Journal articles on the topic 'Non-targeted effect in radiotherapy'
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Sjostedt, Svetlana, and Eva Bezak. "Non-targeted effects of ionising radiation and radiotherapy." Australasian Physical & Engineering Sciences in Medicine 33, no. 3 (September 2010): 219–31. http://dx.doi.org/10.1007/s13246-010-0030-8.
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Rita, Ghosh, and Hansda Surajit. "Targeted and non-targeted effects of radiation in mammalian cells: An overview." Archives of Biotechnology and Biomedicine 5, no. 1 (April 12, 2021): 013–19. http://dx.doi.org/10.29328/journal.abb.1001023.
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Radiation of different wavelengths can kill living organisms, although, the mechanism of interactions differs depending on their energies. Understanding the interaction of radiation with living cells is important to assess their harmful effects and also to identify their therapeutic potential. Temporally, this interaction can be broadly divided in three stages – physical, chemical and biological. While radiation can affect all the important macromolecules of the cells, particularly important is the damage to its genetic material, the DNA. The consequences of irradiation include- DNA damage, mutation, cross-linkages with other molecules, chromosomal aberrations and DNA repair leading to altered gene expression and/or cell death. Mutations in DNA can lead to heritable changes and is important for the induction of cancer. While some of these effects are through direct interaction of radiation with the target, radiation can interact with the surrounding environment to result in its indirect actions. The effects of radiation depend not only on the total dose but also on the dose rate, LET etc. and also on the cell types. However, action of radiation on organisms is not restricted to interactions with irradiated cells, i.e. target cells alone; it also exerts non-targeted effects on neighboring unexposed cells to produce productive responses; this is known as bystander effect. The bystander effects of ionizing radiations are well documented and contribute largely to the relapse of cancer and secondary tumors after radiotherapy. Irradiation of cells with non-ionizing Ultra-Violet light also exhibits bystander responses, but such responses are very distinct from that produced by ionizing radiations.
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Fernandez-Palomo, Cristian, Zacharenia Nikitaki, Valentin Djonov, Alexandros G. Georgakilas, and Olga A. Martin. "Non-Targeted Effects of Synchrotron Radiation: Lessons from Experiments at the Australian and European Synchrotrons." Applied Sciences 12, no. 4 (February 17, 2022): 2079. http://dx.doi.org/10.3390/app12042079.
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Studies have been conducted at synchrotron facilities in Europe and Australia to explore a variety of applications of synchrotron X-rays in medicine and biology. We discuss the major technical aspects of the synchrotron irradiation setups, paying specific attention to the Australian Synchrotron (AS) and the European Synchrotron Radiation Facility (ESRF) as those best configured for a wide range of biomedical research involving animals and future cancer patients. Due to ultra-high dose rates, treatment doses can be delivered within milliseconds, abiding by FLASH radiotherapy principles. In addition, a homogeneous radiation field can be spatially fractionated into a geometric pattern called microbeam radiotherapy (MRT); a coplanar array of thin beams of microscopic dimensions. Both are clinically promising radiotherapy modalities because they trigger a cascade of biological effects that improve tumor control, while increasing normal tissue tolerance compared to conventional radiation. Synchrotrons can deliver high doses to a very small volume with low beam divergence, thus facilitating the study of non-targeted effects of these novel radiation modalities in both in-vitro and in-vivo models. Non-targeted radiation effects studied at the AS and ESRF include monitoring cell–cell communication after partial irradiation of a cell population (radiation-induced bystander effect, RIBE), the response of tissues outside the irradiated field (radiation-induced abscopal effect, RIAE), and the influence of irradiated animals on non-irradiated ones in close proximity (inter-animal RIBE). Here we provide a summary of these experiments and perspectives on their implications for non-targeted effects in biomedical fields.
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Mairs, Robert J., Natasha E. Fullerton, Michael R. Zalutsky, and Marie Boyd. "Targeted Radiotherapy: Microgray Doses and the Bystander Effect." Dose-Response 5, no. 3 (July 1, 2007): dose—response.0. http://dx.doi.org/10.2203/dose-response.07-002.mairs.
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Indirect effects may contribute to the efficacy of radiotherapy by sterilizing malignant cells that are not directly irradiated. However, little is known of the influence of indirect effects in targeted radionuclide treatment. We compared γ-radiation-induced bystander effects with those resulting from exposure to three radiohaloanalogues of meta-iodobenzylguanidine (MIBG): [131I]MIBG (low linear energy transfer (LET) β-emitter), [123I]MIBG (high LET Auger electron emitter), and meta-[211At]astatobenzylguanidine ([211At]MABG) (high LET α-emitter). Cells exposed to media from γ-irradiated cells exhibited a dose-dependent reduction in survival fraction at low dosage and a plateau in cell kill at > 2 Gy. Cells treated with media from [131I]MIBG demonstrated a dose-response relationship with respect to clonogenic cell death and no annihilation of this effect at high radiopharmaceutical dosage. In contrast, cells receiving media from cultures treated with [211At]MABG or [123I]MIBG exhibited dose-dependent toxicity at low dose but elimination of cytotoxicity with increasing radiation dose (i.e. U-shaped survival curves). Therefore radionuclides emitting high LET radiation may elicit toxic or protective effects on neighboring untargeted cells at low and high dose respectively. We conclude that radiopharmaceutical-induced bystander effects may depend on LET and be distinct from those elicited by conventional radiotherapy.
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Jokar, Safura, Inês A. Marques, Saeedeh Khazaei, Tania Martins-Marques, Henrique Girao, Mafalda Laranjo, and Maria Filomena Botelho. "The Footprint of Exosomes in the Radiation-Induced Bystander Effects." Bioengineering 9, no. 6 (May 31, 2022): 243. http://dx.doi.org/10.3390/bioengineering9060243.
