News & Press Releases

View the latest news from Xstrahl and partners.

Treating the Nasal Ala with Superficial Radiotherapy

Nasal function and cosmesis are important considerations in the quality of life for nasal ala skin cancer patients. Surgery involves tissue loss, which is likely to lead to impaired function and undesired cosmetic results. Superficial radiotherapy can be an effective alternative without these negative side effects, if administered in proper doses. The case studies featured […]

Dermatologist Highlights RADiant Benefits

Sorry, this entry is only available in American English. For the sake of viewer convenience, the content is shown below in the alternative language. You may click the link to switch the active language. Over his career, Dr. Steven Davis, medical director of The Dermatology & Laser Center of San Antonio has performed over 25,000 […]

SARRP Immobilization Devices

Sorry, this entry is only available in American English. For the sake of viewer convenience, the content is shown below in the alternative language. You may click the link to switch the active language. Xstrahl’s new mouse immobilization suite gives you the flexibility you need for your experiments. With over 85% of image guided irradiation […]

Special Presentation from 5th Conference on Small Animal Precision Image-Guided Radiotherapy

Sorry, this entry is only available in American English. For the sake of viewer convenience, the content is shown below in the alternative language. You may click the link to switch the active language. As we navigate this season of social distancing, we are doing what we can to be available to our network. Part […]

New Radiation Research Technology, SARRP Beamline, Advances Preclinical Particle Research to Optimize and Validate Cancer Treatment Protocols

Sorry, this entry is only available in American English. For the sake of viewer convenience, the content is shown below in the alternative language. You may click the link to switch the active language. For a subset of cancers, the exciting world of ion beam, proton beam and FLASH radiotherapy have presented new opportunities to […]

Xstrahl 150 Used as System of Choice for Australian Case Study Reviews

With the rates of skin cancers ever increasing, especially in places with high sun prevalence, treatment of these conditions can cause not only a demand on resources, but there is a lack of unified response and the best way to treat. This is why Prof. Gerald Fogarty of GenesisCare in Australia has used the Xstrahl […]

Xstrahl Partners with C&C Irradiator Service to Supply Safe Irradiation Systems in the U.S.A.

October 3rd, 2019 Xstrahl and Washington DC-based C&C Irradiator Service are announcing a partnership to supply next generation X-ray irradiator systems to replace cesium sources across the U.S. Used throughout the world, with hundreds in the United States, Cesium-137 is a radioactive source used in equipment such as older generation radiotherapy systems and irradiators. However, […]

Early-onset aging and mitochondrial defects associated with loss of histone acetyltransferase 1 (Hat1).

Histone acetyltransferase 1 (Hat1) is responsible for the acetylation of newly synthesized histone H4 on lysines 5 and 12 during the process of chromatin assembly. To understand the broader biological role of Hat1, we have generated a conditional mouse knockout model of this enzyme. We previously reported that Hat1 is required for viability and important […]

Open Call for Animal Models in Radiotherapy Research

September 18th Open call for original research articles and current reviews dedicated to the development and application of animal models in radiotherapy research for publication in Cancers.   Animal models are essential tools in radiotherapy research that have played critical roles in developing our understanding of tumour and normal tissue response. With recent advances in […]

Xstrahl Spotlights Full Range of X-Ray Therapy and Radiation Research Systems at ASTRO 2019

September 13th, 2019 New X-ray radiotherapy image guidance system and SARRP beamline research platform among advanced new solutions showcased on Xstrahl booth (No. 4028) at American Society for Radiation Oncology annual meeting in Chicago, September 15th-18th. Xstrahl, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is spotlighting its full […]

Beam size limit for pencil minibeam radiotherapy determined from side effects in an in-vivo mouse ear model

Side effects caused by radiation are a limiting factor to the amount of dose that can be applied to a tumor volume. A novel method to reduce side effects in radiotherapy is the use of spatial fractionation, in which a pattern of sub-millimeter beams (minibeams) is applied to spare healthy tissue. In order to determine […]

Xstrahl Launches New Modules on its Free Online Learning Platform

August 28th, 2019 Xstrahl, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is launching new dermatology-specific modules to the Xstrahl Learning Portal. This comprehensive free resource, which already contains modules aimed at radiographers, now also provides all current and future dermatology professionals with access to over 20 years of […]

Preclinical dose verification using a 3D printed mouse phantom for radiobiology experiments.

PURPOSE: Dose verification in preclinical radiotherapy is often challenged by a lack of standardization in the techniques and technologies commonly employed along with the inherent difficulty of dosimetry associated with small-field kilovoltage sources. As a consequence, the accuracy of dosimetry in radiobiological research has been called into question. Fortunately, the development and characterization of realistic […]

Xstrahl Launches the New SARRP Beamline for Proton, Photon, Carbon and Flash Pre-Clinical Experiments

August 26th, 2019 The new SARRP beamline pre-clinical radiation research and CT imaging platform launched at the Xstrahl booth at ICRR in Manchester, UK, August 25th-29th Xstrahl Life Science, global leader in the development of advanced X–ray systems for pre-clinical radiation biology research, is launching its latest radiation research platform. The new SARRP beamline system […]

Xstrahl Introduces Monte Carlo Dose Engine for Fast and Precise Calculations

August 26th, 2019 Xstrahl Life Science, global leader in advanced radiation research systems, is introducing a Monte Carlo dose engine to enable comparative research work to be carried out on its Small Animal Radiation Research Platform (SARRP) system. The new capability will be available in the latest release of Xstrahl’s market leading Muriplan planning system, […]

A critical review of translation processes in pre-clinical radiotherapy associated with limitations in the dosimetry of biological conformational irradiators

Radiotherapy is recognized as one of the main modalities for the treatment of cancer in the world, the translation of the results of the pre-clinical research to clinical trials represents an optimization of the resources destined to combat this disease. Improvements of the dosimetric limitations in the development of radiobiology studies as well as the […]

Xstrahl Launches New Clinical Patient Video

31st July, 2019 Xstrahl has just lauched a new video detailing the journery an average orthovoltage radiotherapy patient will experiance with help from the Cheltenham General Hospital.

The Abscopal Effect of Stereotactic Radiotherapy and Immunotherapy: Fool’s Gold or El Dorado?

An ‘abscopal’ effect if often used to refer to distant tumour regression after localised irradiation. Since the first report of the abscopal effect in the 1950s, well-documented cases with radiotherapy alone are very rare. It is widely accepted that the immune response plays an important role in the abscopal effect, although the mechanism is still […]

USA Today: New technology helps treat skin cancer without surgery

The face of skin cancer is changing, as awareness is at an all-time high and medical technology is rapidly advancing. Still, the Skin Cancer Foundation reports that more than 5.4 million cases of nonmelanoma skin cancer are treated each year in the U.S., affecting 3.3 million people. More people are diagnosed with skin cancer each […]

Design and commissioning of an image-guided small animal radiation platform and quality assurance protocol for integrated proton and x-ray radiobiology research.

Small animal x-ray irradiation platforms are expanding the capabilities and future pathways for radiobiology research. Meanwhile, proton radiotherapy is transitioning to a standard treatment modality in the clinician’s precision radiotherapy toolbox, highlighting a gap between state-of-the-art clinical radiotherapy and small animal radiobiology research. Comparative research of the biological differences between proton and x-ray beams could […]

Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies

Although checkpoint immunotherapies have revolutionized the treatment of cancer, not all tumor types have seen substantial benefit. Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy in which very limited responses to immunotherapy have been observed. Extensive immunosuppressive myeloid cell infiltration in PDAC tissues has been postulated as a major mechanism of resistance to immunotherapy. […]

Xstrahl announces launch of patient-focused, German-language website providing information on treatment options for a range of benign conditions

3rd July, 2019 Xstrahl is announcing the launch of a new, free web-based resource focused on the treatment of benign conditions using orthovoltage radiotherapy. The German-language website (www.xstrahl-roentgentherapie.de) contains a wealth of information for patients and clinicians, and includes comprehensive FAQs about benign conditions and treatment options. Used in dozens of hospitals and clinics across […]

Optimized fractionated radiotherapy with anti-PD-L1 and anti-TIGIT: a promising new combination.

PURPOSE/OBJECTIVE: Radiotherapy (RT) induces an immunogenic antitumor response, but also some immunosuppressive barriers. It remains unclear how different fractionation protocols can modulate the immune microenvironment. Clinical studies are ongoing to evaluate immune checkpoint inhibitors (ICI) in association with RT. However, only few trials aim to optimize the RT fractionation to improve efficacy of these associations. […]

Development of an anatomically correct mouse phantom for dosimetry measurement in small animal radiotherapy research.

Significant improvements in radiotherapy are likely to come from biological rather than technical optimization, for example increasing tumour radiosensitivity via combination with targeted therapies. Such paradigms must first be evaluated in preclinical models for efficacy, and recent advances in small animal radiotherapy research platforms allow advanced irradiation protocols, similar to those used clinically, to be […]

Xstrahl Spotlights Full Range of X-Ray Therapy and Radiation Research Systems at DEGRO 2019, June 13-16

13th June, 2019 Xstrahl Spotlights Full Range of X-Ray Therapy and Radiation Research Systems at DEGRO 2019, June 13-16th  Company also announces launch of patient-focused, German-language website providing information on treatment options for a range of benign conditions Xstrahl, global leader in orthovoltage radiotherapy devices to treat benign dermatological conditions, is showcasing its market-leading range […]

Nestin+NG2+ Cells Form a Reserve Stem Cell Population in the Mouse Prostate

In the prostate, stem and progenitor cell regenerative capacities have been ascribed to both basal and luminal epithelial cells. Here, we show that a rare subset of mesenchymal cells in the prostate are epithelial-primed Nestin-expressing cells (EPNECs) that can generate self-renewing prostate organoids with bipotential capacity. Upon transplantation, these EPNECs can form prostate gland tissue […]

Xstrahl Spotlights New RADiant Treatment System at American Society for Mohs Surgery Annual Meeting

May 23rd, 2019 Xstrahl Spotlights New RADiant Treatment System at American Society for Mohs Surgery Annual Meetingth  Xstrahl Medical, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is spotlighting its RADiant treatment system at the American Society of Mohs Surgery annual meeting in Florida, which this year focuses on […]

Breast Cancer Brain Metastasis Response to Radiation After Microbubble Oxygen Delivery in a Murine Model.

OBJECTIVES: Hypoxic cancer cells have been shown to be more resistant to radiation therapy than normoxic cells. Hence, this study investigated whether ultrasound (US)-induced rupture of oxygen-carrying microbubbles (MBs) would enhance the response of breast cancer metastases to radiation. METHODS: Nude mice (n = 15) received stereotactic injections of brain-seeking MDA-MB-231 breast cancer cells into […]

Xstrahl Spotlights New RADiant Treatment System at Texas Dermatology Society Spring Meeting in Houston

May 17th, 2019 Xstrahl Spotlights New RADiant Treatment System at Texas Dermatology Society Spring Meeting in Houstonth  Xstrahl Medical, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is spotlighting its RADiant treatment system at the Texas Dermatology Society spring meeting on May 17th and 18th at the Marriott Marquis […]

A 3D printed modular phantom for quality assurance of image-guided small animal irradiators: Design, imaging experiments, and Monte Carlo simulations.

PURPOSE: The goal of this work was to develop and test a cylindrical tissue-equivalent quality assurance (QA) phantom for micro computed tomography (microCT) image-guided small animal irradiators that overcomes deficiencies of existing phantoms due to its mouse-like dimensions and composition. METHODS: The 8.6-cm-long and 2.4-cm-diameter phantom was three-dimensionally (3D) printed out of Somos NeXt plastic […]

Xstrahl Introduces One-Stop Shop Treatment System for Non-Melanoma Skin Cancer

April 24th, 2019 New 150kV superficial treatment system spotlighted on Xstrahl booth (No. 3420) at ESTRO show in Milan, Italy, April 26th-29th  Xstrahl Medical, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is launching its latest superficial radiotherapy treatment system.  The new Xstrahl 150 system will be the company’s […]

Enhancing the Therapeutic Efficacy of Cancer Treatment With Cannabinoids.

Over the years, many in vitro and in vivo studies have shown the antineoplastic effects of cannabinoids (CBDs), with reports advocating for investigations of combination therapy approaches that could better leverage these effects in clinical translation. This study explores the potential of combination approaches employing CBDs with radiotherapy (RT) or smart biomaterials toward enhancing therapeutic […]

Xstrahl Spotlights Full Range of X-Ray Therapy and Radiation Research Systems at ESTRO 2019

April 24th, 2019 New 150kV superficial treatment system and SARRP research platform among advanced solutions showcased on Xstrahl booth (No. 3420) at European Society for Radiotherapy & Oncology annual meeting in Milan, April 26th-29th  Xstrahl Medical, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is spotlighting its full range […]

Autophagy Regulation of Metabolism Is Required for CD8+ T Cell Anti-tumor Immunity.

Autophagy is a cell survival process essential for the regulation of immune responses to infections. However, the role of T cell autophagy in anti-tumor immunity is less clear. Here, we demonstrate a cell-autonomous role for autophagy in the regulation of CD8+ T-cell-mediated control of tumors. Mice deficient for the essential autophagy genes Atg5, Atg14, or […]

Xstrahl Launches Free Online Learning Platform

April 2nd, 2019 – Xstrahl Learning Portal is the only free online learning and reference tool for future and current radiotherapy professionals, which is open to everyone Xstrahl Medical, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is launching its new Xstrahl Learning Portal. This comprehensive free resource provides […]

Preclinical models of radiation-induced lung damage: challenges and opportunities for small animal radiotherapy.

Despite a major paradigm shift in radiotherapy planning and delivery over the past three decades with continuing refinements, radiation-induced lung damage (RILD) remains a major dose limiting toxicity in patients receiving thoracic irradiations. Our current understanding of the biological processes involved in RILD which includes DNA damage, inflammation, senescence and fibrosis, is based on clinical […]

Mild hyperthermia as a localized radiosensitizer for deep-seated tumors: investigation in an orthotopic prostate cancer model in mice.

