The Impact of Synchrotron Microbeam Radiation Therapy Combined With Broad Beam in a Preclinical Breast Cancer Model.

Purpose: Both local tumor control and distant metastasis are important indicators of the efficacy of radiation therapy treatment. Synchrotron microbeam radiation therapy (MRT), spatially fractionated radiation delivered at ultrahigh dose rates, shows remarkable normal tissue sparing with excellent local control in some models. Some MRT regimens trigger an antitumor immune response that contributes not only to the local but also to systemic treatment efficacy.

Towards melanoma in situ vaccination with multiple ultra-narrow X-ray beams.

Despite the recent progress, current treatment modalities are not able to eradicate cancer. We show that Microbeam Radiotherapy (MRT), an innovative type of Spatially Fractionated Radiotherapy, can control murine melanoma by activating the host's own immune system. The beneficial effects are very pronounced in comparison to uniform radiotherapy traditionally employed in the clinic.

Minibeam Radiation Therapy Treatment (MBRT): Commissioning and First Clinical Implementation.

Purpose: Minibeam radiation therapy (MBRT) is characterized by the delivery of submillimeter-wide regions of high "peak" and low "valley" doses throughout a tumor. Preclinical studies have long shown the promise of this technique, and we report here the first clinical implementation of MBRT.

Methods And Materials: A clinical orthovoltage unit was commissioned for MBRT patient treatments using 3-, 4-, 5-, 8-, and 10-cm diameter cones.

Vascular mimicry in zebrafish fin regeneration: how macrophages build new blood vessels.

Vascular mimicry has been thoroughly investigated in tumor angiogenesis. In this study, we demonstrate for the first time that a process closely resembling tumor vascular mimicry is present during physiological blood vessel formation in tissue regeneration using the zebrafish fin regeneration assay. At the fin-regenerating front, vasculature is formed by mosaic blood vessels with endothelial-like cells possessing the morphological phenotype of a macrophage and co-expressing both endothelial and macrophage markers within single cells.

Combining FLASH and spatially fractionated radiation therapy: The best of both worlds.

FLASH radiotherapy (FLASH-RT) and spatially fractionated radiation therapy (SFRT) are two new therapeutical strategies that use non-standard dose delivery methods to reduce normal tissue toxicity and increase the therapeutic index. Although likely based on different mechanisms, both FLASH-RT and SFRT have shown to elicit radiobiological effects that significantly differ from those induced by conventional radiotherapy. With the therapeutic potential having been established separately for each technique, the combination of FLASH-RT and SFRT could therefore represent a winning alliance.

Microbeam Radiation Therapy Controls Local Growth of Radioresistant Melanoma and Treats Out-of-Field Locoregional Metastasis.

Purpose: Synchrotron-generated microbeam radiation therapy (MRT) represents an innovative preclinical type of cancer radiation therapy with an excellent therapeutic ratio. Beyond local control, metastatic spread is another important endpoint to assess the effectiveness of radiation therapy treatment. Currently, no data exist on an association between MRT and metastasis.

Targeted Accumulation of Macrophages Induced by Microbeam Irradiation in a Tissue-Dependent Manner.

Radiation therapy (RT) is a vital component of multimodal cancer treatment, and its immunomodulatory effects are a major focus of current therapeutic strategies. Macrophages are some of the first cells recruited to sites of radiation-induced injury where they can aid in tissue repair, propagate radiation-induced fibrogenesis and influence tumour dynamics. Microbeam radiation therapy (MRT) is a unique, spatially fractionated radiation modality that has demonstrated exceptional tumour control and reduction in normal tissue toxicity, including fibrosis.

Microbeam Radiotherapy-A Novel Therapeutic Approach to Overcome Radioresistance and Enhance Anti-Tumour Response in Melanoma.

Melanoma is the deadliest type of skin cancer, due to its invasiveness and limited treatment efficacy. The main therapy for primary melanoma and solitary organ metastases is wide excision. Adjuvant therapy, such as chemotherapy and targeted therapies are mainly used for disseminated disease.