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Radiation therapy is widely used as the primary treatment option for several cancer types. However, radiation therapy is a nonspecific method and associated with significant challenges such as radioresistance and non-targeted effects. The radiation-induced non-targeted effects on nonirradiated cells nearby are known as bystander effects, while effects far from the ionising radiation-exposed cells are known as abscopal effects. These effects are presented as a consequence of intercellular communications. Therefore, a better understanding of the involved intercellular signals may bring promising new strategies for radiation risk assessment and potential targets for developing novel radiotherapy strategies. Recent studies indicate that radiation-derived extracellular vesicles, particularly exosomes, play a vital role in intercellular communications and may result in radioresistance and non-targeted effects. This review describes exosome biology, intercellular interactions, and response to different environmental stressors and diseases, and focuses on their role as functional mediators in inducing radiation-induced bystander effect (RIBE).
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Trott, Klaus-Rüdiger. "Non-Targeted Radiation Effects in Radiotherapy &Roles of Radiation-Induced Genomic Instability and of the Bystander Effect in Cancer Cure by Radiotherapy." Acta Oncologica 40, no. 8 (January 2001): 976–80. http://dx.doi.org/10.1080/02841860152708260.
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Dams, Ritchell van, Ye Yuan, Clifford G. Robinson, and Percy Lee. "Immunotherapy and Radiation Therapy for Non-Small Cell Lung Cancer—A Stimulating Partnership." Seminars in Respiratory and Critical Care Medicine 41, no. 03 (May 25, 2020): 360–68. http://dx.doi.org/10.1055/s-0039-3399578.
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AbstractNon-small cell lung cancer (NSCLC) is the most common subtype of lung cancer and the leading cause of cancer-related death. Although durable local control rates are high after surgical resection or definitive radiotherapy for early-stage disease, a substantial proportion of these patients eventually experience regional and/or distant failure and succumb to their metastatic disease. The discovery of immunotherapeutics and targeted biologics has revolutionized the treatment of locally advanced and metastatic disease, improving progression-free and overall survival when incorporated with the current standards of care. Notably, post-hoc analyses and early clinical trials provide a growing body of evidence to support a synergistic effect between radiation and immunotherapy for the treatment of NSCLC from early-stage to metastatic disease. Radiotherapy appears to be capable of not only potentiating the effect of immunotherapy in targeted lesions, but also eliciting an antitumor response in distant lesions without any direct exposure to radiation. This review explores the biologic basis of immunotherapy, targeted biologics, and radiotherapy as well as the preclinical and clinical data that support the combined use of radioimmunotherapy for early-stage, locally advanced, and metastatic NSCLC.
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Mohd Zainudin, Nur Hamizah, Noor Nabilah Talik Sisin, Khairunisak Ab Razak, Reduan Abdullah, and Wan Nordiana Rahman. "Evaluation of Bismuth Oxide Nanoparticles (BiONPs) as a Safe Radiobiological Enhancer for Breast Cancer Radiotherapy." Asian Journal of Medicine and Biomedicine 6, S1 (November 4, 2022): 45–47. http://dx.doi.org/10.37231/ajmb.2022.6.s1.522.
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Cancer incidence has been increasing over the years and it is the second leading cause of death globally [1]. The therapeutic strategies in killing the cancerous tissue while keeping the normal healthy tissue uninterrupted can be further improved by introducing nanoparticles (NPs) as radiosensitizers in radiotherapy. In pre-clinical research, a few nanoparticle elements had shown the potential to be radiosensitizers, such as gold, superparamagnetic iron oxide, platinum, and bismuth nanoparticles. Bismuth oxide nanoparticles (BiONPs) have been investigated as a potential radiosensitizer in radiotherapy due to their least toxic and biocompatibility properties. In addition, due to the presence of metallic nanoparticles in cells and their environment, more DNA damage will be introduced and thus enhance the radiation treatment efficacy.
This research project was conducted to evaluate the potential of BiONPs to increase the radiation treatment in MCF-7 breast cancer cells and their side effects on the non-targeted breast cancer cells. BiONPs were synthesized through the hydrothermal method, as established in the previous study [2]. The treated and control cells in flasks were irradiated with radiation doses between 0 to 12 Gy at a constant dose rate of 300 cGy/minutes in the beam field size of 10 cm x 10 cm for a 6 MV photon beam, delivered with linear accelerator Primus model (Siemen Healthcare, USA). The irradiated cell-conditioned medium (ICCM) was collected from the targeted cells and transferred into the non-targeted cells. The cell viability assay was employed to evaluate the effect of BiONPs on directly irradiated and non-irradiated cells.
In our prior work, the BiONPs had shown to boost radiosensitisation effects in treated cells compared to control cells, with a sensitisation enhancement ratio (SER) of 1.38 [3], as shown in Figure 1. The increased radiosensitisation effects might be attributed to the characteristics of BiONPs with a high effective atomic number (Z=83), which promotes radiation interaction, mainly radiation absorption and scattering. Meanwhile, the present study demonstrated that the non-irradiated MCF-7 cells could maintain their cell viability for more than 80% after 48 h incubation with ICCM treated with BiONPs at 2, 6, and 12 Gy. Furthermore, a comparable trend in cell viability was observed in non-irradiated MCF-7 cells for treated and control groups (p<0.05), as illustrated in Figure 2. This finding indicated that BiONPs are not harmful and do not contribute to side effects in non-targeted cells.
The present works have provided evidence that using BiONPs as radiosensitizers in radiotherapy is safe and does not significantly introduce side effects in the non-targeted cells. These data proved the impacts of BiONPs as a potential tool for a safe radiobiological enhancer that will benefit future radiation therapy strategies in cancer management.
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Arslan, Nazmiye Deniz, Sedef Dağ, Ayşe Kutluhan Doğan, Nesrin Gürçay, Hüseyin Özkurt, and Burçak Yılmaz. "Regression of Hypermetabolic Splenic Granulomata Mimicking Metastases Following Non-targeted Effect of Radiotherapy for Uterine Cervical Carcinoma." Cam and Sakura Medical Journal 1, no. 1 (April 1, 2021): 37–42. http://dx.doi.org/10.4274/csmedj.galenos.2021.2021-8-6.
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Xing, Daniel Tao, Richard Khor, Hui Gan, Morikatsu Wada, Tai Ermongkonchai, and Sweet Ping Ng. "Recent Research on Combination of Radiotherapy with Targeted Therapy or Immunotherapy in Head and Neck Squamous Cell Carcinoma: A Review for Radiation Oncologists." Cancers 13, no. 22 (November 15, 2021): 5716. http://dx.doi.org/10.3390/cancers13225716.