OBJECTIVE Non-ablative or mild hyperthermia (HT) has been shown in preclinical (and clinical) studies as a localized radiosensitizer that enhances the tumoricidal effects of radiation. Most preclinical in vivo HT studies use subcutaneous tumor models which do not adequately represent clinical conditions (e.g. proximity of normal/critical organs) or replicate the tumor microenvironment-both of which are […]

Xstrahl Spotlights New RADiant Treatment System at American Academy of Dermatology Annual Meeting in Washington, D.C.

February 28th, 2019 – Xstrahl Medical, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions, is spotlighting its RADiant treatment system at the American Academy of Dermatology (AAD) annual meeting in Washington from March 1st to 5th. The RADiant system is a small and compact unit specifically designed for use […]

Impact of backscatter material thickness on the depth dose of orthovoltage irradiators for radiobiology research.

The orthovoltage x-ray energy frequently used in radiation research is prone to dosimetry errors due to insufficient backscatter conditions. In many radiobiology studies, especially for cell irradiations, precise dose calculation algorithms such as Convolution-Superposition or Monte Carlo are impractical and as such, less accurate hand calculation methods are used for dose estimation. These dose estimation […]

Xstrahl Enters 20th Year of Customer Technical Training

February 20th, 2019 – Xstrahl Medical, global leader in superficial radiotherapy devices and advanced radiation research systems, is celebrating 20 years of delivering technical training courses on its X-ray treatment systems.  The courses are conducted several times a year at the company’s UK manufacturing hub in Birmingham. When the course was initially conceived 20 years […]

RADiant Treatments Commence at Leading Tennessee Dermatology Center

February 6th, 2019 – A leading dermatology center in Tennessee has commenced advanced skin radiotherapy treatments using the new RADiant treatment system from Xstrahl Medical, global leader in superficial radiotherapy devices to treat non-melanoma skin cancer and dermatological conditions. Dr. Ken Takegami, MD., and his team at Adult and Pediatric Dermatology of Tullahoma, recently completed […]

Blockade of fibroblast activation protein in combination with radiation treatment in murine models of pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic stroma with a poor lymphocyte infiltrate, in part driven by cancer-associated fibroblasts (CAFs). CAFs, which express fibroblast activation protein (FAP), contribute to immune escape via exclusion of anti-tumor CD8+ T cells from cancer cells, upregulation of immune checkpoint ligand expression, immunosuppressive cytokine production, and polarization of […]

Integrating Small Animal Irradiators withFunctional Imaging for Advanced Preclinical Radiotherapy Research.

Translational research aims to provide direct support for advancing novel treatment approaches in oncology towards improving patient outcomes. Preclinical studies have a central role in this process and the ability to accurately model biological and physical aspects of the clinical scenario in radiation oncology is critical to translational success. The use of small animal irradiators […]

Xstrahl Named Best Specialty Radiotherapy System Manufacturer in Annual Global Health & Pharma Awards

January 31st, 2019 – Xstrahl Medical, global leader in superficial radiotherapy devices and advanced radiation research systems, has been named the best specialty radiotherapy systems manufacturer in the 2018 Global Health & Pharma Awards. Xstrahl manufactures advanced radiotherapy systems for both clinical and pre-clinical applications at production facilities in the U.K. and U.S. According to […]

Lung Stereotactic Arc Therapy in Mice: Development of Radiation Pneumopathy and Influence of HIF-1α Endothelial Deletion.

OBJECTIVE Stereotactic body radiation therapy offers good lung local tumor control by the administration of a high dose per fraction in small volumes. Stereotactic body radiation therapy preclinical modeling is now possible, and our aim was to develop a model of focal irradiation of the mouse lung and to investigate the impact of conditional hypoxia-inducible […]

A comprehensive geometric quality assurance framework for preclinical microirradiators

OBJECTIVE The mechanical and geometric accuracy of small animal image‐guided radiotherapy (SA‐IGRT) systems is critical and is affected by a number of system‐related factors. Because of the small dimensions involved in preclinical radiotherapy research, such factors can individually and/or cumulatively contribute to significant errors in the small animal radiation research. In this study, we developed […]

Preclinical Evaluation of Dose-Volume Effects and Lung Toxicity Occurring in- and out-of-field

OBJECTIVES: The aim of this study was to define the dose and dose-volume relationship of radiation induced pulmonary toxicities occurring in and out-of-field in mouse models of early inflammatory and late fibrotic response. MATERIALS AND METHODS: Early radiation induced inflammation and fibrosis were investigated in C3H/NeJ and C57BL/6J mice respectively. Animals were irradiated with 20 […]

Technical note: Manufacturing of a realistic mouse phantom for dosimetry of radiobiology experiments.

PURPOSE: The goal of this work was to design a realistic mouse phantom as a useful tool for accurate dosimetry in radiobiology experiments. METHODS: A subcutaneous tumor-bearing mouse was scanned in a microCT scanner, its organs manually segmented and contoured. The resulting geometries were converted into a stereolithographic file format (STL) and sent to a […]

Development of whole brain versus targeted dentate gyrus irradiation model to explain low to moderate doses of exposure effects in mice.

ABSTRACT: Evaluation of the consequences of low to moderate doses of ionizing radiation (IR) remains a societal challenge, especially for children exposed to CT scans. Appropriate experimental models are needed to improve scientific understanding of how exposure of the postnatal brain to IR affects behavioral functions and their related pathophysiological mechanisms, considering brain complex functional […]

Characterization of a Plastic Scintillating Detector for the Small Animal Radiation Research Platform (SARRP).

PURPOSE: To characterize a small plastic scintillator developed for high resolution, real-time dosimetry of therapy and imaging x-ray beams delivered by an image-guided small animal irradiator. MATERIALS AND METHODS: A 1 mm diameter, 1 mm long polystyrene BCF-60 scintillating fiber dosimeter was characterized with 220 kVp therapy and 40, 50, 60, 70, and 80 kVp […]

Mebendazole and radiation in combination increase survival through anticancer mechanisms in an intracranial rodent model of malignant meningioma.

PURPOSE: Meningiomas are a frequent tumor of the central nervous system. Although mostly benign, approximately 5% present as atypical or malignant tumors. Treatments for atypical meningiomas include gross total resection and radiotherapy, but about 33% of patients have recurrent tumors, sometimes as a higher grade. Recently, the brain penetrant anthelmintic drug, mebendazole, has shown promise […]

Xstrahl Medical Partners with EYMSA to Supply Medical Systems in Mexico

November 6th, 2018 – Xstrahl Medical and Electronica Y Medicina, S.A. (EYMSA) are announcing a partnership to supply next generation superficial radiotherapy systems for the treatment of non-melanoma skin cancers. “The ability to supply much needed radiotherapy systems to Mexico, is a great step forward in our company aim to help cure cancers worldwide, and […]

The potential impact of ultrathin filter design on dosimetry and relative biological effectiveness in modern image-guided small animal irradiators

OBJECTIVE: Modern image-guided small animal irradiators like the Xstrahl Small Animal Radiation Research Platform (SARRP) are designed with ultrathin 0.15  mm Cu filters, which compared with more heavily filtrated traditional cabinet-style biological irradiators, produce X-ray spectra weighted toward lower energies, impacting the dosimetric properties and the relative biological effectiveness (RBE). This study quantifies the effect […]

Interleukin-6 signaling blockade exacerbates acute and late injury from focal intestinal irradiation.

PURPOSE: To evaluate the acute changes in leukocyte populations after focal irradiation and to assess the role of Interleukin-6 (IL6) in acute and late radiation injury. METHODS AND MATERIALS: Mice were surgically implanted with a radiopaque marker on the surface of the small intestine. Mice were then imaged with cone beam computed tomography to locate […]

Evaluation of four different small animal radiation plans on tumour and normal tissue dosimetry in a glioblastoma mouse model.

OBJECTIVES: Small animal radiotherapy research platforms such as XStrahl’s SARRP enable more precise irradiation of tumours and normal tissues in preclinical models of cancer. Using an orthotopic G7 glioblastoma (GBM) xenograft model we studied the impact of four different radiotherapy plans on tumour and normal tissue dosimetry. METHODS: Plans were created using four different approaches […]

Preclinical Modeling of Image-Guided Craniospinal Irradiation for Very-High-Risk Medulloblastoma.

BACKGROUND: Craniospinal irradiation (CSI) is a crucial component of treatment for medulloblastoma (MB), a brain tumor clinically stratified into prognostically distinct molecular subgroups. Preclinical models of clinically-relevant CSI offer the potential to study radiation dose and volume effects in these subgroups and identify subgroup-specific combination adjuvant therapies, particularly for very-high-risk MB in which treatments are […]

Xstrahl Expands Leadership Team

October 30th, 2018 – Xstrahl Medical, global leaders in superficial radiotherapy devices and advanced radiation research systems, has appointed Neil Madle as Commercial Director – Radiotherapy. Based at Xstrahl’s UK head office in Surrey, Madle will be responsible for the commercial performance of the company’s radiotherapy business. Xstrahl’s superficial and orthovoltage radiotherapy systems are used […]

Sydney Vital is the first research centre in Australia to acquire an Xstrahl SARRP

Sydney Vital, a translational cancer research centre funded by the Cancer Institute New South Wales (CINSW) and the University of Sydney, is the first centre in Australia to acquire an Xstrahl Small Animal Radiation Research Platform (SARRP). Sydney Vital’s aim is to take research from the laboratory bench and put it into practice, and by […]

ATR kinase inhibitor AZD6738 potentiates CD8+ T cell-dependent antitumor activity following radiation

DNA damaging chemotherapy and radiation therapy are integrated into the treatment paradigm of the majority of cancer patients. Recently, immunotherapy that targets the immunosuppressive interaction between Programmed Death 1 (PD-1) and its ligand PD-L1 has been approved for malignancies including non-small lung cancer (NSCLC), melanoma, and head and neck squamous cell carcinoma (HNSCC). ATR is […]

Orally bioavailable and blood-brain-barrier penetrating ATM inhibitor (AZ32) radiosensitizes intracranial gliomas in mice

Inhibition of ataxia-telangiectasia mutated (ATM) during radiotherapy of glioblastoma multiforme (GBM) may improve tumor control by short-circuiting the response to radiation-induced DNA damage. A major impediment for clinical implementation is that current inhibitors have limited CNS bioavailability, thus, the goal was to identify ATM inhibitors (ATMi) with improved CNS penetration. Drug screens and refinement of […]

Behavioral Effects of Focal Irradiation in a Juvenile Murine Model

Chemotherapy has been successfully used to reduce radiation dose and volume for most pediatric patients. However, because of the failure of chemotherapeutic agents to cross the blood-brain barrier and the lack of response of some brain tumors to these agents, radiation therapy is still used to treat many childhood cancers with CNS involvement. In this […]

Dosimetric verification and commissioning for a small animal image-guided irradiator

In recent years, small animal image-guided irradiators have been widely utilized in preclinical studies involving rodent models. However, the dosimetry commissioning of such equipment involving kilovoltage small-field dosimetry has not received as much interest as the megavoltage small-field dosimetry used clinically. To date, a paucity of measured kilovoltage beam data, especially for field sizes less […]

MRI-based high-precision irradiation in an orthotopic pancreatic tumor mouse model : A treatment planning study

BACKGROUND: Recently, imaging and high-precision irradiation devices for preclinical tumor models have been developed. Image-guided radiation therapy (IGRT) including innovative treatment planning techniques comparable to patient treatment can be achieved in a translational context. The study aims to evaluate magnetic resonance imaging/computed tomography (MRI/CT)-based treatment planning with different treatment techniques for high-precision radiation therapy (RT). […]

The brain-penetrant clinical ATM inhibitor AZD1390 radiosensitizes and improves survival of preclinical brain tumor models

Poor survival rates of patients with tumors arising from or disseminating into the brain are attributed to an inability to excise all tumor tissue (if operable), a lack of blood-brain barrier (BBB) penetration of chemotherapies/targeted agents, and an intrinsic tumor radio-/chemo-resistance. Ataxia-telangiectasia mutated (ATM) protein orchestrates the cellular DNA damage response (DDR) to cytotoxic DNA […]

Xstrahl opens new German office and facility to expand and support footprint in Europe

Xstrahl announced today the opening of a new office and facility in central Germany to help support its current European install base, and work with local governments and facilities to help ensure radiotherapy treatment is available to everyone who needs it. “As Europe’s preferred orthovoltage radiotherapy system provider, a central location in Europe allows us […]

Dosimetric characterization of a single crystal diamond detector in X-ray beams for preclinical research

The aim of this study was to investigate a single crystal diamond detector, the microDiamond detector from PTW (PTW-Freiburg, Freiburg, Germany), concerning the particular requirements in the set-up and energy range used in small animal radiotherapy (RT) research (around 220kV). We tested it to find out the minimal required pre-irradiation dose, the dose linearity, dose […]

Dosimetric and geometric characteristics of a small animal image‐guided irradiator using 3D dosimetry/optical CT scanner

Purpose The precise dosimetric and geometric characteristics of small animal irradiators are essential to achieving reproducible dose delivery, especially in cases where image‐guidance is utilized. Currently, radiochromic film is the established measurement tool used to evaluate beam characteristics for these systems. However, only 2D information can be acquired with film. This study characterized both the […]

MicroCT imaging dose to mouse organs using a validated Monte Carlo model of the small animal radiation research platform (SARRP)

The goal of this work was to establish imaging dose to mouse organs with a validated Monte Carlo (MC) model of the image-guided Small Animal Radiation Research Platform (SARRP) and to investigate the effect of scatter from the internal walls on animal therapy dose determination. A MC model of the SARRP was built in the […]