Transient and Efficient Vascular Permeability Window for Adjuvant Drug Delivery Triggered by Microbeam Radiation.

Background: Microbeam Radiation Therapy (MRT) induces a transient vascular permeability window, which offers a novel drug-delivery system for the preferential accumulation of therapeutic compounds in tumors. MRT is a preclinical cancer treatment modality that spatially fractionates synchrotron X-rays into micrometer-wide planar microbeams which can induce transient vascular permeability, especially in the immature tumor vessels, without compromising vascular perfusion. Here, we characterized this phenomenon using Chicken Chorioallantoic Membrane (CAM) and demonstrated its therapeutic potential in human glioblastoma xenografts in mice.

Erratum: Fernandez-Palomo, C., et al. Animal Models in Microbeam Radiation Therapy: A Scoping Review. 2020, , 527.

The authors wish to make the following corrections to this paper [...

Bone cancer-induced pain is associated with glutamate signalling in peripheral sensory neurons.

We previously identified that several cancer cell lines known to induce nociception in mouse models release glutamate in vitro. Although the mechanisms of glutamatergic signalling have been characterized primarily in the central nervous system, its importance in the peripheral nervous system has been recognized in various pathologies, including cancer pain. We therefore investigated the effect of glutamate on intracellular electrophysiological characteristics of peripheral sensory neurons in an immunocompetent rat model of cancer-induced pain based on surgical implantation of mammary rat metastasis tumour-1 cells into the distal epiphysis of the right femur.

Animal Models in Microbeam Radiation Therapy: A Scoping Review.

Background: Microbeam Radiation Therapy (MRT) is an innovative approach in radiation oncology where a collimator subdivides the homogeneous radiation field into an array of co-planar, high-dose beams which are tens of micrometres wide and separated by a few hundred micrometres.

Objective: This scoping review was conducted to map the available evidence and provide a comprehensive overview of the similarities, differences, and outcomes of all experiments that have employed animal models in MRT.

Methods: We considered articles that employed animal models for the purpose of studying the effects of MRT.

Applying Serum Cytokine Levels to Predict Pain Severity in Cancer Patients.

Background And Aim: Cancers originating in the breast, lung and prostate often metastasize to the bone, frequently resulting in cancer-induced bone pain that can be challenging to manage despite conventional analgesic therapy. This exploratory study's aim was to identify potential biomarkers associated with cancer-induced pain by examining a sample population of breast cancer patients undergoing bisphosphonate therapy.

Methods: A secondary analysis of the primary study was performed to quantify serum cytokine levels for correlation to pain scores.

Effect of glutaminase inhibition on cancer-induced bone pain.

Purpose: The complex nature of cancer-induced bone pain (CIBP) has led to investigation into cancer-targeted therapies. This has involved targeting glutamate release from the tumor, secreted as a byproduct of antioxidant responses and metabolic disruption. Cancer cells undergo many metabolic changes that result in increased glutamine metabolism and subsequently the production of glutamate.

Biological Entanglement-Like Effect After Communication of Fish Prior to X-Ray Exposure.

The phenomenon by which irradiated organisms including cells in vitro communicate with unirradiated neighbors is well established in biology as the radiation-induced bystander effect (RIBE). Generally, the purpose of this communication is thought to be protective and adaptive, reflecting a highly conserved evolutionary mechanism enabling rapid adjustment to stressors in the environment. Stressors known to induce the effect were recently shown to include chemicals and even pathological agents.

Homogenous and Microbeam X-Ray Radiation Induces Proteomic Changes in the Brains of Irradiated Rats and in the Brains of Nonirradiated Cage Mate Rats.

To evaluate microbeam radiation therapy (MRT), for brain tumor treatment, the bystander effect in nonirradiated companion animals was investigated. Adult rats were irradiated with 35 or 350 Gy at the European Synchrotron Research Facility using homogenous irradiation (HR) or MRT to the right brain hemisphere. The irradiated rats were housed with nonirradiated rats.