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Radiotherapy plays an important role of managing head and neck squamous cell carcinoma (HNSCC). Concurrent radiotherapy with radiosensitizing cisplastin chemotherapy is the standard of care (SOC) for non-operable locally advanced HNSCC. Cetuximab, a monoclonal antibody of epidermal growth factor receptor, was the most extensively studied targeted therapy as a chemo-sparing agent that was used concurrently with radiotherapy. Immunotherapy is used in the treatment of metastatic HNSCC. There is evidence to support the synergistic effect when combining radiotherapy with immunotherapy to potentiate anti-tumor immune response. There has been increasing interest to incorporate immune checkpoint inhibitor (ICI) with radiotherapy in the curative setting for HNSCC. In this review, we discuss the latest evidence that supports concurrent radiotherapy with cisplatin which remains the SOC for locally advanced HNSCC (LA-HNSCC). Cetuximab is suitable for patients who are not fit for cisplatin. We then summarize the clinical trials that incorporate ICI with radiotherapy for LA-HNSCC in concurrent, neoadjuvant, and adjuvant settings. We also discuss the potential of combining immunotherapy with radiotherapy as a treatment de-escalating strategy in HPV-associated oropharyngeal carcinoma. Finally, the pre-clinical and clinical evidence of the abscopal effect when combining stereotactic body radiotherapy with ICIs is presented.
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Yahyapour, Rasoul, Elahe Motevaseli, Abolhasan Rezaeyan, Hamid Abdollahi, Bagher Farhood, Mohsen Cheki, Masoud Najafi, and Vilmar Villa. "Mechanisms of Radiation Bystander and Non-Targeted Effects: Implications to Radiation Carcinogenesis and Radiotherapy." Current Radiopharmaceuticals 11, no. 1 (April 4, 2018): 34–45. http://dx.doi.org/10.2174/1874471011666171229123130.
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Vaidya, Jayant S., Max Bulsara, Christobel Saunders, Henrik Flyger, Jeffrey S. Tobias, Tammy Corica, Samuele Massarut, et al. "Effect of Delayed Targeted Intraoperative Radiotherapy vs Whole-Breast Radiotherapy on Local Recurrence and Survival." JAMA Oncology 6, no. 7 (July 9, 2020): e200249. http://dx.doi.org/10.1001/jamaoncol.2020.0249.
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Apilan, Alyssa Gabrielle, and Carmel Mothersill. "Targeted and Non-Targeted Mechanisms for Killing Hypoxic Tumour Cells—Are There New Avenues for Treatment?" International Journal of Molecular Sciences 22, no. 16 (August 11, 2021): 8651. http://dx.doi.org/10.3390/ijms22168651.
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Purpose: A major issue in radiotherapy is the relative resistance of hypoxic cells to radiation. Historic approaches to this problem include the use of oxygen mimetic compounds to sensitize tumour cells, which were unsuccessful. This review looks at modern approaches aimed at increasing the efficacy of targeting and radiosensitizing hypoxic tumour microenvironments relative to normal tissues and asks the question of whether non-targeted effects in radiobiology may provide a new “target”. Novel techniques involve the integration of recent technological advancements such as nanotechnology, cell manipulation, and medical imaging. Particularly, the major areas of research discussed in this review include tumour hypoxia imaging through PET imaging to guide carbogen breathing, gold nanoparticles, macrophage-mediated drug delivery systems used for hypoxia-activate prodrugs, and autophagy inhibitors. Furthermore, this review outlines several features of these methods, including the mechanisms of action to induce radiosensitization, the increased accuracy in targeting hypoxic tumour microenvironments relative to normal tissue, preclinical/clinical trials, and future considerations. Conclusions: This review suggests that the four novel tumour hypoxia therapeutics demonstrate compelling evidence that these techniques can serve as powerful tools to increase targeting efficacy and radiosensitizing hypoxic tumour microenvironments relative to normal tissue. Each technique uses a different way to manipulate the therapeutic ratio, which we have labelled “oxygenate, target, use, and digest”. In addition, by focusing on emerging non-targeted and out-of-field effects, new umbrella targets are identified, which instead of sensitizing hypoxic cells, seek to reduce the radiosensitivity of normal tissues.
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Bayoumi, Noha Anwer, and Mohamed Taha El-Kolaly. "Utilization of nanotechnology in targeted radionuclide cancer therapy: monotherapy, combined therapy and radiosensitization." Radiochimica Acta 109, no. 6 (April 5, 2021): 459–75. http://dx.doi.org/10.1515/ract-2020-0098.
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Abstract The rapid progress of nanomedicine field has a great influence on the different tumor therapeutic trends. It achieves a potential targeting of the therapeutic agent to the tumor site with neglectable exposure of the normal tissue. In nuclear medicine, nanocarriers have been employed for targeted delivery of therapeutic radioisotopes to the malignant tissues. This systemic radiotherapy is employed to overcome the external radiation therapy drawbacks. This review overviews studies concerned with investigation of different nanoparticles as promising carriers for targeted radiotherapy. It discusses the employment of different nanovehicles for achievement of the synergistic effect of targeted radiotherapy with other tumor therapeutic modalities such as hyperthermia and photodynamic therapy. Radiosensitization utilizing different nanosensitizer loaded nanoparticles has also been discussed briefly as one of the nanomedicine approach in radiotherapy.
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Sager, Omer, Ferrat Dincoglan, Selcuk Demiral, and Murat Beyzadeoglu. "Potential Utility of Radiopharmaceuticals in the Battle Against SARS- Cov- -2 and COVID-19 Pandemic." Current Radiopharmaceuticals 15, no. 2 (June 2022): 93–95. http://dx.doi.org/10.2174/1874471014666211011122250.