Raman Spectroscopic Signatures Reveal Distinct Biochemical and Temporal Changes in Irradiated Human Breast Adenocarcinoma Xenografts

Radiation therapy plays a crucial role in the management of breast cancer. However, current standards of care have yet to accommodate patient-specific radiation sensitivity. Raman spectroscopy is promising for applications in radiobiological studies and as a technique for personalized radiation oncology, since it can detect spectral changes in irradiated tissues. In this study, we used […]

SPRO: “The demand for superficial orthovoltage therapy today exceeds the supply” think the experts of the oldest hospital in St. Petersburg

“The demand for orthovoltage therapy today exceeds the supply,” so think the radiologists at the Mariinsky Hospital in St. Petersburg. The X-ray room has been functioning in the Mariinsky Hospital since 1952 and was first equipped with Russian X-ray therapies. In 2014, the morally and technically obsolete devices were replaced by modern Xstrahl-200 and Xstrahl-300 […]

Velocity-Based Adaptive Registration and Fusion for Fractionated Stereotactic Radiosurgery Using the Small Animal Radiation Research Platform

PURPOSE: To implement Velocity-based image fusion and adaptive deformable registration to enable treatment planning for preclinical murine models of fractionated stereotactic radiosurgery (fSRS) using the small animal radiation research platform (SARRP). METHODS AND MATERIALS: C57BL6 mice underwent 3 unique cone beam computed tomography (CBCT) scans: 2 in the prone position and a third supine. A […]

Importance of dosimetry protocol for cell irradiation on a low X-rays facility and consequences for the biological response

PURPOSE: The main objective of radiobiology is to establish links between doses and radiation-induced biological effects. In this context, well-defined dosimetry protocols are crucial to the determination of experimental protocols. This work proposes a new dosimetry protocol for cell irradiation in a SARRP and shows the importance of the modification of some parameters defined in […]

Development and implementation of EPID-based quality assurance tests for the small animal radiation research platform (SARRP)

PURPOSE: Although small animal image-guided radiotherapy (SA-IGRT) systems are used increasingly in preclinical research, tools for performing routine quality assurance (QA) have not been optimized and are not readily available. Robust, efficient, and reliable QA tools are needed to ensure the accuracy and reproducibility of SA-IGRT systems. Several investigators have reported custom-made phantoms and protocols […]

Xstrahl partners with CTRad and ARR to hold a UK SARRP user group workshop

Xstrahl is delighted to announce a UK SARRP user group workshop taking place on Wednesday June 27th following the 2018 ARR meeting at Queen’s University, Belfast. This is a joint event held by Xstrahl, Clinical and Translational Radiotherapy Research Working Group (CTRad) and Association for Radiation Research (ARR) to encourage collaboration across the UK small […]

Risk Capital Partners backs Xstrahl Buyout

Risk Capital Partners, the private equity firm chaired by Luke Johnson, today announces that it has bought a majority stake in Xstrahl, a medical devices business that designs and delivers effective clinical and research solutions to advance radiation oncology. Xstrahl is a leading designer and manufacturer of superficial orthovoltage X-ray systems used in the treatment […]

Validation of GPU-accelerated superposition-convolution dose computations for the Small Animal Radiation Research Platform

PURPOSE: The Small Animal Radiation Research Platform (SARRP) has been developed for conformal microirradiation with on-board cone beam CT (CBCT) guidance. The graphics processing unit (GPU)-accelerated Superposition-Convolution (SC) method for dose computation has been integrated into the treatment planning system (TPS) for SARRP. This paper describes the validation of the SC method for the kilovoltage […]

Behavioral Effects of Focal Irradiation in a Juvenile Murine Model

Chemotherapy has been successfully used to reduce radiation dose and volume for most pediatric patients. However, because of the failure of chemotherapeutic agents to cross the blood-brain barrier and the lack of response of some brain tumors to these agents, radiation therapy is still used to treat many childhood cancers with CNS involvement. In this […]

Hypoxia imaging with 18F-FAZA PET/CT predicts radiotherapy response in esophageal adenocarcinoma xenografts

BACKGROUND: Esophageal cancer is an aggressive disease with poor survival rates. A more patient-tailored approach based on predictive biomarkers could improve outcome. We aimed to predict radiotherapy (RT) response by imaging tumor hypoxia with 18F-FAZA PET/CT in an esophageal adenocarcinoma (EAC) mouse model. Additionally, we investigated the radiosensitizing effect of the hypoxia modifier nimorazole in […]

Priming the Abscopal Effect Using Multifunctional Smart Radiotherapy Biomaterials Loaded with Immunoadjuvants

In this study, we investigate the use of multifunctional smart radiotherapy biomaterials (SRBs) loaded with immunoadjuvants for boosting the abscopal effect of local radiotherapy (RT). SRBs were designed similar to currently used inert RT biomaterials, incorporating a biodegradable polymer with reservoir for loading payloads of the immunoadjuvant anti-CD40 monoclonal antibody. Lung (LLC1) tumors were generated […]

Improved Overall Survival of Mice by Reducing Lung Side Effects After High-Precision Heart Irradiation Using a Small Animal Radiation Research Platform

PURPOSE: The aim was to reduce radiation exposure of the lung in experimental models to increase overall survival of mice to study late radiation-induced heart disease. METHODS AND MATERIALS: A new irradiation plan was established on the Small Animal Radiation Research Platform machine for local heart irradiation of mice with single doses of 8 and […]

BCN057 induces intestinal stem cell repair and mitigates radiation-induced intestinal injury

Background Radiation-induced gastrointestinal syndrome (RIGS) results from the acute loss of intestinal stem cells (ISC), impaired epithelial regeneration, and subsequent loss of the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, sepsis, and mortality. The high radiosensitivity of the intestinal epithelium limits effective radiotherapy against abdominal malignancies and limits the survival of victims of […]

Sana Klinikum Offenbach: New radiotherapy device for X-ray therapy

Since October 2017, the radiation clinic and MVZ radiotherapy at the Sana Klinikum Offenbach have a new orthovolt device for X-ray irradiation. “We are pleased to be able to offer our patients another treatment option with the new device,” explains chief physician Prof. Dr. med. med. Peter Niehoff. The advantage of the new device is […]

The next evolution in radiotherapy systems is here; RADiant by Xstrahl

January 31st, 2018 – Xstrahl, the leader in X-Ray Technology for treatment of Superficial Skin conditions is pleased to offer the new RADiant therapy system to Physician’s in America. Representing the next generation of compact radiotherapy systems, RADiant’s dual modality provides patients with a pain free, non-surgical alternative for the treatment of non-melanoma skin cancers, […]

Combining radiation with hyperthermia: a multiscale model informed by in vitro experiments

Combined radiotherapy and hyperthermia offer great potential for the successful treatment of radio-resistant tumours through thermo-radiosensitization. Tumour response heterogeneity, due to intrinsic, or micro-environmentally induced factors, may greatly influence treatment outcome, but is difficult to account for using traditional treatment planning approaches. Systems oncology simulation, using mathematical models designed to predict tumour growth and treatment […]

Xstrahl launches Concerto 2.0

January 10th, 2018 – Xstrahl today released an upgrade to its Concerto software streamlining the clinical workflow for the entire range of the Xstrahl systems. Concerto 2.0 provides a streamlined workflow, enhanced connectivity options and a treatment verification module. The key workflow enhancements are: Pre-treatment preparation and independent verification sign off, prior to the patient’s […]

Adrian Treverton has been promoted to Group CEO

January 4th, 2018 – The Xstrahl Group officially announced that Adrian Treverton has been promoted to Group CEO. This comes as the previous CEO, Martin Robinson retired in the new year after working for the company nearly 20 years. Adrian had more than 10 years of industry leadership experience before coming to Xstrahl, as an […]

Unraveling the cell-type dependent radiosensitizing effects of gold through the development of a multifunctional gold nanoparticle

The radiosensitizing efficacy of gold is well established, however, there remain several significant barriers to the successful clinical translation of nano-sized gold particles (AuNPs). These barriers include: retaining stability in relevant biological sera, demonstrating effectiveness at clinically relevant AuNP concentrations and identifying the biological context where significant benefit is most likely to be achieved. Herein […]

Transfer of Minibeam Radiation Therapy into a cost-effective equipment for radiobiological studies: a proof of concept

Minibeam radiation therapy (MBRT) is an innovative synchrotron radiotherapy technique able to shift the normal tissue complication probability curves to significantly higher doses. However, its exploration was hindered due to the limited and expensive beamtime at synchrotrons. The aim of this work was to develop a cost-effective equipment to perform systematic radiobiological studies in view […]

ESTRO ACROP: Technology for precision small animal radiotherapy research: Optimal use and challenges

Many radiotherapy research centers have recently installed novel research platforms enabling the investigation of the radiation response of tumors and normal tissues in small animal models, possibly in combination with other treatment modalities. Many more research institutes are expected to follow in the coming years. These novel platforms are capable of mimicking human radiotherapy more […]

Small field dosimetry for the small animal radiotherapy research platform (SARRP)

BACKGROUND: Preclinical radiation biology has become increasingly sophisticated due to the implementation of advanced small animal image guided radiation platforms into laboratory investigation. These small animal radiotherapy devices enable state-of-the-art image guided therapy (IGRT) research to be performed by combining high-resolution cone beam computed tomography (CBCT) imaging with an isocentric irradiation system. Such platforms are […]

PD-1 Modulates Radiation-Induced Cardiac Toxicity through Cytotoxic T Lymphocytes

INTRODUCTION: Combined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-programmed death 1 (anti-PD-1) drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase […]

Stereotactic Radiotherapy Increases Functionally Suppressive Regulatory T Cells in the Tumor Microenvironment

Radiotherapy (RT) enhances innate and adaptive antitumor immunity; however, the effects of radiation on suppressive immune cells, such as regulatory T cells (Treg), in the tumor microenvironment (TME) are not fully elucidated. Although previous reports suggest an increased Treg infiltration after radiation, whether these Tregs are functionally suppressive remains undetermined. To test the hypothesis that […]

HospiMedica: Low-Cost System Provides an Alternative to Mohs Surgery

A novel RADiant system provides a pain free, non-surgical alternative for the treatment of non-melanoma skin cancer and superficial keloid lesions. The Xstrahl (Camberley, United Kingdom) RADiant System is a mobile, compact, ergonomic superficial X-ray therapy system–operating in the 10-80kV range–designed for superficial radiotherapy and surface electronic brachytherapy of primary malignant epithelial neoplasms and keloids. […]

Xstrahl offers Superficial Radiotherapy to South America

November 9th, 2017 – Following the supply of an Xstrahl 200 to the Island of Cuba, Xstrahl Medical has reached out to the rest of South America and Spanish speaking countries to solve the ever-present problem of skin cancer. Whilst pale skin is at a higher risk of skin cancer, the incidence rate of melanomas […]

Xstrahl RADiant System gets clearance for the US

October 17th, 2017 – The new Xstrahl RADiant System has been granted FDA 510(k) clearance for sale in the US. The RADiant System is a compact and ergonomic superficial X-Ray therapy system operating in the 10kV to 80kV range intended for superficial radiotherapy and surface electronic brachytherapy treatment of primary malignant epithelial neoplasms of the […]

TLR9 stimulation of B-cells induces transcription of p53 and prevents spontaneous and irradiation-induced cell death independent of DNA damage responses. Implications for Common variable immunodeficiency

In the present study, we address the important issue of whether B-cells protected from irradiation-induced cell death, may survive with elevated levels of DNA damage. If so, such cells would be at higher risk of gaining mutations and undergoing malignant transformation. We show that stimulation of B-cells with the TLR9 ligands CpG-oligodeoxynucleotides (CpG-ODN) prevents spontaneous […]

Radiation therapy gets more targeted and personalized

The ultimate goal of radiation therapy has always been to eradicate tumors locally while preventing damage to the surrounding tissue. New technologies aim to make treatment even more precise, while allowing clinicians to better plan treatment strategies and adapt to anatomic changes. Shrinking systems Radiotherapy systems for certain cancers are also getting smaller. Xstrahl recently […]

Radiosensitisation in vivo by histone deacetylase inhibition with no increase in early normal tissue radiation toxicity

As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitising agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity […]

BioXmark for high-precision radiotherapy in an orthotopic pancreatic tumor mouse model : Experiences with a liquid fiducial marker

BACKGROUND AND PURPOSE: High-precision radiotherapy (RT) requires precise positioning, particularly with high single doses. Fiducial markers in combination with onboard imaging are excellent tools to support this. The purpose of this study is to establish a pancreatic cancer mouse model for high-precision image-guided RT (IGRT) using the liquid fiducial marker BioXmark (Nanovi, Kongens Lyngby, Denmark). […]

In Astrakhan appeared a new apparatus for the treatment of skin cancer

The governor of the Astrakhan region Alexander Zhilkin visited the oncology dispensary, where the newest equipment appeared, which allows treating a disease widespread in the hot Astrakhan climate – skin cancer. Skin cancer ranks first among all malignant neoplasms in the Astrakhan region – about 500 people with this disease are treated each year in the oncology dispensary. This […]

BioXmark for high-precision radiotherapy in an orthotopic pancreatic tumor mouse model : Experiences with a liquid fiducial marker.