Identification of capsazepine as a novel inhibitor of system x and cancer-induced bone pain.

The cystine/glutamate antiporter has been implicated in a variety of cancers as a major mediator of redox homeostasis. The excess glutamate secreted by this transporter in aggressive cancer cells has been associated with cancer-induced bone pain (CIBP) from distal breast cancer metastases. High-throughput screening of small molecule inhibitors of glutamate release from breast cancer cells identified several potential compounds.

Behavioural Effects of Using Sulfasalazine to Inhibit Glutamate Released by Cancer Cells: A Novel target for Cancer-Induced Depression.

Despite the lack of robust evidence of effectiveness, current treatment options for cancer-induced depression (CID) are limited to those developed for non-cancer related depression. Here, anhedonia-like and coping behaviours were assessed in female BALB/c mice inoculated with 4T1 mammary carcinoma cells. The behavioural effects of orally administered sulfasalazine (SSZ), a system x inhibitor, were compared with fluoxetine (FLX).

Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways.

Background: Chronic pain is a major symptom that develops in cancer patients, most commonly emerging during advanced stages of the disease. The nature of cancer-induced pain is complex, and the efficacy of current therapeutic interventions is restricted by the dose-limiting sideeffects that accompany common centrally targeted analgesics.

Methods: This review focuses on how up-regulated glutamate production and export by the tumour converge at peripheral afferent nerve terminals to transmit nociceptive signals through the transient receptor cation channel, TRPV1, thereby initiating central sensitization in response to peripheral disease-mediated stimuli.

Inhibitors of glutamate release from breast cancer cells; new targets for cancer-induced bone-pain.

Glutamate is an important signaling molecule in a wide variety of tissues. Aberrant glutamatergic signaling disrupts normal tissue homeostasis and induces several disruptive pathological conditions including pain. Breast cancer cells secrete high levels of glutamate and often metastasize to bone.

Transmission of signals from rats receiving high doses of microbeam radiation to cage mates: an inter-mammal bystander effect.

Inter-animal signaling from irradiated to non-irradiated organisms has been demonstrated for whole body irradiated mice and also for fish. The aim of the current study was to look at radiotherapy style limited exposure to part of the body using doses relevant in preclinical therapy. High dose homogenous field irradiation and the use of irradiation in the microbeam radiation therapy mode at the European Synchrotron Radiation Facility (ESRF) at Grenoble was tested by giving high doses to the right brain hemisphere of the rat.

Bystander effects in tumor-free and tumor-bearing rat brains following irradiation by synchrotron X-rays.

Purpose: Synchrotron microbeam radiation therapy (MRT) is a radiosurgery concept in the preclinical stage, developed mainly for brain tumor treatment. Experimental studies suggest that with MRT a better therapeutic index can be obtained than with homogenous field radiotherapy, but the underlying cellular mechanisms need further understanding. The aim of this study was to investigate the dynamics of radiation-induced bystander effects (RIBE) in rats after exposing one brain hemisphere to either MRT or homogenous synchrotron radiation (HSR).

Effect of 5-hydroxytryptamine (serotonin) receptor inhibitors on the radiation-induced bystander effect.

Purpose: To test the importance of serotonin as a signaling molecule involved in the production and response of radiation-induced bystander effects.

Materials And Methods: HPV-G human keratinocyte cultures were spiked with various concentrations of Granisetron or Ketanserin and subject to either 0 Gy or 0.5 Gy X-irradiation to observe the inhibitor's effects on bystander signal production.

Evidence for a physical component to the radiation-induced bystander effect?

Purpose: The nature of the transferrable factor which goes from irradiated objects to bystander objects remains undefined. Most agree that a chemical entity is the likely 'factor' although some authors have produced in vitro evidence for the involvement of a physical component or a very potent volatile capable of traveling through air distances. In this paper we test the hypothesis that the communicated signal may be physical at least in part.