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: Coronavirus disease 2019 (COVID-19) pandemic, which has emerged in December 2019 in the city of Wuhan, China, has significantly affected healthcare systems and economies within a short timeframe. Treatment strategies offer alleviation of symptoms in the absence of commercially available specific antiviral agents. Within this context, the introduction of innovative therapeutic approaches against the SARS-CoV-2 virus is a critical need that should be addressed urgently. The anti-inflammatory effect of low dose irradiation has been proposed as a potential therapeutic strategy for COVID-19 pneumonia. Consideration of external beam irradiation for management of COVID-19 pneumonia has prompted the investigation of alternative methods of irradiation with potentially improved toxicity profiles. Theoretically, targeted radiotherapy may have several advantages over conventional external beam radiotherapy owing to the capability to deliver effective radiation doses without adverse irradiation effects. Since radionuclides are conjugated to targeting vectors, such as antibodies and cell surface receptor binding peptides, irradiation may be focused on targeted cells with optimal sparing of surrounding normal tissues. In the context of COVID-19 management, targeted irradiation is expected to compromise SARS-CoV-2 extracellular virions. Targeted radiotherapy may offer a viable means of combating against SARS-CoV-2 virus. There is room for improvement with the need for efficacy, feasibility, and toxicity studies. Although targeted radiotherapy itself may not achieve absolute eradication of virus or virus-infected cells, it may at least serve as a supplementary therapeutic strategy that could be utilized in combination with other antiviral treatments. Further investigations focusing on nuclear medicine, radiopharmaceuticals, and targeted radiotherapy strategies may pave the way for the development of efficacious antiviral treatments which may be utilized in the battle against the current COVID-19 pandemic.
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Antoni, Delphine, Hélène Burckel, and Georges Noel. "Combining Radiation Therapy with ALK Inhibitors in Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer (NSCLC): A Clinical and Preclinical Overview." Cancers 13, no. 10 (May 15, 2021): 2394. http://dx.doi.org/10.3390/cancers13102394.
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Over the past years, the identification of genetic alterations in oncogenic drivers in non-small cell lung cancer (NSCLC) has significantly and favorably transformed the outcome of patients who can benefit from targeted therapies such as tyrosine kinase inhibitors. Among these genetic alterations, anaplastic lymphoma kinase (ALK) rearrangements were discovered in 2007 and are present in 3–5% of patients with NSCLC. In addition, radiotherapy remains one of the cornerstones of NSCLC treatment. Moreover, improvements in the field of radiotherapy with the use of hypofractionated or ablative stereotactic radiotherapy have led to a better outcome for localized or oligometastatic NSCLC. To date, the effects of the combination of ALK inhibitors and radiotherapy are unclear in terms of safety and efficacy but could potently improve treatment. In this manuscript, we provide a clinical and preclinical overview of combining radiation therapy with ALK inhibitors in anaplastic lymphoma kinase-positive non-small cell lung cancer.
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Du, Yan, and Yong Zeng. "Analysis of postoperative radiotherapy for non-metastatic head and neck adenoid cystic carcinoma based on SEER data." Journal of International Medical Research 50, no. 8 (August 2022): 030006052211151. http://dx.doi.org/10.1177/03000605221115151.
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Objective The postoperative role of adjuvant radiotherapy in non-metastatic head and neck adenoid cystic carcinoma (ACC) remains controversial. We analyzed adjuvant radiotherapy’s effect on surgical patient survival. Methods Patients diagnosed with ACC from 2004 to 2015 in the Surveillance, Epidemiology, and End Results database were analyzed. The overall survival (OS) and disease-specific survival (DSS) of patients after adjuvant radiotherapy were assessed using the Kaplan–Meier and multivariate Cox methods. Propensity score matching (PSM) was performed to adjust confounders between patients with or without adjuvant radiotherapy; a forest plot was generated by subgroup analysis. Results The study included 742 patients. In the PSM cohort, adjuvant radiotherapy did not improve OS or DSS. Radiotherapy was not a protective factor for OS or DSS in the univariate and multivariate Cox proportional hazard models. In the subgroup analysis, postoperative radiotherapy improved the OS of female and N1-stage patients and those with oropharyngeal tumors or over 79 years and the DSS of N1-stage patients. Conclusions Postoperative radiotherapy showed different benefits in ACC patients, and postoperative radiotherapy recommendations should be individualized. Female and N1-stage ACC patients and those with oropharyngeal tumors or patients over 79 years without distant metastases postoperatively could benefit from adjuvant radiotherapy.
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Wang, Yuexuan, Yu Han, Yuzhen Jin, Qiang He, and Zhicheng Wang. "The Advances in Epigenetics for Cancer Radiotherapy." International Journal of Molecular Sciences 23, no. 10 (May 18, 2022): 5654. http://dx.doi.org/10.3390/ijms23105654.
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Cancer is an important factor threatening human life and health; in recent years, its morbidity and mortality remain high and demosntrate an upward trend. It is of great significance to study its pathogenesis and targeted therapy. As the complex mechanisms of epigenetic modification has been increasingly discovered, they are more closely related to the occurrence and development of cancer. As a reversible response, epigenetic modification is of great significance for the improvement of classical therapeutic measures and the discovery of new therapeutic targets. It has become a research focusto explore the multi-level mechanisms of RNA, DNA, chromatin and proteins. As an important means of cancer treatment, radiotherapy has made great progress in technology, methods, means and targeted sensitization after years of rapid development, and even research on radiotherapy based on epigenetic modification is rampant. A series of epigenetic effects of radiation on DNA methylation, histone modification, chromosome remodeling, RNA modification and non-coding RNA during radiotherapy affects the therapeutic effects and prognosis. Starting from the epigenetic mechanism of tumorigenesis, this paper reviews the latest progress in the mechanism of interaction between epigenetic modification and cancer radiotherapy and briefly introduces the main types, mechanisms and applications of epigenetic modifiers used for radiotherapy sensitization in order to explore a more individual and dynamic approach of cancer treatment based on epigenetic mechanism. This study strives to make a modest contribution to the progress of human disease research.
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Torrisi, Filippo, Luigi Minafra, Francesco P. Cammarata, Gaetano Savoca, Marco Calvaruso, Nunzio Vicario, Laura Maccari, et al. "SRC Tyrosine Kinase Inhibitor and X-rays Combined Effect on Glioblastoma Cell Lines." International Journal of Molecular Sciences 21, no. 11 (May 30, 2020): 3917. http://dx.doi.org/10.3390/ijms21113917.