BACKGROUND AND PURPOSE: High-precision radiotherapy (RT) requires precise positioning, particularly with high single doses. Fiducial markers in combination with onboard imaging are excellent tools to support this. The purpose of this study is to establish a pancreatic cancer mouse model for high-precision image-guided RT (IGRT) using the liquid fiducial marker BioXmark (Nanovi, Kongens Lyngby, Denmark). […]

Evaluation of the radiosensitizing potency of chemotherapeutic agents in prostate cancer cells

PURPOSE: Despite recent advances in the treatment of metastatic prostate cancer, survival rates are low and treatment options are limited to chemotherapy and hormonal therapy. Although ionizing radiation is used to treat localized and metastatic prostate cancer, the most efficient use of radiotherapy is yet to be defined. Our purpose was to determine in vitro […]

Cell-line dependent effects of hypoxia prior to irradiation in squamous cell carcinoma lines

Purpose To assess the impact of hypoxia exposure on cellular radiation sensitivity and survival of tumor cells with diverse intrinsic radiation sensitivity under normoxic conditions. Materials and methods Three squamous cell carcinoma (SCC) cell lines, with pronounced differences in radiation sensitivity, were exposed to hypoxia prior, during or post irradiation. Cells were seeded in parallel […]

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms […]

Inhibition of ataxia telangiectasia related-3 (ATR) improves therapeutic index in preclinical models of non-small cell lung cancer (NSCLC) radiotherapy

BACKGROUND AND PURPOSE: To evaluate the impact of ATR inhibition using AZD6738 in combination with radiotherapy on the response of non-small cell lung cancer (NSCLC) tumour models and a murine model of radiation induced fibrosis. MATERIALS AND METHODS: AZD6738 was evaluated as a monotherapy and in combination with radiation in vitro and in vivo using […]

The Development of Technology for Effective Respiratory-Gated Irradiation Using an Image-Guided Small Animal Irradiator

The development of image-guided small animal irradiators represents a significant improvement over standard irradiators by enabling preclinical studies to mimic radiotherapy in humans. The ability to deliver tightly collimated targeted beams, in conjunction with gantry or animal couch rotation, has the potential to maximize tumor dose while sparing normal tissues. However, the current commercial platforms […]

Role of Na+/Ca2+ Exchangers in Therapy Resistance of Medulloblastoma Cells

BACKGROUND/AIMS: Alterations of cytosolic Ca2+-activity ([Ca2+]i) are decisive in the regulation of tumor cell proliferation, migration and survival. Transport processes participating in the regulation of [Ca2+]i include Ca2+ extrusion through K+-independent (NCX) and/or K+-dependent (NCKX) Na+/Ca2+-exchangers. The present study thus explored whether medulloblastoma cells express Na+/Ca2+-exchangers, whether expression differs between therapy sensitive D283 and therapy […]

Airway Epithelial Cells Are Crucial Targets of Glucocorticoids in a Mouse Model of Allergic Asthma

Although glucocorticoids (GCs) are a mainstay in the clinical management of asthma, the target cells that mediate their therapeutic effects are unknown. Contrary to our expectation, we found that GC receptor (GR) expression in immune cells was dispensable for successful therapy of allergic airway inflammation (AAI) with dexamethasone. Instead, GC treatment was compromised in mice […]

Inhibition of ataxia telangiectasia related-3 (ATR) improves therapeutic index in preclinical models of non-small cell lung cancer (NSCLC) radiotherapy

BACKGROUND AND PURPOSE: To evaluate the impact of ATR inhibition using AZD6738 in combination with radiotherapy on the response of non-small cell lung cancer (NSCLC) tumour models and a murine model of radiation induced fibrosis. MATERIALS AND METHODS: AZD6738 was evaluated as a monotherapy and in combination with radiation in vitro and in vivo using […]

Xstrahl sponsor Educating Doctors at the Skin Cancer Radiotherapy Study Day

July 3rd, 2017 – It has become a good tradition for Xstrahl Medical to sponsor the Skin Cancer Radiotherapy Study Day at Norfolk and Norwich University Hospital, which this year is taking place on 5 August. The one day skin cancer radiotherapy course is for clinical oncology and dermatology trainees and practitioners, especially those specialising […]

Multi-institutional MicroCT image comparison of image-guided small animal irradiators

To recommend imaging protocols and establish tolerance levels for microCT image quality assurance (QA) performed on conformal image-guided small animal irradiators. A fully automated QA software SAPA (small animal phantom analyzer) for image analysis of the commercial Shelley micro-CT MCTP 610 phantom was developed, in which quantitative analyses of CT number linearity, signal-to-noise ratio (SNR), […]

German Patient magazine: Low energy X-ray therapy for pain treatment

The pain relief effect of the radiation was known after the discovery of the x-ray beams at the end of the 19th century. At the beginning of the 20th century the radiation therapy was used to treat not only benign conditions but also malignant tumours. This has changed and the number of benign degenerative and […]

Geislinger Zeitung: Radiation therapy comes to Geislingen

Since mid-May, Geislingen clinic has had a radiotherapy system, which allows the patients to save the time they used to spend to get to the one-minute therapy sessions in Göppingen clinic. The Doctor Dr. Hans-Joachim Thiel is pleased: Since mid-May, the modern radiation therapy system with the futuristic name “Xstrahl 200” has been located in […]

A Two-Phase Expansion Protocol Combining Interleukin (IL)-15 and IL-21 Improves Natural Killer Cell Proliferation and Cytotoxicity against Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in children. Despite intensive research in recent decades the prognosis for patients with metastatic or relapsed diseases has hardly improved. New therapeutic concepts in anti-tumor therapy aim to modulate the patient’s immune system to increase its aggressiveness or targeted effects toward tumor cells. Besides surgery, radiotherapy […]

Cavernous Nerve Injury by Radiation Therapy May Potentiate Erectile Dysfunction in Rats

PURPOSE/OBJECTIVES: Radiation-induced erectile-dysfunction (RiED) is one of the most common side effects of radiation therapy (RT) and significantly reduces the quality of life (QoL) of cancer patients. Approximately 50% of prostate cancer patients experience RiED within 3 to 5 years after completion of RT. A series of vascular, muscular, and neurogenic injuries after prostate RT […]

DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity

Radiotherapy is under investigation for its ability to enhance responses to immunotherapy. However, the mechanisms by which radiation induces anti-tumour T cells remain unclear. We show that the DNA exonuclease Trex1 is induced by radiation doses above 12-18 Gy in different cancer cells, and attenuates their immunogenicity by degrading DNA that accumulates in the cytosol […]

Xstrahl and ORL give sizable donation to the Action Radiotherapy Charity

June 7th, 2017 – Recent surveys show that over half of the British population are unaware that radiotherapy options exist for cancers, benign conditions or palliative care1. This means that thousands of patients could be missing out on the best possible treatment. Action Radiotherapy is campaigning to improve patient access to advanced radiotherapy across the […]

Quality assessment of stereotactic radiosurgery of a melanoma brain metastases model using a mouse-like phantom and the small animal radiation research platform

Purpose/Objective To establish a novel preclinical model for stereotactic radiosurgery with combined mouse-like phantom quality assurance in the setting of brain metastases. Material Methods C57B6 mice underwent intracranial injection of B16-F10 melanoma cells. T1-post contrast MRI was performed on Day 11 after injection. The MRI images were fused with cone beam computed tomography (CBCT) images […]

Identification of protein targets in cerebral endothelial cells for brain arteriovenous malformation (AVMs) molecular therapies

BACKGROUND: To develop a new molecular targeted treatment for brain (AVMs), identification of membrane proteins that are localised on the AVM endothelium is crucial. Current treatment methods are surgery and radiosurgery. However, complete occlusion post radiosurgery are achieved within 3 years, while patient remain at risk of haemorrhage. This study aims to identify potential protein […]

The MTH1 inhibitor TH588 demonstrates anti-tumoral effects alone and in combination with everolimus, 5-FU and gamma-irradiation in neuroendocrine tumor cells

Modulation of the redox system in cancer cells has been considered a promising target for anti-cancer therapy. The novel MTH1 inhibitor TH588 proved tremendous potential in terms of cancer cell eradication, yet its specificity has been questioned by recent reports, indicating that TH588 may also induce cancer cell death by alternative mechanisms than MTH1 inhibition. […]

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

Introduction Preclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse. Methods A multimodality cradle was developed for providing subject immobilisation and its […]

Xstrahl supplies Superficial Radiotherapy to the island of Cuba

April 5th, 2017 – Xstrahl is pleased to announce the supply of the first superficial radiotherapy system – Xstrahl 200 to Havana, Cuba. The equipment was installed in early 2016 and has now been successfully treating Cuban cancer patients for the last 12 months. Xstrahl and Medicuba, the Cuban medical equipment import company, are confident […]

The influence of reference radiation photon energy on high-LET RBE: comparison of human peripheral lymphocytes and human-hamster hybrid AL cells.

The relative biological effectiveness (RBE) based on the induction of dicentrics in any cell type is principally an important information for the increasing application of high-LET radiation in cancer therapy. Since the standard system of human lymphocytes for measuring dicentrics are not compatible with our microbeam irradiation setup where attaching cells are essential, we used […]

Activating Akt1 mutations alter DNA double strand break repair and radiosensitivity

The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with […]

Structure-guided development of a high-af fi nity human Programmed Cell Death-1: Implications for tumor immunotherapy

Programmed Cell Death-1 (PD-1) is an inhibitory immune receptor, which plays critical roles in T cell co-inhibi-tion and exhaustion upon binding to its ligands PD-L1 and PD-L2. We report the crystal structure of the human PD-1 ectodomain and the mapping of the PD-1 binding interface. Mutagenesis studies confirmed the crystallo-graphic interface, and resulted in mutant […]

The Need for Accurate Dosimetry in Pre-Clinical Radiobiology Studies

Dose measurements in pre-clinical and radiobiology studies are frequently inadequate, thus undermining the reliability and reproducibility of the published findings.
Anna Subiel, Giuseppe Schettino et al
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Activating Akt1 mutations alter DNA double strand break repair and radiosensitivity

The survival kinase Akt has clinical relevance to radioresistance. However, its contributions to the DNA damage response, DNA double strand break (DSB) repair and apoptosis remain poorly defined and often contradictory. We used a genetic approach to explore the consequences of genetic alterations of Akt1 for the cellular radiation response. While two activation-associated mutants with […]

The significance of Trk receptors in pancreatic cancer

This study investigated the Trk receptor family as a therapeutic target in pancreatic ductal adenocarcinoma and assessed their prognostic significance. Global gene expression analysis was investigated in prospectively collected pancreatic ductal adenocarcinomas that had either undergone neoadjuvant chemoradiation or were treated by surgery. PANC-1 and MIA-PaCa-2 cell lines were investigated to establish whether fractionated radiation […]

Profiling of a panel of radioresistant prostate cancer cells identifies deregulation of key miRNAs

Background miRNAs are increasingly associated with the aggressive phenotype of prostate tumours. Their ability to control radiobiologically-relevant cellular processes strengthens their potential as novel markers of response to radiation therapy. Purpose To identify miRNAs associated with increased clonogenic survival following radiation exposure. Material and methods The miRNA expression profiles of a panel of 22RV1 cells […]

Intravenous Formulation of HET0016 Decreased Human Glioblastoma Growth and Implicated Survival Benefit in Rat Xenograft Models

Glioblastoma (GBM) is a hypervascular primary brain tumor with poor prognosis. HET0016 is a selective CYP450 inhibitor, which has been shown to inhibit angiogenesis and tumor growth. Therefore, to explore novel treatments, we have generated an improved intravenous (IV) formulation of HET0016 with HPßCD and tested in animal models of human and syngeneic GBM. Administration […]

Development of A Novel Murine Model of Combined Radiation and Peripheral Tissue Trauma Injuries

Detonation of a 10-kiloton nuclear bomb in an urban setting would result in >1 million casualties, the majority of which would present with combined injuries. Combined injuries, such as peripheral tissue trauma and radiation exposure, trigger inflammatory events that lead to multiple organ dysfunction (MOD) and death, with gastrointestinal (GI) and pulmonary involvement playing crucial […]

RAD51 Is a Selective DNA Repair Target to Radiosensitize Glioma Stem Cells

Patients with glioblastoma die from local relapse despite surgery and high-dose radiotherapy. Resistance to radiotherapy is thought to be due to efficient DNA double-strand break (DSB) repair in stem-like cells able to survive DNA damage and repopulate the tumor. We used clinical samples and patient-derived glioblastoma stem cells (GSCs) to confirm that the DSB repair […]

Progression-related loss of stromal Caveolin 1 levels fosters the growth of human PC3 xenografts and mediates radiation resistance

Despite good treatment results in localized prostate tumors, advanced disease stages usually have a pronounced resistance to chemotherapy and radiotherapy. The membrane protein caveolin-1 (Cav1) functions here as an important oncogene. Therefore we examined the impact of stromal Cav1 expression for tumor growth and sensitivity to ionizing radiation (IR). Silencing of Cav1 expression in PC3 […]

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems

Background and Purpose: Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). Materials and Methods: The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. […]

A kernel-based dose calculation algorithm for kV photon beams with explicit handling of energy and material dependencies

OBJECTIVE: Mimicking state-of-the-art patient radiotherapy with high-precision irradiators for small animals is expected to advance the understanding of dose-effect relationships and radiobiology in general. We work on the implementation of intensity-modulated radiotherapy-like irradiation schemes for small animals. As a first step, we present a fast analytical dose calculation algorithm for keV photon beams. METHODS: We […]

A Novel Mouse Model to Study Image-Guided, Radiation-Induced Intestinal Injury and Preclinical Screening of Radioprotectors. Verginadis II1, Kanade R1, Bell B1, Koduri S2, Ben-

Radiation is an important treatment modality for gastrointestinal tumors, but intestinal injury is a common side effect. Here we describe a physiologically relevant model for studying the molecular determinants of radiation-induced intestinal damage and testing novel radioprotectors. The model employs a radiopaque marker implanted into the surface of the mouse jejunum, serving as a fiducial […]

Patient-Specific Screening Using High-Grade Glioma Explants to Determine Potential Radiosensitization by a TGF-β Small Molecule Inhibitor

