible Rotor-Bearing Systems

2000 ◽  
Author(s):  
Tachung Yang ◽  
Wei-Ching Chaung
Keyword(s):  
Industrial Applications ◽  
Operating Conditions ◽  
Least Square ◽  
Flexible Rotor ◽  
Fem Modeling ◽  
Identification Method ◽  
Reaction Forces ◽  
Manufacturing Assembly ◽  
Stiffness And Damping

The accuracy of stiffness and damping coefficients of bearings is critical for the rotordynamic analysis of rotating machinery. However, the influence of bearings depends on the design, manufacturing, assembly, and operating conditions of the bearings. Uncertainties occur quite often in manufacturing and assembly, which causes the inaccuracy of bearing predictions. An accurate and reliable in-situ identification method for the bearing coefficients is valuable to both analyses and industrial applications. The identification method developed in this research used the receptance matrices of flexible shafts from FEM modeling and the unbalance forces of trial masses to derive the displacements and reaction forces at bearing locations. Eight bearing coefficients are identified through a Total Least Square (TLS) procedure, which can handle noise effectively. A special feature of this method is that it can identify bearing coefficients at a specific operating speed, which make it suitable for the measurement of speed-dependent bearings, like hydrodynamic bearings. Numerical validation of this method is presented. The configurations of unbalance mass arrangements are discussed.

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