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Glioblastoma (GBM) is one of the most lethal types of tumor due to its high recurrence level in spite of aggressive treatment regimens involving surgery, radiotherapy and chemotherapy. Hypoxia is a feature of GBM, involved in radioresistance, and is known to be at the origin of treatment failure. The aim of this work was to assess the therapeutic potential of a new targeted c-SRC inhibitor molecule, named Si306, in combination with X-rays on the human glioblastoma cell lines, comparing normoxia and hypoxia conditions. For this purpose, the dose modifying factor and oxygen enhancement ratio were calculated to evaluate the Si306 radiosensitizing effect. DNA damage and the repair capability were also studied from the kinetic of γ-H2AX immunodetection. Furthermore, motility processes being supposed to be triggered by hypoxia and irradiation, the role of c-SRC inhibition was also analyzed to evaluate the migration blockage by wound healing assay. Our results showed that inhibition of the c-SRC protein enhances the radiotherapy efficacy both in normoxic and hypoxic conditions. These data open new opportunities for GBM treatment combining radiotherapy with molecularly targeted drugs to overcome radioresistance.
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David, Steven, Jennifer Tan, Shankar Siva, Lama Karroum, Peter Savas, and Sherene Loi. "Combining Radiotherapy and Immunotherapy in Metastatic Breast Cancer: Current Status and Future Directions." Biomedicines 10, no. 4 (March 31, 2022): 821. http://dx.doi.org/10.3390/biomedicines10040821.
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The role of radiotherapy and immunotherapy with immune checkpoint inhibitors (ICI) is of emerging interest in many solid tumours, including breast cancer. There is increasing evidence that the host’s immune system plays an important role in influencing the response to treatment and prognosis in breast cancer. Several pre-clinical studies and clinical trials have reported on the ‘abscopal effect—regression of distant untreated tumour sites, mediated by an immunological response following ionizing radiation to a targeted tumour site. Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive technique used to augment various immune responses with an ablative tumoricidal dose when compared to conventional radiotherapy. SABR is characterized by typically 1–5 precision radiotherapy treatments that simultaneously deliver a high dose, whilst sparing normal tissues. Following SABR, there is evidence of systemic immune activation in patients with increased PD1 expression on CD8+ and CD4+ T cells. Studies continue to focus on metastatic triple-negative disease, a highly immunogenic subtype of breast cancer with poor prognosis. In this review, we discuss the immunological effect of SABR, alone and in combination with immunotherapy, and the importance of dose and fractionation. We also propose future strategies for treating oligometastatic disease, where this approach may be most useful for producing durable responses.
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Jafri, Syed Imran Mustafa, Faizan Malik, Naveed Ali, Mary Naglak, and Mark L. Sundermeyer. "Immunotherapy in non-small cell lung cancer and the abscopal effect." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e18104-e18104. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e18104.
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e18104 Background: Advanced research and better understanding of the human immune system has led to the development of targeted immunotherapy such as PD-1 inhibitors. We studied patients with both squamous and non-squamous Non-Small Cell Lung Cancer in a community setting who are being treated with Nivolumab. Our primary objective was to determine response to therapy (overall response rate-ORR). Our secondary objective was to study the abscopal response of our population and if the tumor response was better in those patients who received radiotherapy in the preceding 6 months of the start of immunotherapy Methods: Data were summarized using descriptive statistics including means, standard deviations, medians, frequencies and percentages. Chi square analyses were used to make comparisons between response and categorical variables. Overall response rate was calculated by combining people with partial and complete response. All p-values were two tailed and a level of ≤ 0.05 was considered significant. Results: Out of 21 patients, eight (38%) did not show any disease progression. Five out of these eight patients (23% of total study population) had stable disease. Three remaining patients had partial response to the treatment. The ORR was 14% which is comparable to 20% and 19% ORR in the CheckMate trials for nivolumab. Thirteen (62%) patients had progressive disease. Our study showed no significant effect of radiotherapy on disease response to nivolumab. There was one incidence of treatment discontinuation permanently due to the side effects of Nivolumab. Conclusions: Immunotherapy is a promising new option in lung cancer treatment. Fewer side effects and improved survival compared to traditional second line chemotherapy makes it more appealing. In our study group, nivolumab has shown ORR of 14% and stable disease in an additional 23% of the patients resulting in a disease control rate of 37%.
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Iczkowski, Kenneth A. "Effect of Radiotherapy on Non-Neoplastic and Malignant Prostate." Open Pathology Journal 3, no. 2 (September 8, 2009): 64–73. http://dx.doi.org/10.2174/1874375700903020064.
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Duan, Xiaotong, Xiaoxia Zhu, and Lijuan Wang. "A prospective data analysis of targeted therapy combined with concurrent radiation therapy for brain metastasis from NSCLC with driver gene mutation." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): e14006-e14006. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e14006.