High-grade glioma (HGG), a deadly primary brain malignancy, manifests radioresistance mediated by cell-intrinsic and microenvironmental mechanisms. High levels of the cytokine transforming growth factor-β (TGF-β) in HGG promote radioresistance by enforcing an effective DNA damage response and supporting glioma stem cell self-renewal. Our analysis of HGG TCGA data and immunohistochemical staining of phosphorylated Smad2, which […]

Commissioning and evaluation of a new commercial small animal radiation research platform Xstrahl XenX irradiator

Introduction The aim of this study was to perform the commissioning and acceptance tests of the commercial small animal radiation research platforms Xsthral XenX irradiator. Methods The Xstrahl-Xenx irradiator contains an X-ray tube with potentials of 20–220 kVp range. The inherent filtration of X-ray tube is 0.8 mm (Be). An additional filtration of 0.15 mm (Cu) is used […]

Enhancing radiotherapy for lung cancer using immunoadjuvants delivered in situ from new design radiotherapy biomaterials: a preclinical study

Studies show that radiotherapy of a primary tumor in combination with immunoadjuvants (IA) can result in increased survival or immune-mediated regression of metastasis outside the radiation field, a phenomenon known as abscopal effect. However, toxicities due to repeated systematic administration of IA have been shown to be a major obstacle in clinical trials. To minimize […]

Intratumoral G100 Rescues Radiation-Induced T Cell Depletion and Has Synergistic Anti-Tumor Effect with Local Irradiation in A20 Lymphoma

Background: Radiation therapy is a standard established treatment modality for many malignancies, including lymphoma. There is growing evidence that the combination of radiation and immunotherapies can have synergistic immune and clinical effects; however, the mechanisms underlying these responses are poorly understood. Hypothesis: We hypothesized that the potential beneficial effect of adding immunotherapy to radiation might […]

An image-guided precision proton radiation platform for preclinical in vivo research

There are many unknowns in the radiobiology of proton beams and other particle beams. We describe the development and testing of an image-guided low-energy proton system optimized for radiobiological research applications. A 50 MeV proton beam from an existing cyclotron was modified to produce collimated beams (as small as 2 mm in diameter). Ionization chamber and […]

Evaluation of On- and Off-Line Bioluminescence Tomography System for Focal Irradiation Guidance

In response to the limitations of computed tomography (CT) and cone-beam CT (CBCT) in irradiation guidance, especially for soft-tissue targets without the use of contrast agents, our group developed a solution that implemented bioluminescence tomography (BLT) as the image-guidance modality for preclinical radiation research. However, adding such a system to existing small animal irradiators is […]

Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma

The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) […]

Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

PURPOSE: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. METHODS AND […]

Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy

Radiation therapy provides a means to kill large numbers of cancer cells in a controlled location resulting in the release of tumor-specific antigens and endogenous adjuvants. However, by activating pathways involved in apoptotic cell recognition and phagocytosis, irradiated cancer cells engender suppressive phenotypes in macrophages. We demonstrate that the macrophage-specific phagocytic receptor, Mertk is upregulated […]

A mouse model replicating hippocampal sparing cranial irradiation in humans: A tool for identifying new strategies to limit neurocognitive decline

Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG 0933 […]

Fractionated radiation exposure amplifies the radioresistant nature of prostate cancer cells

The risk of recurrence following radiation therapy remains high for a significant number of prostate cancer patients. The development of in vitro isogenic models of radioresistance through exposure to fractionated radiation is an increasingly used approach to investigate the mechanisms of radioresistance in cancer cells and help guide improvements in radiotherapy standards. We treated 22Rv1 […]

MRI-guided radiotherapy of the SK-N-SH neuroblastoma xenograft model using a small animal radiation research platform

OBJECTIVE: Neuroblastoma has one of the lowest survival rates of all childhood cancers, despite the use of intensive treatment regimens. Preclinical models of neuroblastoma are essential for testing new multimodality protocols, including those that involve radiotherapy (RT). The aim of this study was to develop a robust method for RT planning and tumour response monitoring […]

An evaluation in vitro of PARP-1 inhibitors, rucaparib and olaparib, as radiosensitisers for the treatment of neuroblastoma

Background The radiopharmaceutical 131I-meta-iodobenzylguanidine (131I-MIBG) is an effective treatment for neuroblastoma. However, maximal therapeutic benefit from 131I-MIBG is likely to be obtained by its combination with chemotherapy. We previously reported enhanced antitumour efficacy of 131I-MIBG by inhibition of the poly(ADP-ribose) polymerase-1 (PARP-1) DNA repair pathway using the phenanthridinone derivative PJ34. Recently developed alternative PARP-1 inhibitors […]

Programmed cell death-1 blockade enhances response to stereotactic radiation in an orthotopic murine model of hepatocellular carcinoma

AIM: Small, solitary hepatocellular carcinoma is curable with stereotactic radiation or other methods of tumor ablation, however, regional and systemic tumor recurrence occurs in over 70% of patients. Here we describe the ability of immunoradiotherapy to induce an antitumor immune response and delay the growth of tumors in immunocompetent mice. METHODS: A syngeneic hepatocellular carcinoma […]

Modelling responses to spatially fractionated radiation fields using preclinical image-guided radiotherapy

OBJECTIVE: Radiotherapy is planned to achieve the optimal physical dose distribution to the target tumour volume whilst minimizing dose to the surrounding normal tissue. Recent in vitro experimental evidence has demonstrated an important role for intercellular communication in radiobiological responses following non-uniform exposures. This study aimed to model the impact of these effects in the […]

Kinetic Modeling and Graphical Analysis of 18F-Fluoromethylcholine (FCho), 18F-Fluoroethyltyrosine (FET) and 18F-Fluorodeoxyglucose (FDG) PET for the Fiscrimination between High-Grade Glioma and Radiation Necrosis in Rats

Background Discrimination between glioblastoma (GB) and radiation necrosis (RN) post-irradiation remains challenging but has a large impact on further treatment and prognosis. In this study, the uptake mechanisms of 18F-fluorodeoxyglucose (18F-FDG), 18F-fluoroethyltyrosine (18F-FET) and 18F-fluoromethylcholine (18F-FCho) positron emission tomography (PET) tracers were investigated in a F98 GB and RN rat model applying kinetic modeling (KM) […]

Stereotactic Body Radiation Therapy Delivery in a Genetically Engineered Mouse Model of Lung Cancer

Purpose To implement clinical stereotactic body radiation therapy (SBRT) using a small animal radiation research platform (SARRP) in a genetically engineered mouse model of lung cancer. Methods and Materials A murine model of multinodular Kras-driven spontaneous lung tumors was used for this study. High-resolution cone beam computed tomography (CBCT) imaging was used to identify and […]

Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy

Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The […]

Preclinical evaluation of gold-DTDTPA nanoparticles as theranostic agents in prostate cancer radiotherapy

AIM: Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and radiosensitization in prostate cancer. MATERIALS & METHODS: In vitro assays determined Au@DTDTPA uptake, cytotoxicity, radiosensitizing potential and DNA damage profiles. Human PC3 xenograft tumor […]

FLIP: A Targetable Mediator of Resistance to Radiation in Non-Small Cell Lung Cancer

Resistance to radiotherapy due to insufficient cancer cell death is a significant cause of treatment failure in non-small cell lung cancer (NSCLC). The endogenous caspase-8 inhibitor FLIP is a critical regulator of cell death that is frequently overexpressed in NSCLC and is an established inhibitor of apoptotic cell death induced via the extrinsic death receptor […]

Optimizing Timing of Immunotherapy Improves Control of Tumors by Hypofractionated Radiation Therapy

The anecdotal reports of promising results seen with immunotherapy and radiation in advanced malignancies have prompted several trials combining immunotherapy and radiation. However, the ideal timing of immunotherapy with radiation has not been clarified. Tumor bearing mice were treated with 20Gy radiation delivered only to the tumor combined with either anti-CTLA4 antibody or anti-OX40 agonist […]

Synergy of radiotherapy and PD-1 blockade in Kras-mutant lung cancer

Radiation therapy (RT), a critical modality in the treatment of lung cancer, induces direct tumor cell death and augments tumor-specific immunity. However, despite initial tumor control, most patients suffer from locoregional relapse and/or metastatic disease following RT. The use of immunotherapy in non–small-cell lung cancer (NSCLC) could potentially change this outcome by enhancing the effects […]

Tumor-derived CCL2 mediates resistance to radiotherapy in pancreatic ductal adenocarcinoma

Purpose: Local tumor growth is a major cause of morbidity and mortality in nearly 30% of patients with pancreatic ductal adenocarcinoma (PDAC). Radiotherapy (RT) is commonly used for local disease control in PDAC, but efficacy is limited. We studied the impact of selectively intervening on RT-induced inflammation as an approach to overcome resistance to RT […]

A preclinical murine model for the early detection of radiation-induced brain injury using magnetic resonance imaging and behavioral tests for learning and memory: with applications for the evaluation of possible stem cell imaging agents and therapies.

Stem cell therapies are being developed for radiotherapy-induced brain injuries (RIBI). Magnetic resonance imaging (MRI) offers advantages for imaging transplanted stem cells. However, most MRI cell-tracking techniques employ superparamagnetic iron oxide particles (SPIOs), which are difficult to distinguish from hemorrhage. In current preclinical RIBI models, hemorrhage occurs concurrently with other injury markers. This makes the evaluation of the recruitment of transplanted SPIO-labeled [...]

Radiation Therapy Induces Macrophages to Suppress Immune Responses Against Pancreatic Tumors in Mice.

The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated whether radiation causes inflammatory cells to acquire an immune-suppressive phenotype that limits the [...]

Hypoxia Potentiates the Radiation-Sensitizing Effect of Olaparib in Human Non-Small Cell Lung Cancer Xenografts by Contextual Synthetic Lethality.

We proposed to exploit hypoxia-inducible factor (HIF)-1alpha overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF-1alpha to arrangements of hypoxia response elements. CD is a prodrug activation enzyme, which converts inactive 5-fluorocytosine to active 5-fluorouracil (5-FU), allowing selective killing of vector containing cells.
Laure Marignol, Ruth Foley, Thomas Southgate, [...]

The effect of irradiation on tumor microenvironment and bone marrow cell migration in a pre-clinical tumor model.

To characterize the tumor microenvironment after standard radiation therapy (SRT) and pulsed radiation therapy (PRT) in Lewis lung carcinoma (LLC) allografts.
Jonathan L Kane, Sarah A Krueger, Alaa Hanna, Thomas R Raffel, George D Wilson, Gerard J Madlambayan and Brian Marples
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Potential Effect of Liposomes and Liposome-Encapsulated Botulinum Toxin and Tacrolimus in the Treatment of Bladder Dysfunction.

Bladder drug delivery via catheter instillation is a widely used treatment for recurrence of superficial bladder cancer. Intravesical instillation of liposomal botulinum toxin has recently shown promise in the treatment of overactive bladder and interstitial cystitis/bladder pain syndrome, and studies of liposomal tacrolimus instillations show promise in the treatment of hemorrhagic cystitis. Liposomes are lipid vesicles composed of phospholipid bilayers surrounding an aqueous core that can [...]

NF-kB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor supression.

Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα [...]

Radiation Therapy Induces Macrophages to Suppress T-Cell Responses Against Pancreatic Tumors in Mice

Background & Aims The role of radiation therapy in the treatment of patients with pancreatic ductal adenocarcinoma (PDA) is controversial. Randomized controlled trials investigating the efficacy of radiation therapy in patients with locally advanced unresectable PDA have reported mixed results, with effects ranging from modest benefit to worse outcomes compared with control therapies. We investigated […]

Low-Intensity Focused Ultrasound Induces Reversal of Tumor-Induced T Cell Tolerance and Prevents Immune Escape.

In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based on a newly developed reconstruction algorithm.
Zhang B, Wang KK, Yu J, Eslami S, [...]

MRI-Only Based Radiotherapy Treatment Planning for the Rat Brain on a Small Animal Radiation Research Platform (SARRP)

Computed tomography (CT) is the standard imaging modality in radiation therapy treatment planning (RTP). However, magnetic resonance (MR) imaging provides superior soft tissue contrast, increasing the precision of target volume selection. We present MR-only based RTP for a rat brain on a small animal radiation research platform (SARRP) using probabilistic voxel classification with multiple MR […]

Quantitative correlational study of microbubble-enhanced ultrasound imaging and magnetic resonance imaging of glioma and early response to radiotherapy in a rat model

PURPOSE: Radiotherapy remains a major treatment method for malignant tumors. Magnetic resonance imaging (MRI) is the standard modality for assessing glioma treatment response in the clinic. Compared to MRI, ultrasound imaging is low-cost and portable and can be used during intraoperative procedures. The purpose of this study was to quantitatively compare contrast-enhanced ultrasound (CEUS) imaging […]

Bioluminescence Tomography-Guided Radiation Therapy for Preclinical Research

PURPOSE: In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based […]

Proposal for a Simple and Efficient Monthly Quality Management Program Assessing the Consistency of Robotic Image-Guided Small Animal Radiation Systems

Modern pre-clinical radiation therapy (RT) research requires high precision and accurate dosimetry to facilitate the translation of research findings into clinical practice. Several systems are available that provide precise delivery and on-board imaging capabilities, highlighting the need for a quality management program (QMP) to ensure consistent and accurate radiation dose delivery. An ongoing, simple, and […]

microRNA-34a promotes DNA damage and mitotic catastrophe.

Efficient and error-free DNA repair is critical for safeguarding genome integrity, yet it is also linked to radio- and chemoresistance of malignant tumors. miR-34a, a potent tumor suppressor, influences a large set of p53-regulated genes and contributes to p53-mediated apoptosis. However, the effects of miR-34a on the processes of DNA damage and repair are not entirely understood. We explored tet-inducible miR-34a-expressing human p53 wild-type and R273H p53 mutant GBM cell lines, and found [...]

