Pancreatic Ductal Adenocarcinoma: Current and Emerging Therapeutic Uses of Focused Ultrasound

Lafond, Maxime; Lambin, Thomas; Drainville, Robert Andrew; Dupré, Aurélien; Pioche, Mathieu; Melodelima, David; Lafon, Cyril

doi:10.3390/cancers14112577

Cited by 10 publications

(9 citation statements)

References 126 publications

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“…FUS can induce biological effects within deep tissue in a minimally or non-invasive manner ( Lafond et al, 2022 ). The specific actions of FUS can be divided into two main effects, the thermal and mechanical effects.…”

Section: Focused Ultrasound Technologymentioning

confidence: 99%

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors

Xia

Xiong

et al. 2023

Front. Pharmacol.

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In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in “cold tumors” with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.

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Section: Focused Ultrasound Technologymentioning

confidence: 99%

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors

Xia

Xiong

et al. 2023

Front. Pharmacol.

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“…Recently, the FOLFIRINOX regimen, which combines the drugs leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin [ 5 ], has been recommended [ 6 , 7 ] for improving pancreatic cancer patients’ survival rate by 11.1 months. Due to the poor survival of pancreatic cancer patients, over the last several decades, significant efforts have been made to combine chemo and/or radiation therapies with localized heating, such as microwave [ 8 ], high-intensity focused ultrasound [ 9 ], photodynamic therapy [ 10 ], and magnetic nanoparticle hyperthermia (MNPH) [ 11 , 12 , 13 ] therapies.…”

Section: Introductionmentioning

confidence: 99%

Design and Assessment of a Novel Biconical Human-Sized Alternating Magnetic Field Coil for MNP Hyperthermia Treatment of Deep-Seated Cancer

Shoshiashvili

Shamatava

Kakulia

et al. 2023

Cancers

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Magnetic nanoparticle (MNP) hyperthermia therapy is a treatment technique that can be used alone or as an adjunct to radiation and/or chemotherapies for killing cancer cells. During treatment, MNPs absorb a part of electromagnetic field (EMF) energy and generate localized heat when subjected to an alternating magnetic field (AMF). The MNP-absorbed EMF energy, which is characterized by a specific absorption rate (SAR), is directly proportional to AMF frequency and the magnitude of transmitting currents in the coil. Furthermore, the AMF penetrates inside tissue and induces eddy currents in electrically conducting tissues, which are proportional to the electric field (J = σE). The eddy currents produce Joule heating (<J·E> = 0.5·σ·E2) in the normal tissue, the rate of energy transfer to the charge carriers from the applied electric fields. This Joule heating contains only the electric field because the magnetic field is always perpendicular to the velocity of the conduction charges, i.e., it does not produce work on moving charge. Like the SAR due to MNP, the electric field produced by the AMF coil is directly proportional to AMF frequency and the magnitude of transmitting currents in the coil. As a result, the Joule heating is directly proportional to the square of the frequency and transmitter current magnitude. Due to the fast decay of magnetic fields from an AMF coil over distance, MNP hyperthermia treatment of deep-seated tumors requires high-magnitude transmitting currents in the coil for clinically achievable MNP distributions in the tumor. This inevitably produces significant Joule heating in the normal tissue and becomes more complicated for a standard MNP hyperthermia approach for deep-seated tumors, such as pancreatic, prostate, liver, lung, ovarian, kidney, and colorectal cancers. This paper presents a novel human-sized AMF coil and MNP hyperthermia system design for safely and effectively treating deep-seated cancers. The proposed design utilizes the spatial distribution of electric and magnetic fields of circular coils. Namely, it first minimizes the SAR due to eddy currents in the normal tissue by moving the conductors away from the tissue (i.e., increasing coils’ radii), and second, it increases the magnetic field at the targeted area (z = 0) due to elevated coils (|z| > 0) by increasing the radius of the elevated coils (|z| > 0). This approach is a promising alternative aimed at overcoming the limitation of standard MNP hyperthermia for deep-seated cancers by taking advantage of the transmitter coil’s electric and magnetic field distributions in the human body for maximizing AMF in tumor regions and avoiding damage to normal tissue. The human-sized coil’s AMF, MNP activation, and eddy current distribution characteristics are investigated for safe and effective treatment of deep-seated tumors using numerical models. Namely, computational results such as AMF, Joule heating SAR, and temperature distributions are presented for a full-body, 3D human model. The SAR and temperature distributions clearly show that the proposed human-sized AMF coil can provide clinically relevant AMF to the region occupied by deep-seated cancers for the application of MNP hyperthermia therapy while causing less Joule heating in the normal tissues than commonly used AMF techniques.

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“…The early application focused on the thermal effect of high‐intensity focused ultrasound (HIFU), which could focus heat on a focal zone. Based on its characteristics of high intensity and focusing, HIFU was used for tissue ablation or tumor treatment 3–5 . However, the non‐thermal effects of ultrasound (mechanical effects and cavitation effects) have attracted much more attention, so LI‐US has become a research hotspot as a specific non‐invasive technology 6 …”

Section: Introductionmentioning

confidence: 99%

“…Based on its characteristics of high intensity and focusing, HIFU was used for tissue ablation or tumor treatment. [3][4][5] However, the non-thermal effects of ultrasound (mechanical effects and cavitation effects) have attracted much more attention, so LI-US has become a research hotspot as a specific non-invasive technology. 6 LI-US defined as a ultrasonic wave with an effective sound intensity of <3 W/cm 2 , 7 while diagnostic US utilizes 0.001-0.1 W/cm 2 , and therapeutic high-intensity US (like HIFU) uses 100-10,000 W/cm 2 .…”

mentioning

confidence: 99%

A Bibliometric Analysis for Low‐Intensity Ultrasound Study Over the Past Three Decades

Chang

Wang

Liu

et al. 2023

J of Ultrasound Medicine

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Low‐intensity ultrasound (LI‐US) is a non‐invasive stimulation technique that has emerged in recent years and has been shown to have positive effects on neuromodulation, fracture healing, inflammation improvement, and metabolic regulation. This study reports the conclusions of a bibliometric analysis of LI‐US. Input data for the period between 1995 and 2022, including 7209 related articles in the field of LI‐US, were collected from the core library of the Web of Science (WOS) database. Using these data, a set of bibliometric indicators was obtained to gain knowledge on different aspects: global production, research areas, and sources analysis, contributions of countries and institutions, author analysis, citation analysis, and keyword analysis. This study combined the data analysis capabilities provided by the WOS database, making use of two bibliometric software tools: R software and VOS viewer to achieve analysis and data exploration visualization, and predicted the further development trends of LI‐US. It turns out that the United States and China are co‐leaders while Zhang ZG is the most significant author in LI‐US. In the future, the hot spots of LI‐US will continue to focus on parameter research, mechanism discussion, safety regulations, and neuromodulation applications.

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Pancreatic Ductal Adenocarcinoma: Current and Emerging Therapeutic Uses of Focused Ultrasound

Cited by 10 publications

References 126 publications

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors

Focused ultrasound-mediated small-molecule delivery to potentiate immune checkpoint blockade in solid tumors

Design and Assessment of a Novel Biconical Human-Sized Alternating Magnetic Field Coil for MNP Hyperthermia Treatment of Deep-Seated Cancer

A Bibliometric Analysis for Low‐Intensity Ultrasound Study Over the Past Three Decades

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