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e14006 Background: Previous studies have shown that brain metastases of non-small cell lung cancer (NSCLC) with positive driver genes have poor prognosis. There is still lack of prospective studies on the efficacy and safety of targeted therapy combined with concurrent radiotherapy for brain metastases(BM). Methods: NSCLC patients, with ECOG score 0-2, having MRI confirmed brain or meningeal metastases were eligible. Patients must have driver gene mutation and received corresponding targeted therapy. The intracranial radiotherapy regimen was SRS or whole brain radiotherapy. The primary objective was iPFS (intracranial progression-free survival); Secondary objectives were: iORR (intracranial objective response rate), PFS (progression-free survival), OS (overall survival). MMSE (Mini Mental State Examination) and FACT-Br was carried out before/after weekly radiotherapy and during systematic treatment. Treatment-related toxicities were assessed according RTOG/EORTC criteria. Tumor responses were evaluated using RECIST V1.1 criteria. Survival analysis was performed using the Graphprism version 6.0 by Kaplan-Meier method and log-rank test. Results: 23 NSCLC with BM was included. Among them, 10 patients were newly diagnosed with NSCLC BM. 2 patients’ BM progressed after targeted therapy. 11 NSCLC patients were newly diagnosed with BM after targeted therapy. 91.3% of patients presented an EGFR mutation, including primarily EGFR 19-exon deletion, EGFR 21-L8585R. 11.5% presented with c-MET mutation. Median age was 58.34 yrs(44-71yrs). Patients were mostly treated with Erolotinib and Gefitinib. All patients were adenocarcinoma. At last follow-up, for patients newly diagnosed with NSCLC BM, 8 patients had achieved intracranial progression, and 7 patients had reached OS, of which 1 died before completing WBRT. The median iPFS was 9.3m(95%CI:0.571-4.055) and the median OS was 11.9m (95%CI:0.2752 -2.732). As for patients who progressed after targeted therapy, one patient’s OS was 4.4m, iPFS of the other patient was 3.9m. Among NSCLC patients who were newly diagnosed with BM after targeted therapy, 8 patients had achieved intracranial progression and 5 patients had reached OS. The median iPFS was 6.13m (95%CI:0.247-1.751) and the mOS was 13.8m (95%CI:0.3660-3.634). Common adverse effects include dry skin, fatigue, dizziness, headache, anorexia, and grade I myelosuppression and no serious adverse events (SAEs); MMSE and FACT-Br scores were no significant differences at baseline and follow-up. Conclusions: In stage IV brain metastatic NSCLC with driver gene mutation, targeted therapy combined with concurrent radiotherapy for BM is tolerable, and there is no significant impact on the quality of life and cognitive function after radiotherapy. The evaluation of efficacy requires further follow-up. Support:LC2019ZD009,81972853 and 81572279.
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Park, SongWon, MinJee Kim, and Seong-Woo Lim. "Clinical Efficacy of Coptidis Rhizoma for Non-alcoholic Fatty Liver Disease: A Systematic Review." Journal of Korean Medicine 43, no. 4 (December 1, 2022): 89–100. http://dx.doi.org/10.13048/jkm.22048.
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Objectives: The purpose of this systematic review was to evaluate the effects of herbal medicine on Chemo -Radiotherapy-induced oral mucositis.Methods: Electronic databases were used to search for studies published through 10 years until October 2022, and a randomized controlled study was conducted to evaluate efficacy of herbal medicine on chemo-radiotherapy-induced oral mucositis. Study quality was assessed using the Cochran’s risk bias tool.Results: Two-hundred and three articles were initially searched, and 11 studies (head and neck cancer, breast cancer, colorectal cancer, esophageal cancer etc. undergoing radio-chemotherapy were included in analysis. The effect of herbal medicine on chemo-radiotherapy-induced oral mucositis, 9 studies reported that herbal medicine was more effective than the placebo group or conventional treatment. One study reported that the effect of the herbal compound treatment group was similar to that of the conventional herbal medicine, and one study reported that there was no difference in effect between the two herbal medicines and the group without treatment.Conclusion: This study suggests that herbal medicine effectively relieves the symptoms of chemo-radiotherapy -induced oral mucositis. However, there is limited evidence that herbal medicine may relief chemo-radiotherapy -induced oral mucositis, so further investigation is needed.
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Bazak, Jerzy, Witold Korytowski, and Albert W. Girotti. "Bystander Effects of Nitric Oxide in Cellular Models of Anti-Tumor Photodynamic Therapy." Cancers 11, no. 11 (October 28, 2019): 1674. http://dx.doi.org/10.3390/cancers11111674.
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Tumor cells exposed to stress-inducing radiotherapy or chemotherapy can send signals to non- or minimally exposed bystander cells. Bystander effects of ionizing radiation are well established, but little is known about such effects in non-ionizing photodynamic therapy (PDT). Our previous studies revealed that several cancer cell types upregulate inducible nitric oxide synthase (iNOS) and nitric oxide (NO) after a moderate 5-aminolevulinic acid (ALA)-based PDT challenge. The NO signaled for cell resistance to photokilling as well as greater growth, migration and invasion of surviving cells. Based on this work, we hypothesized that diffusible NO produced by PDT-targeted cells in a tumor might elicit pro-growth/migration responses in non-targeted bystander cells. In the present study, we tested this using a novel approach, in which ALA-PDT-targeted human cancer cells on culture dishes (prostate PC3, breast MDA-MB-231, glioma U87, or melanoma BLM) were initially segregated from non-targeted bystanders via impermeable silicone-rimmed rings. Several hours after LED irradiation, rings were removed, and both cell populations analyzed for various post-hν responses. For a moderate and uniform level of targeted cell killing by PDT (~25%), bystander proliferation and migration were both enhanced. Enhancement correlated with iNOS/NO upregulation in surviving targeted cells in the following order: PC3 > MDA-MB-231 > U87 > BLM. If occurring in an actual tumor PDT setting and not suppressed (e.g., by iNOS activity or transcription inhibitors), then such effects could compromise treatment efficacy or even stimulate disease progression if PDT’s anti-tumor potency is not great enough.
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Sundberg, �sa Liljegren, Ylva Almqvist, Anna Orlova, Erik Blomquist, Holger J. Jensen, Lars Gedda, Vladimir Tolmachev, and J�rgen Carlsson. "Combined effect of gefitinib ('Iressa', ZD1839) and targeted radiotherapy with 211 At-EGF." European Journal of Nuclear Medicine and Molecular Imaging 30, no. 10 (October 1, 2003): 1348–56. http://dx.doi.org/10.1007/s00259-003-1308-9.
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Mothersill, Carmel, Andrej Rusin, and Colin Seymour. "Relevance of Non-Targeted Effects for Radiotherapy and Diagnostic Radiology; A Historical and Conceptual Analysis of Key Players." Cancers 11, no. 9 (August 23, 2019): 1236. http://dx.doi.org/10.3390/cancers11091236.
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Non-targeted effects (NTE) such as bystander effects or genomic instability have been known for many years but their significance for radiotherapy or medical diagnostic radiology are far from clear. Central to the issue are reported differences in the response of normal and tumour tissues to signals from directly irradiated cells. This review will discuss possible mechanisms and implications of these different responses and will then discuss possible new therapeutic avenues suggested by the analysis. Finally, the importance of NTE for diagnostic radiology and nuclear medicine which stems from the dominance of NTE in the low-dose region of the dose–response curve will be presented. Areas such as second cancer induction and microenvironment plasticity will be discussed.