Systemic Tolerance Mediated by Melanoma Brain Tumors Is Reversible by Radiotherapy and Vaccination

PURPOSE: Immune responses to antigens originating in the central nervous system (CNS) are generally attenuated, as collateral damage can have devastating consequences. The significance of this finding for the efficacy of tumor-targeted immunotherapies is largely unknown. EXPERIMENTAL DESIGN: The B16 murine melanoma model was used to compare cytotoxic responses against established tumors in the CNS […]

Selective Inhibition of Parallel DNA Damage Response Pathways Optimizes Radiosensitization of Glioblastoma Stem-like Cells.

Glioblastoma is the most common form of primary brain tumor in adults and is essentially incurable. Despite aggressive treatment regimens centered on radiotherapy, tumor recurrence is inevitable and is thought to be driven by glioblastoma stem-like cells (GSC) that are highly radioresistant. DNA damage response pathways are key determinants of radiosensitivity but the extent to which these overlapping and parallel signaling components contribute to GSC radioresistance is unclear. Using a [...]

Intravesical Liposomal Tacrolimus Protects against Radiation Cystitis Induced by 3-Beam Targeted Bladder Radiation

PURPOSE: We primarily determined whether the small animal radiation research platform could create a rat radiation cystitis model via targeted bladder irradiation (phase I). The response to treating early phase radiation cystitis in rats with transurethral catheter instillation of liposomal tacrolimus was also examined (phase II). MATERIALS AND METHODS: In phase I 16 adult female […]

Identification of suitable endogenous controls for gene and miRNA expression studies in irradiated prostate cancer cells.

This study aimed to to evaluate the stability of commonly used endogenous control genes for messenger RNA (mRNA) (N = 16) and miRNAs (N = 3) expression studies in prostate cell lines following irradiation. The stability of endogenous control genes expression in irradiated (6 Gy) versus unirradiated controls was quantified using NormFinder and coefficient of variation analyses. HPRT1 and 18S were identified as most and least stable endogenous controls, respectively, for mRNA expression [...]

Comprehensive quality assurance phantom for the small animal radiation research platform (SARRP)

PURPOSE: To develop and test the suitability and performance of a comprehensive quality assurance (QA) phantom for the Small Animal Radiation Research Platform (SARRP). METHODS AND MATERIALS: A QA phantom was developed for carrying out daily, monthly and annual QA tasks including: imaging, dosimetry and treatment planning system (TPS) performance evaluation of the SARRP. The […]

Semi-automatic cone beam CT segmentation of in vivo pre-clinical subcutaneous tumours provides an efficient non-invasive alternative for tumour volume measurements

OBJECTIVE: To evaluate the feasibility and accuracy of using cone beam CT (CBCT) scans obtained in radiation studies using the small-animal radiation research platform to perform semi-automatic tumour segmentation of pre-clinical tumour volumes. METHPOD: Volume measurements were evaluated for different anatomical tumour sites, the flank, thigh and dorsum of the hind foot, for a variety […]

Systematic calibration of an integrated x-ray and optical tomography system for preclinical radiation research

PURPOSE: The cone beam computed tomography (CBCT) guided small animal radiation research platform (SARRP) has been developed for focal tumor irradiation, allowing laboratory researchers to test basic biological hypotheses that can modify radiotherapy outcomes in ways that were not feasible previously. CBCT provides excellent bone to soft tissue contrast, but is incapable of differentiating tumors […]

Magnetic nanoparticle hyperthermia enhances radiation therapy: A study in mouse models of human prostate cancer.

PURPOSE: We aimed to characterise magnetic nanoparticle hyperthermia (mNPH) with radiation therapy (RT) for prostate cancer. METHODS: Human prostate cancer subcutaneous tumours, PC3 and LAPC-4, were grown in nude male mice. When tumours measured 150 mm3 magnetic iron oxide nanoparticles (MIONPs) were injected into tumours to a target dose of 5.5 mg Fe/cm3 tumour, and treated 24 h […]

Role of Interleukin-1 in Radiation-Induced Cardiomyopathy

Thoracic X-ray therapy (XRT), used in cancer treatment, is associated with increased risk of heart failure. XRT-mediated injury to the heart induces an inflammatory response leading to cardiomyopathy. The aim of this study was to determine the role of interleukin (IL)-1 in response to XRT injury to the heart and on the cardiomyopathy development in […]

Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer

Immune checkpoint inhibitors result in impressive clinical responses, but optimal results will require combination with each other and other therapies. This raises fundamental questions about mechanisms of non-redundancy and resistance. Here we report major tumour regressions in a subset of patients with metastatic melanoma treated with an anti-CTLA4 antibody (anti-CTLA4) and radiation, and reproduced this […]

MRI-Only Based Radiotherapy Treatment Planning for the Rat Brain on a Small Animal Radiation Research Platform (SARRP).

Computed tomography (CT) is the standard imaging modality in radiation therapy treatment planning (RTP). However, magnetic resonance (MR) imaging provides superior soft tissue contrast, increasing the precision of target volume selection. We present MR-only based RTP for a rat brain on a small animal radiation research platform (SARRP) using probabilistic voxel classification with multiple MR sequences. Six rat heads were imaged, each with one CT and five MR sequences. The MR sequences [...]

Small animal image-guided radiotherapy: status, considerations and potential for translational impact.

Radiation biology is being transformed by the implementation of small animal image-guided precision radiotherapy into pre-clinical research programmes worldwide. We report on the current status and developments of the small animal radiotherapy field, suggest criteria for the design and execution of effective studies and contend that this powerful emerging technology, used in combination with relevant […]

18F-fluoromethylcholine (FCho), 18F-fluoroethyltyrosine (FET), and 18F-fluorodeoxyglucose (FDG) for the discrimination between high-grade glioma and radiation necrosis in rats: A PET study

INTRODUCTION: Discrimination between (high-grade) brain tumor recurrence and radiation necrosis (RN) remains a diagnostic challenge because both entities have similar imaging characteristics on conventional magnetic resonance imaging (MRI). Metabolic imaging, such as positron emission tomography (PET) could overcome this diagnostic dilemma. In this study, we investigated the potential of 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG), O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET), and [...]

Abrogation of radioresistance in glioblastoma stem-like cells by inhibition of ATM kinase.

Resistance to radiotherapy in glioblastoma (GBM) is an important clinical problem and several authors have attributed this to a subpopulation of GBM cancer stem cells (CSCs) which may be responsible for tumour recurrence following treatment. It is hypothesised that GBM CSCs exhibit upregulated DNA damage responses and are resistant to radiation but the current literature is conflicting. We investigated radioresistance of primary GBM cells grown in stem cell conditions (CSC) compared to [...]

Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen

The immune-modulating effects of radiotherapy (XRT) have gained considerable interest recently, and there have been multiple reports of synergy between XRT and immunotherapy. However, additional preclinical studies are needed to demonstrate the antigen-specific nature of radiation-induced immune responses and elucidate potential mechanisms of synergy with immunotherapy. Here, we demonstrate the ability of stereotactic XRT to […]

Image-guided radiotherapy platform using single nodule conditional lung cancer mouse models

Close resemblance of murine and human trials is essential to achieve the best predictive value of animal-based translational cancer research. Kras-driven genetically engineered mouse models of non-small-cell lung cancer faithfully predict the response of human lung cancers to systemic chemotherapy. Owing to development of multifocal disease, however, these models have not been usable in studies […]

Bioluminescence Tomography-Guided Radiation Therapy for Preclinical Research.

In preclinical radiation research, it is challenging to localize soft tissue targets based on cone beam computed tomography (CBCT) guidance. As a more effective method to localize soft tissue targets, we developed an online bioluminescence tomography (BLT) system for small-animal radiation research platform (SARRP). We demonstrated BLT-guided radiation therapy and validated targeting accuracy based on a newly developed reconstruction algorithm.
Zhang B, Wang KK, Yu J, Eslami S, [...]

MRI-guided 3D conformal arc micro-irradiation of a F98 glioblastoma rat model using the Small Animal Radiation Research Platform (SARRP).

Current glioblastoma (GB) small animal models for cranial radiation therapy (RT) use simple single beam technologies, which differ from the advanced conformal image-guided radiation techniques used in clinical practice. This technological disparity presents a major disadvantage for the development of new therapeutic approaches. Hence, we established a F98 GB rat model using magnetic resonance imaging (MRI)-guided three-dimensional (3D)-conformal arc RT with the Small Animal Radiation [...]

PTH1-34 blocks radiation-induced osteoblast apoptosis by enhancing DNA repair through canonical Wnt pathway

Focal radiotherapy for cancer patients has detrimental effects on bones within the radiation field and the primary clinical signs of bone damage include the loss of functional osteoblasts. We reported previously that daily injection of parathyroid hormone (PTH, 1-34) alleviates radiation-induced osteopenia in a preclinical radiotherapy model by improving osteoblast survival. To elucidate the molecular […]

Invariant natural killer T cells regulate anti-tumor immunity by controlling the population of dendritic cells in tumor and draining lymph nodes

BACKGROUND: Invariant natural killer T (iNKT) cells are CD1d-restricted T cells, which respond rapidly to antigen recognition and promote development of anti-tumor immunity in many tumor models. Surprisingly, we previously found that mice deficient in iNKT cells developed spontaneous CD8+ T cells responses partially effective at inhibiting metastases in mice bearing the 4T1 mammary carcinoma, […]

Listeria monocytogenes Dampens the DNA Damage Response.

The DNA damage response (DDR) is an essential signaling pathway that detects DNA lesions, which constantly occur upon either endogenous or exogenous assaults, and maintains genetic integrity. An infection by an invading pathogen is one such assault, but how bacteria impact the cellular DDR is poorly documented. Here, we report that infection with Listeria monocytogenes induces host DNA breaks. Strikingly, the signature response to these breaks is only moderately activated. We uncover the [...]

53BP1 Mediates the Fusion of Mammalian Telomeres Rendered Dysfunctional by DNA-PKcs Loss or Inhibition

Telomere dysfunction promotes genomic instability and carcinogenesis via inappropriate end-to-end chromosomal rearrangements, or telomere fusions. Previous work indicates that the DNA Damage Response (DDR) factor 53BP1 promotes the fusion of telomeres rendered dysfunctional by loss of TRF2, but is dispensable for the fusion of telomeres lacking Pot1 or critically shortened (in telomerase-deficient mice). Here, we […]

TGFβ inhibition prior to hypofractionated radiation enhances efficacy in preclinical models

The immune infiltrate in colorectal cancer has been correlated with outcome, such that individuals with higher infiltrations of T cells have increased survival independent of the disease stage. For patients with lower immune infiltrates, overall survival is limited. Because the patients with colorectal cancer studied have received conventional cancer therapies, these data may indicate that […]

Positron Emission Tomography for Pre-Clinical Sub-Volume Dose Escalation

PURPOSE: This dissertation focuses on establishment of pre-clinical methods facilitating the use of PET imaging for selective sub-volume dose escalation. Specifically the problems addressed are 1.) The difficulties associated with comparing multiple PET images, 2.) The need for further validation of novel PET tracers before their implementation in dose escalation schema and 3.) The lack […]

PTH1-34 Alleviates Radiotherapy-induced Local Bone Loss by Improving Osteoblast and Osteocyte Survival

Cancer radiotherapy is often complicated by a spectrum of changes in the neighboring bone from mild osteopenia to osteoradionecrosis. We previously reported that parathyroid hormone (PTH, 1–34), an anabolic agent for osteoporosis, reversed bone structural deterioration caused by multiple microcomputed tomography (microCT) scans in adolescent rats. To simulate clinical radiotherapy for cancer patients and to […]

Focal radiation therapy combined with 4-1BB activation and CTLA-4 blockade yields long-term survival and a protective antigen-specific memory response in a murine glioma model.

BACKGROUND: Glioblastoma (GBM) is the most common malignant brain tumor in adults and is associated with a poor prognosis. Cytotoxic T lymphocyte antigen -4 (CTLA-4) blocking antibodies have demonstrated an ability to generate robust antitumor immune responses against a variety of solid tumors. 4-1BB (CD137) is expressed by activated T lymphocytes and served as a […]

Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice With Intracranial Gliomas.

Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging [...]

Dietary and sex-specific factors regulate hypothalamic neurogenesis in young adult mice.

The hypothalamus is the central regulator of a broad range of homeostatic and instinctive physiological processes, such as the sleep-wake cycle, food intake, and sexually dimorphic behaviors. These behaviors can be modified by various environmental and physiological cues, although the molecular and cellular mechanisms that mediate these effects remain poorly understood. Recently, it has become clear that both the juvenile and adult hypothalamus exhibit ongoing neurogenesis, which serve to [...]

Preclinical Models for Translational Research Should Maintain Pace With Modern Clinical Practice.

The technical evolution of radiation therapy for brain cancer has improved both the efficacy of individual radiation treatments and patient safety. The advent of computed tomography (CT)-based planning marked an important initial shift toward target-directed treatment (1). Treatment planning accuracy was further increased by fusing CT planning images with positron emission tomography (PET) and magnetic resonance imaging (MRI) scans (2, 3). Additionally, cone beam CT images acquired before [...]

Radiosensitization of Pancreatic Cancer Cells In Vitro and In Vivo through Poly (ADP-ribose) Polymerase Inhibition with ABT-888

OBJECTIVES: To determine whether poly (ADP-ribose) polymerase-1/2 (PARP-1/2) inhibition enhances radiation-induced cytotoxicity of pancreatic adenocarcinoma in vitro and in vivo, and the mechanism by which this occurs. METHODS: Pancreatic carcinoma cells were treated with ABT-888, radiation, or both. In vitro cell viability, apoptosis, and PARP activity were measured. Orthotopic xenografts were generated in athymic mice […]

Preclinical evaluation of the combination of mTOR and proteasome inhibitors with radiotherapy in malignant peripheral nerve sheath tumors

About one half of malignant peripheral nerve sheath tumors (MPNST) have Neurofibromin 1 (NF1) mutations. NF1 is a tumor suppressor gene essential for negative regulation of RAS signaling. Survival for MPNST patients is poor and we sought to identify an effective combination therapy. Starting with the mTOR inhibitors rapamycin and everolimus, we screened for synergy […]

Gold-Loaded Polymeric Micelles for Computed Tomography-Guided Radiation Therapy Treatment and Radiosensitization.

Gold nanoparticles (AuNPs) have generated interest as both imaging and therapeutic agents. AuNPs are attractive for imaging applications since they are nontoxic and provide nearly three times greater X-ray attenuation per unit weight than iodine. As therapeutic agents, AuNPs can sensitize tumor cells to ionizing radiation. To create a nanoplatform that could simultaneously exhibit long circulation times, achieve appreciable tumor accumulation, generate computed tomography (CT) image [...]

Modality comparison for small animal radiotherapy: A simulation study.

Efficient and error-free DNA repair is critical for safeguarding genome integrity, yet it is also linked to radio- and chemoresistance of malignant tumors. miR-34a, a potent tumor suppressor, influences a large set of p53-regulated genes and contributes to p53-mediated apoptosis. However, the effects of miR-34a on the processes of DNA damage and repair are not entirely understood. We explored tet-inducible miR-34a-expressing human p53 wild-type and R273H p53 mutant GBM cell lines, and found [...]

Dose Painting with a Variable Collimator with the Small Animal Radiation Research Platform (SARRP).

The goal of radiation treatment is to irradiate cancer cells (i.e., a target region) without destroying adjacent healthy tissue. Thus, it is advantageous to form the beam so that it best approximates the target, thereby reducing the amount of dose absorbed in critical regions outside the target area. While multi-leaf collimators are common in human clinical systems, small animal radiotherapy systems are typically limited to a set of fixed-size collimators. For these systems, dose painting [...]

Deficiency in Homologous Recombination Renders Mammalian Cells More Sensitive to Proton Versus Photon Irradiation.

Dose measurements in pre-clinical and radiobiology studies are frequently inadequate, thus undermining the reliability and reproducibility of the published findings.
Nicole Grosse, Andrea O Fontana, Eugen B. Hug, Antony Lomax, Adolf Coray, Marc Augsburger, Harald Paganetti, Alessandro A Sartori, and Martin Pruschy
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Quantitative multiparametric MRI assessment of glioma response to radiotherapy in a rat model

BACKGROUND: The inability of structural MRI to accurately measure tumor response to therapy complicates care management for patients with gliomas. The purpose of this study was to assess the potential of several noninvasive functional and molecular MRI biomarkers for the assessment of glioma response to radiotherapy. METHODS: Fourteen U87 tumor-bearing rats were irradiated using a […]

Theranostic gold nanoparticles modified for durable systemic circulation effectively and safely enhance the radiation therapy of human sarcoma cells and tumors

Radiation therapy (RT) is an integral component of the treatment of many sarcomas and relies on accurate targeting of tumor tissue. Despite conventional treatment planning and RT, local failure rates of 10% to 28% at 5 years have been reported for locally advanced, unresectable sarcomas, due in part to limitations in the cumulative RT dose […]

Hematopoietic Stem and Progenitor Cell Migration After Hypofractionated Radiation Therapy in a Murine Model.

To characterize the recruitment of bone marrow (BM)-derived hematopoietic stem and progenitor cells (HSPCs) within tumor microenvironment after radiation therapy (RT) in a murine, heterotopic tumor model.
Jonathan Kane, Sarah A. Krueger, Joshua T. Dilworth, John T. Torma, George D. Wilson, Brian Marples, Gerard J. Madlambayan
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microRNA-34a promotes DNA damage and mitotic catastrophe

Efficient and error-free DNA repair is critical for safeguarding genome integrity, yet it is also linked to radio- and chemoresistance of malignant tumors. miR-34a, a potent tumor suppressor, influences a large set of p53-regulated genes and contributes to p53-mediated apoptosis. However, the effects of miR-34a on the processes of DNA damage and repair are not […]

Functional interrogation of adult hypothalamic neurogenesis with focal radiological inhibition

The functional characterization of adult-born neurons remains a significant challenge. Approaches to inhibit adult neurogenesis via invasive viral delivery or transgenic animals have potential confounds that make interpretation of results from these studies difficult. New radiological tools are emerging, however, that allow one to noninvasively investigate the function of select groups of adult-born neurons through […]

Exposure to hypoxia following irradiation increases radioresistance in prostate cancer cells.

Tumor hypoxia is a common feature of prostate tumors associated with the stabilization of hypoxia-inducible-factor 1alpha (HIF-1α) and poor prognosis following radiation therapy. Lack of oxygen at the time of irradiation is associated with radioresistance, but recent reports suggest radioresponse is also modulated by the dynamic nature of tumor hypoxia.
Derek Hennessey, Lynn Martin, Anne Atzberger, Thomas Lynch, Donal Hollywood and Laure Marignol

Combined treatment effects of radiation and immunotherapy: studies in an autochthonous prostate cancer model.

PURPOSE: To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer. METHODS AND MATERIALS: Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic […]

Proteasome Inhibitors Block DNA Repair and Radiosensitize Non-Small Cell Lung Cancer.

Despite optimal radiation therapy (RT), chemotherapy and/or surgery, a majority of patients with locally advanced non-small cell lung cancer (NSCLC) fail treatment. To identify novel gene targets for improved tumor control, we performed whole genome RNAi screens to identify knockdowns that most reproducibly increase NSCLC cytotoxicity. These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. Radiation and [...]

Inhibition of Hsp27 Radiosensitizes Head-and-Neck Cancer by Modulating Deoxyribonucleic Acid Repair.

To present a novel method of tumor radiosensitization through Hsp27 knockdown using locked nucleic acid (LNA) and to investigate the role of Hsp27 in DNA double strand break (DSB) repair.
David M. Guttmann, Lori Hart, Kevin Du, Andrew Seletsky, Constantinos Koumenis
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Molecularly targeted agents as radiosensitizers in cancer therapy–focus on prostate cancer.

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts […]

DNA mismatch repair protein MSH2 dictates cellular survival in response to low dose radiation in endometrial carcinoma cells.

DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The low-dose radioresponse of MSH2 isogenic endometrial carcinoma cell lines was examined. Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. Maintenance of the arrest was [...]

An integrated x-ray/optical tomography system for pre-clinical radiation research.

The current Small Animal Radiation Research Platform (SARRP) is poor for localizing small soft tissue targets for irradiation or tumor models growing in a soft tissue environment. Therefore, an imaging method complementary to x-ray CT is required to localize the soft tissue target’s Center of Mass (CoM) to within 1 mm. In this paper, we report the development of an integrated x-ray/bioluminescence imaging/tomography (BLI/BLT) system to provide a pre-clinical, high resolution irradiation [...]

Accuracy of off-line bioluminescence imaging to localize targets in preclinical radiation research

In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A small glass bulb containing BL cells was implanted as a BL source in the abdomen […]

High throughput film dosimetry in homogeneous and heterogeneous media for a small animal irradiator

PURPOSE: We have established a high-throughput Gafchromic film dosimetry protocol for narrow kilo-voltage beams in homogeneous and heterogeneous media for small-animal radiotherapy applications. The kV beam characterization is based on extensive Gafchromic film dosimetry data acquired in homogeneous and heterogeneous media. An empirical model is used for parameterization of depth and off-axis dependence of measured […]

An integrated method for reproducible and accurate image guided stereotactic cranial radiation of brain tumors using the small animal radiation research platform.

Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our novel radiation system makes use of magnetic resonance imaging (MRI) and bioluminescent imaging [...]

Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas

PURPOSE: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, and radiation is one of the main treatment modalities. However, cure rates remain low despite best available therapies. Immunotherapy is a promising modality that could work synergistically with radiation, which has been shown to increase antigen presentation and promote a proinflammatory tumor […]

Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells

Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the “non-oncogene” addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded “client” proteins, that is commonly overexpressed in […]

Mechanisms of blood flow and hypoxia production in rat 9L-epigastric tumors

Classical descriptions of tumor physiology suggest two origins for tumor hypoxia; steady-state (diffusion-limited) hypoxia and cycling (perfusion-modulated) hypoxia. Both origins, primarily studied and characterized in murine models, predict relatively small, isolated foci or thin shells of hypoxic tissue interspersed with contrasting oxic tissue. These foci or shells would not be expected to scale with overall […]

Mechanisms of blood flow and hypoxia production in rat 9L-epigastric tumors.

Classical descriptions of tumor physiology suggest two origins for tumor hypoxia; steady-state (diffusion-limited) hypoxia and cycling (perfusionmodulated) hypoxia. Both origins, primarily studied and characterized in murine models, predict relatively small, isolated foci or thin shells of hypoxic tissue interspersed with contrasting oxic tissue. These foci or shells would not be expected to scale with overall tumor size since the oxygen diffusion distance (determined by oxygen permeability [...]

MicroRNA-31 modulates tumour sensitivity to radiation in oesophageal adenocarcinoma.

Chemoradiation therapy (CRT) prior to surgery is increasingly the standard of care for locally advanced oesophageal cancer. Radiation therapy is important for local tumour control; however, tumour resistance to radiation is a substantial clinical problem. The mechanism(s) of radioresistance are still poorly understood, however, mounting evidence supports a role for microRNA (miRNA) in modulating key cellular pathways mediating response to radiation. Global miRNA profiling of an established [...]

Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers

PURPOSE: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. METHODS AND […]

Subventricular zone localized irradiation affects the generation of proliferating neural precursor cells and the migration of neuroblasts

Radiation therapy is a part of the standard treatment for brain tumor patients, often resulting in irreversible neuropsychological deficits. These deficits may be due to permanent damage to the neural stem cell (NSC) niche, damage to local neural progenitors, or neurotoxicity. Using a computed tomography-guided localized radiation technique, we studied the effects of radiation on […]

Tanycytes of the Hypothalamic Median Eminence Form a Diet-Responsive Neurogenic Niche

Adult hypothalamic neurogenesis has been recently reported, but the cell of origin and function of these newborn neurons are unknown. We utilize genetic fate mapping to show that median eminence tanycytes generate newborn neurons; blocking this neurogenesis alters weight and metabolic activity in adult mice. These findings describe a previously unreported neurogenic niche within the […]

Self-calibrated algorithms for diffuse optical tomography and bioluminescence tomography using relative transmission images

Reconstruction algorithms for diffuse optical tomography (DOT) and bioluminescence tomography (BLT) have been developed based on diffusion theory. The algorithms numerically solve the diffusion equation using the finite element method. The direct measurements of the uncalibrated light fluence rates by a camera are used for the reconstructions. The DOT is self-calibrated by using all possible […]

Stereotactic intracranial implantation and in vivo bioluminescent imaging of tumor xenografts in a mouse model system of glioblastoma multiforme

Glioblastoma multiforme (GBM) is a high-grade primary brain cancer with a median survival of only 14.6 months in humans despite standard tri-modality treatment consisting of surgical resection, post-operative radiation therapy and temozolomide chemotherapy. New therapeutic approaches are clearly needed to improve patient survival and quality of life. The development of more effective treatment strategies would […]

Radiation-induced double-strand breaks require ATM but not Artemis for homologous recombination during S-phase.

Double-strand breaks (DSBs) are repaired by two distinct pathways, non-homologous end joining (NHEJ) and homologous recombination (HR). The endonuclease Artemis and the PIK kinase Ataxia-Telangiectasia Mutated (ATM), mutated in prominent human radiosensitivity syndromes, are essential for repairing a subset of DSBs via NHEJ in G1 and HR in G2. Both proteins have been implicated in DNA end resection, a mandatory step preceding homology search and strand pairing in HR. Here, we show that [...]

An Integrated Method for Reproducible and Accurate Image-Guided Stereotactic Cranial Irradiation of Brain Tumors Using the Small Animal Radiation Research Platform

Preclinical studies of cranial radiation therapy (RT) using animal brain tumor models have been hampered by technical limitations in the delivery of clinically relevant RT. We established a bioimageable mouse model of glioblastoma multiforme (GBM) and an image-guided radiation delivery system that facilitated precise tumor localization and treatment and which closely resembled clinical RT. Our […]

A multipurpose quality assurance phantom for the small animal radiation research platform (SARRP).

In this work, the suitability and performance of a mouse-size MOSFET (Mousefet) phantom is investigated for routine quality assurance (QA) of the small animal radiation research platform (SARRP). This Mousefet phantom is a simple construction consisting of five micro-MOSFETS custom integrated in a quincunx pattern within a tissue-equivalent phantom, allowing repeat/multiple QA tasks to be quickly performed in one experimental set-up. The Mousefet phantom is particularly evaluated for [...]

A Treatment Planning System for the Small Animal Radiation Research Platform (SARRP) based on 3D Slicer

This paper describes the software integration of a treatment planning system (TPS), based on the open-source 3D Slicer package, with the Small Animal Radiation Research Platform (SARRP).The TPS is designed to enable researchers to replicate their clinical techniques, allow for image fusion with other imaging modalities, and provide dose computation and graphical visualization of treatment […]

Localized CT-Guided Irradiation Inhibits Neurogenesis in Specific Regions of the Adult Mouse Brain

Radiation is used in the study of neurogenesis in the adult mouse both as a model for patients undergoing radiation therapy for CNS malignancies and as a tool to interrupt neurogenesis. We describe the use of a dedicated CT-guided precision device to irradiate specific sub-regions of the adult mouse brain. Improved CT visualization was accomplished […]

Radiosensitization of Normoxic and Hypoxic H1339 Lung Tumor Cells by Heat Shock Protein 90 Inhibition Is Independent of Hypoxia Inducible Factor-1a.