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Boateng, Francis, and Wilfred Ngwa. "Delivery of Nanoparticle-Based Radiosensitizers for Radiotherapy Applications." International Journal of Molecular Sciences 21, no. 1 (December 31, 2019): 273. http://dx.doi.org/10.3390/ijms21010273.
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Nanoparticle-based radiosensitization of cancerous cells is evolving as a favorable modality for enhancing radiotherapeutic ratio, and as an effective tool for increasing the outcome of concomitant chemoradiotherapy. Nevertheless, delivery of sufficient concentrations of nanoparticles (NPs) or nanoparticle-based radiosensitizers (NBRs) to the targeted tumor without or with limited systemic side effects on healthy tissues/organs remains a challenge that many investigators continue to explore. With current systemic intravenous delivery of a drug, even targeted nanoparticles with great prospect of reaching targeted distant tumor sites, only a portion of the administered NPs/drug dosage can reach the tumor, despite the enhanced permeability and retention (EPR) effect. The rest of the targeted NPs/drug remain in systemic circulation, resulting in systemic toxicity, which can decrease the general health of patients. However, the dose from ionizing radiation is generally delivered across normal tissues to the tumor cells (especially external beam radiotherapy), which limits dose escalation, making radiotherapy (RT) somewhat unsafe for some diseased sites despite the emerging development in RT equipment and technologies. Since radiation cannot discriminate healthy tissue from diseased tissue, the radiation doses delivered across healthy tissues (even with nanoparticles delivered via systemic administration) are likely to increase injury to normal tissues by accelerating DNA damage, thereby creating free radicals that can result in secondary tumors. As a result, other delivery routes, such as inhalation of nanoparticles (for lung cancers), localized delivery via intratumoral injection, and implants loaded with nanoparticles for local radiosensitization, have been studied. Herein, we review the current NP delivery techniques; precise systemic delivery (injection/infusion and inhalation), and localized delivery (intratumoral injection and local implants) of NBRs/NPs. The current challenges, opportunities, and future prospects for delivery of nanoparticle-based radiosensitizers are also discussed.
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Peng, Chanjuan, Yong Wu, Yang Yang, Ningning Li, Xi Chen, Linhui Gu, Dong Xu, and Chen Yang. "Using ultrasound-targeted microbubble destruction to enhance radiotherapy of glioblastoma." Journal of Cancer Research and Clinical Oncology 147, no. 5 (February 6, 2021): 1355–63. http://dx.doi.org/10.1007/s00432-021-03542-5.
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Abstract Objective To investigate the efficacy and mechanism of ultrasound-targeted microbubble destruction (UTMD) combined with radiotherapy (XRT) on glioblastoma. Methods The enhanced radiosensitization by UTMD was assessed through colony formation and cell apoptosis in Human glioblastoma cells (U87MG). Subcutaneous transplantation tumors in 24 nude mice implanted with U87MG cells were randomly assigned to 4 different treatment groups (Control, UTMD, XRT, and UTMD + XRT) based on tumor sizes (100–300 mm3). Tumor growth was observed for 10 days after treatment, and then histopathology stains (HE, CD34, and γH2AX) were applied to the tumor samples. A TUNEL staining experiment was applied to detect the apoptosis rate of mice tumor samples. Meanwhile, tissue proteins were extracted from animal specimens, and the expressions of dsDNA break repair-related proteins from animal specimens were examined by the western blot. Results When the radiotherapy dose was 4 Gy, the colony formation rate of U87MG cells in the UTMD + XRT group was 32 ± 8%, lower than the XRT group (54 ± 14%, p < 0.01). The early apoptotic rate of the UTMD + XRT group was 21.1 ± 3% at 48 h, higher than that of the XRT group (15.2 ± 4%). The tumor growth curve indicated that the tumor growth was inhibited in the UTMD + XRT group compared with other groups during 10 days of observation. In TUNEL experiment, the apoptotic cells of the UTMD + XRT group were higher than that of the XRT group (p < 0.05). The UTMD + XRT group had the lowest MVD value, but was not significantly different from other groups (p > 0.05). In addition, γH2AX increased due to the addition of UTMD to radiotherapy compared to XRT in immunohistochemistry (p < 0.05). Conclusions Our study clearly demonstrated the enhanced destructive effect of UTMD combined with 4 Gy radiotherapy on glioblastoma. This could be partly achieved by the increased ability of DNA damage of tumor cells.
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Pan, Wei, Shaohua Gong, Jianbo Wang, Longhai Yu, Yuanyuan Chen, Na Li, and Bo Tang. "A nuclear-targeted titanium dioxide radiosensitizer for cell cycle regulation and enhanced radiotherapy." Chemical Communications 55, no. 56 (2019): 8182–85. http://dx.doi.org/10.1039/c9cc01651a.
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Mortezaee, Keywan, Masoud Najafi, Bagher Farhood, Amirhossein Ahmadi, Dheyauldeen Shabeeb, and Ahmed E. Musa. "Resveratrol as an Adjuvant for Normal Tissues Protection and Tumor Sensitization." Current Cancer Drug Targets 20, no. 2 (February 11, 2020): 130–45. http://dx.doi.org/10.2174/1568009619666191019143539.
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Cancer is one of the most complicated diseases in present-day medical science. Yearly, several studies suggest various strategies for preventing carcinogenesis. Furthermore, experiments for the treatment of cancer with low side effects are ongoing. Chemotherapy, targeted therapy, radiotherapy and immunotherapy are the most common non-invasive strategies for cancer treatment. One of the most challenging issues encountered with these modalities is low effectiveness, as well as normal tissue toxicity for chemo-radiation therapy. The use of some agents as adjuvants has been suggested to improve tumor responses and also alleviate normal tissue toxicity. Resveratrol, a natural flavonoid, has attracted a lot of attention for the management of both tumor and normal tissue responses to various modalities of cancer therapy. As an antioxidant and anti-inflammatory agent, in vitro and in vivo studies show that it is able to mitigate chemo-radiation toxicity in normal tissues. However, clinical studies to confirm the usage of resveratrol as a chemo-radioprotector are lacking. In addition, it can sensitize various types of cancer cells to both chemotherapy drugs and radiation. In recent years, some clinical studies suggested that resveratrol may have an effect on inducing cancer cell killing. Yet, clinical translation of resveratrol has not yielded desirable results for the combination of resveratrol with radiotherapy, targeted therapy or immunotherapy. In this paper, we review the potential role of resveratrol for preserving normal tissues and sensitization of cancer cells in combination with different cancer treatment modalities.