Ionizing irradiation is a commonly accepted treatment modality for lung cancer patients. However, the clinical outcome is hampered by normal tissue toxicity and tumor hypoxia. Since tumors often have higher levels of active heat shock protein 90 (Hsp90) than normal tissues, targeting of Hsp90 might provide a promising strategy to sensitize tumors towards irradiation. Hsp90 client proteins include oncogenic signaling proteins, cell cycle activators, growth factor receptors and hypoxia [...]

Cellular Autofluorescence following Ionizing Radiation.

Cells often autofluoresce in response to UV radiation excitation and this can reflect critical aspects of cellular metabolism. Here we report that many different human and murine cell types respond to ionizing radiation with a striking rise in autofluorescence that is dependent on dose and time. There was a highly reproducible fluorescent shift at various wavelengths, which was mirrored by an equally reproducible rise in the vital intracellular metabolic co-factors FAD and NADH. It appears [...]

Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer.

Immune checkpoint inhibitors1 result in impressive clinical responses2, 3, 4, 5, but optimal results will require combination with each other6 and other therapies. This raises fundamental questions about mechanisms of non-redundancy and resistance. Here we report major tumour regressions in a subset of patients with metastatic melanoma treated with an anti-CTLA4 antibody (anti-CTLA4) and radiation, and reproduced this effect in mouse models. Although combined treatment improved responses in [...]

A multipurpose quality assurance phantom for the small animal radiation research platform (SARRP)

In this work, the suitability and performance of a mouse-size MOSFET (Mousefet) phantom is investigated for routine quality assurance (QA) of the small animal radiation research platform (SARRP). This Mousefet phantom is a simple construction consisting of five micro-MOSFETS custom integrated in a quincunx pattern within a tissue-equivalent phantom, allowing repeat/multiple QA tasks to be […]

Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.

PURPOSE: We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response. MATERIALS AND METHODS: Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, […]

Delta-Like Ligand 4–Notch Blockade and Tumor Radiation Response.

The microenvironment plays an important role in regulating tumor response to radiotherapy. Ionizing radiation can disrupt tumor vasculature, and Notch pathway inhibition can interfere with functional angiogenesis. We explored the potential cooperativity between Notch inhibition and ionizing radiation in delaying tumor growth.
Stanley K Liu, Saif A S Bham, Emmanouil Fokas, John Beech, Jaehong Im, Song Cho, Adrian L Harris and Ruth J Muschel

Acid Sphingomyelinase Is Required for Protection of Effector Memory T Cells against Glucocorticoid-Induced Cell Death.

The activity of acid sphingomyelinase (aSMase) was previously reported to be involved in glucocorticoid-induced cell death (GICD) of T lymphocytes. This mechanism in turn is believed to contribute to the therapeutic efficacy of glucocorticoids (GCs) in the treatment of inflammatory diseases. In this study, we reassessed the role of aSMase in GICD by using aSMase knockout mice. The absence of aSMase largely abolished the partial protection that effector memory CD4+ T cells in wild-type mice [...]

WAF1/CIP1.

Although caspase-2 represents the most conserved caspase across species and was the second caspase identified, its precise function remains enigmatic. In several cell types we show that knockdown of caspase-2 specifically impaired DNA damage-induced p21 expression, whereas overexpression of a caspase-2 mutant increased p21 levels. Caspase-2 did not influence p21 mRNA transcription; moreover, various inhibitors targeting proteasomal or non-proteasomal proteases, including caspases, could not [...]

MOSFET assessment of radiation dose delivered to mice using the Small Animal Radiation Research Platform (SARRP)

The Small Animal Radiation Research Platform (SARRP) is a novel isocentric irradiation system that enables state-of-the-art image-guided radiotherapy research to be performed with animal models. This paper reports the results obtained from investigations assessing the radiation dose delivered by the SARRP to different anatomical target volumes in mice. Surgically implanted metal oxide semiconductor field effect […]

Impact of oncogenic K-RAS on YB-1 phosphorylation induced by ionizing radiation.

Expression of Y-box binding protein-1 (YB-1) is associated with tumor progression and drug resistance. Phosphorylation of YB-1 at serine residue 102 (S102) in response to growth factors is required for its transcriptional activity and is thought to be regulated by cytoplasmic signaling phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathways. These pathways can be activated by growth factors and by exposure to [...]

A radiotherapy technique to limit dose to neural progenitor cell niches without compromising tumor coverage

Radiation therapy (RT) for brain tumors is associated with neurocognitive toxicity which may be a result of damage to neural progenitor cells (NPCs). We present a novel technique to limit the radiation dose to NPC without compromising tumor coverage. A study was performed in mice to examine the rationale and another was conducted in humans […]

Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells

Radiation therapy can result in bone injury with the development of fractures and often can lead to delayed and nonunion of bone. There is no prevention or treatment for irradiation-induced bone injury. We irradiated the distal half of the mouse left femur to study the mechanism of irradiation-induced bone injury and found that no mesenchymal […]

Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides

It remains difficult to distinguish tumor recurrence from radiation necrosis after brain tumor therapy. Here we show that these lesions can be distinguished using the amide proton transfer (APT) magnetic resonance imaging (MRI) signals of endogenous cellular proteins and peptides as an imaging biomarker. When comparing two models of orthotopic glioma (SF188/V+ glioma and 9L […]

Alterations in DNA Repair Efficiency are Involved in the Radioresistance of Esophageal Adenocarcinoma.

To study radioresistance in esophageal adenocarcinoma, we generated an isogenic cell line model by exposing OE33 esophageal adenocarcinoma cells to clinically relevant fractionated doses of radiation (cumulative dose 50 Gy). A clonogenic assay confirmed enhanced survival of the radioresistant OE33 subline (OE33 R). To our knowledge, we are the first to generate an isogenic model of radioresistance in esophageal adenocarcinoma. This model system was characterized in terms of growth, cell [...]

Irradiation-Induced Up-Regulation of HLA-E on Macrovascular Endothelial Cells Confers Protection against Killing by Activated Natural Killer Cells.

Apart from the platelet/endothelial cell adhesion molecule 1 (PECAM-1, CD31), endoglin (CD105) and a positive factor VIII-related antigen staining, human primary and immortalized macro- and microvascular endothelial cells (ECs) differ in their cell surface expression of activating and inhibitory ligands for natural killer (NK) cells. Here we comparatively study the effects of irradiation on the phenotype of ECs and their interaction with resting and activated NK cells.
Isabelle [...]

Robotic Delivery of Complex Radiation Volumes for Small Animal Research

The Small Animal Radiation Research Platform (SARRP) is a novel and complete system capable of delivering multidirectional (focal), kilo-voltage radiation fields to targets in small animals under robotic control using cone-beam CT (CBCT) image guidance. The capability of the SARRP to deliver highly focused beams to multiple animal models provides new research opportunities that more […]

CT guidance is needed to achieve reproducible positioning of the mouse head for repeat precision cranial irradiation

To study the effects of cranial irradiation, we have constructed an all-plastic mouse bed equipped with an immobilizing head holder. The bed integrates with our in-house Small Animal Radiation Research Platform (SARRP) for precision focal irradiation experiments and cone-beam CT. We assessed the reproducibility of our head holder to determine the need for CT-based targeting […]

Recognition of O6MeG lesions by MGMT and mismatch repair proficiency may be a prerequisite for low-dose radiation hypersensitivity.

Low-dose hyper-radiosensitivity (HRS) is the phenomenon whereby cells exposed to radiation doses of less than ∼0.5 Gy exhibit increased cell killing relative to that predicted from back-extrapolating high-dose survival data using a linear-quadratic model. While the exact mechanism remains to be elucidated, the involvement of several molecular repair pathways has been documented. These processes in turn are also associated with the response of cells to O6-methylguanine (O6MeG) lesions. We [...]

Courtship raises male fertilization success through post-mating sexual selection in a spider.

Courtship is well known for its positive effects on mating success. However, in polyandrous species, sexual selection continues to operate after copulation. Cryptic female choice is expected under unpredictable mating rates in combination with sequential mate encounters. However, there are very few accounts of the effects of courtship on cryptic female choice, and the available evidence is often correlative.
Mature Argiope bruennichi females are always receptive and never attack or [...]

Towards real-time radiation therapy: GPU accelerated superposition/convolution.

We demonstrate the use of highly parallel graphics processing units (GPUs) to accelerate the superposition/convolution (S/C) algorithm to interactive rates while reducing the number of approximations. S/C first transports the incident fluence to compute the total energy released per unit mass (TERMA) grid. Dose is then calculated by superimposing the dose deposition kernel at each […]

A comprehensive system for dosimetric commissioning and Monte Carlo validation for the small animal radiation research platform

Our group has constructed the small animal radiation research platform (SARRP) for delivering focal, kilo-voltage radiation to targets in small animals under robotic control using cone-beam CT guidance. The present work was undertaken to support the SARRP’s treatment planning capabilities. We have devised a comprehensive system for characterizing the radiation dosimetry in water for the […]

Hypoxia response element-driven cytosine deaminase/5-fluorocytosine gene therapy system: a highly effective approach to overcome the dynamics of tumour hypoxia and enhance the radiosensitivity of prostate cancer cells in vitro.

We proposed to exploit hypoxia-inducible factor (HIF)-1alpha overexpression in prostate tumours and use this transcriptional machinery to control the expression of the suicide gene cytosine deaminase (CD) through binding of HIF-1alpha to arrangements of hypoxia response elements. CD is a prodrug activation enzyme, which converts inactive 5-fluorocytosine to active 5-fluorouracil (5-FU), allowing selective killing of vector containing cells.
Laure Marignol, Ruth Foley, Thomas Southgate, [...]

Image Guided Small Animal Radiation Research Platform: Calibration of Treatment Beam Alignment

Small animal research allows detailed study of biological processes, disease progression, and response to therapy, with the potential to provide a natural bridge to the clinical environment. The Small Animal Radiation Research Platform (SARRP) is a portable system for precision irradiation with beam sizes down to approximately 0.5 mm and optimally planned radiation with on-board […]

Precision radiotherapy for small animal research

Preclinical research using well characterized small animal models has provided tremendous benefits to medical research, enabling low cost, large scale trials with high statistical significance of observed effects. The goal of the Small Animal Radiation Research Platform (SARRP) is to make those models available for the development and evaluation of novel radiation therapies. SARRP demonstrates […]

High-resolution, small animal radiation research platform with x-ray tomographic guidance capabilities

PURPOSE: To demonstrate the computed tomography, conformal irradiation, and treatment planning capabilities of a small animal radiation research platform (SARRP). METHODS AND MATERIALS: The SARRP uses a dual-focal spot, constant voltage X-ray source mounted on a gantry with a source-to-isocenter distance of 35 cm. Gantry rotation is limited to 120 degrees from vertical. X-rays of […]

Sertraline slows disease progression and increases neurogenesis in N171-82Q mouse model of Huntington’s disease

Huntington’s disease (HD) is an inherited progressive neurodegenerative disorder resulting from CAG repeat expansion in the gene that encodes for the protein huntingtin. To identify neuroprotective compound (s) that can slow down disease progression and can be administered long term with few side effects in Huntington’s disease, we investigated the effect of sertraline, a selective […]

The small-animal radiation research platform (SARRP): dosimetry of a focused lens system.

A small animal radiation platform equipped with on-board cone-beam CT and conformal irradiation capabilities is being constructed for translational research. To achieve highly localized dose delivery, an x-ray lens is used to focus the broad beam from a 225 kVp x-ray tube down to a beam with a full width half maximum (FWHM) of approximately […]

Small animal radiation research platform: imaging, mechanics, control and calibration

In cancer research, well characterized small animal models of human cancer, such as transgenic mice, have greatly accelerated the pace of development of cancer treatments. The goal of the Small Animal Radiation Research Platform (SARRP) is to make those same models available for the development and evaluation of novel radiation therapies. In combination with advanced […]

Addendum to the IPEMB code of practice for the determination of absorbed dose for x-rays below 300 kV generating potential (0.035 mm Al–4 mm Cu HVL)

This addendum to the code of practice for the determination of absorbed dose for x-rays below 300 kV has recently been approved by the IPEM and introduces three main changes: (i) Due to a lack of available data the original code recommended a value of unity for kch in the very-low-energy range (0.035–1.0 mm Al HVL). A single table of kch values, ranging from 1.01 to 1.07, applicable to both designated chamber types is now presented. (ii) For medium-energy x-rays (0.5–4 mm Cu HVL) methods [...]

The IPEMB code of practice for the determination of absorbed dose for x-rays below 300 kV generating potential (0.035 mm Al – 4 mm Cu HVL; 10 – 300 kV generating potential)

This new code of practice for the determination of absorbed dose for x-rays below 300 kV has recently been approved by the IPEMB and introduces the following changes to the previous codes: (i) The determination of absorbed dose is based on the air kerma determination (exposure measurement) method. (ii) An air kerma calibration factor for the ionization chamber is used. (iii) The use of the F (rad/röentgen) conversion factor is abandoned and replaced by the ratio of the mass - energy [...]

AAPM protocol for 40–300 kV x-ray beam dosimetry in radiotherapy and radiobiology

The American Association of Physicists in Medicine (AAPM) presents a new protocol, developed by the Radiation Therapy Committee Task Group 61, for reference dosimetry of low- and medium-energy x rays for radiotherapy and radiobiology math formula It is based on ionization chambers calibrated in air in terms of air kerma. If the point of interest is at or close to the surface, one unified approach over the entire energy range shall be used to determine absorbed dose to water at the surface [...]

Proposal for a Simple and Efficient Monthly Quality Management Program Assessing the Consistency of Robotic Image-Guided Small Animal Radiation Systems

Modern pre-clinical radiation therapy (RT) research requires high precision and accurate dosimetry to facilitate the translation of research findings into clinical practice. Several systems are available that provide precise delivery and on-board imaging capabilities, highlighting the need for a quality management program (QMP) to ensure consistent and accurate radiation dose delivery. An ongoing, simple, and […]

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