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Askar, Mostafa A., Heba AS El-Nashar, Mahmood A. Al-Azzawi, Sahar S. Abdel Rahman, and Omama E. Elshawi. "Synergistic Effect of Quercetin Magnetite Nanoparticles and Targeted Radiotherapy in Treatment of Breast Cancer." Breast Cancer: Basic and Clinical Research 16 (January 2022): 117822342210867. http://dx.doi.org/10.1177/11782234221086728.
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Quercetin is a potent cancer therapeutic agent present in fruits and vegetables. The pharmaceutical uses of quercetin are limited due to many problems associated with low solubility, bioavailability, permeability, and instability. In addition, the high doses of quercetin show toxic effects in clinical and experimental studies. Therefore, a new strategy is warranted to overcome these problems without the use of toxic doses. The iron oxide nanoparticles can be used as a drug delivery system. This study aimed to prepare quercetin-conjugated magnetite nanoparticles (QMNPs) using biological simple nanoprecipitation and mediated by fungus Aspergillus oryzae. Also, we initiated in vitro and in vivo studies to determine whether QMNPs might sensitize breast cancer to radiotherapy treatment. The structural, morphological, and magnetic properties of the prepared nanoparticles were studied. The results indicated that QMNPs were spherical in shape and 40 nm in diameter. The in vitro studies showed that the incubation of MCF-7, HePG-2, and A459 cancer cells with QMNPs for 24 h effectively inhibited the growth of cancer cell lines in a concentration-dependent manner with IC50 values of 11, 77.5, and104 nmol/mL, respectively. The combination of QMNPs with irradiation (IR) potently blocked MCF-7 cancer cell proliferation and showed significant changes in the morphology of these cells as observed by bright-field inverted light microscopy. Focusing on the long-term toxicity of QMNPs (20 ml/kg), the assessment of hematological, hepatic, and renal markers indicated no toxic effect. Besides, QMNPs inhibited tumor growth and potently enhanced the lateral radiotherapy treatment in N-methyl-N-nitrosourea (MNU)-induced breast cancer in female white albino rats. These anticancer and radiosensitizing activities were ascribed to cytotoxicity, cell cycle arrest, immunomodulation, and efficiency through induction of apoptosis. In a conclusion, these observations suggest that the QMNPs combined with LRT could act as a potential targeted therapy in breast cancer.
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Tu, Shu-Ju, Pei-Ying Yang, and Ching-Jung Lo. "Effect of External Targeted Radiotherapy on Dosimetry Due to Rapid Clearance of Gold Nanoparticles." Journal of Medical and Biological Engineering 35, no. 5 (September 21, 2015): 634–42. http://dx.doi.org/10.1007/s40846-015-0081-0.
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Czarnecki, A. "Gemcitabine and radiotherapy: Analysis of safe use." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18146. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18146.
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18146 Background: Radiation in combination with chemotherapy offers a significant survival advantage. Preclinical and clinical data indicate that gemcitabine (GEM) is a potent radiosensitizing agent in numerous cancer types used subsequently with radiation given in different doses and techniques. We compared safety/toxic effects of GEM with GEM plus radiation. Methods: Lilly Safety Database was searched for all reports where patients received radiation before, during and after GEM therapy. The string search for ‘radio’, ‘radia’ and a search for MedDRA terms covering possible radiation recall and typical recall phenomena were conducted. Cases were reviewed by a physician and allocated to one of the categories: ‘concurrent’ (radiation and GEM was given at the same time or 7 days apart), and ‘non-concurrent’ (treatment was given more than 7 days apart). Results: In one third of cases who received concurrent treatment the toxicity reported was higher in 3 System Organ Classes (SOC): ‘Injury’, ‘Gastrointestinal disorders’ (GI), and ‘Respiratory’ in comparison to non radiation treated patients: 4.1%, 16%, 14.8% versus 1.4%, 11.2% and 10.5% respectively but toxicity was lower for ‘Blood and lymphatic disorders’ and ‘General disorders’. In cases with ‘non-concurrent’ treatment the results were similar to ‘concurrent’ treatment for the Injury, Respiratory and Blood SOCs but GI toxicity was only 60% of the one seen in non radiation treated patients. In patients with reported radiation recall the most frequent were skin reactions, pneumonitis and myositis. Radiation injury mainly affected targeted tissue organs exposed to direct radiation e.g eosophagitis and pneumonitis for chest irradiation, GI effects for abdominal irradiation. In Non-concurrent administration no correlation between GEM dose and toxicity could be established. In Concurrent cases, treatment dose and technique of radiation, target tissue and volume were factors together with dose and frequency of GEM administration. Conclusions: Review of adverse drug reactions for GEM and radiation treatment reported from estimated GEM exposure of nearly 1.1 million patients suggests that any increase in GEM toxicity in non- concurrent combination regimen other than radiation recall is due to typical radiation toxicity and mainly affects directly irradiated tissues. No significant financial relationships to disclose.
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Haussmann, Jan, Wilfried Budach, Stefanie Corradini, David Krug, Balint Tamaskovics, Edwin Bölke, Freddy-Joel Djiepmo-Njanang, Ioannis Simiantonakis, Kai Kammers, and Christiane Matuschek. "No Difference in Overall Survival and Non-Breast Cancer Deaths after Partial Breast Radiotherapy Compared to Whole Breast Radiotherapy—A Meta-Analysis of Randomized Trials." Cancers 12, no. 8 (August 17, 2020): 2309. http://dx.doi.org/10.3390/cancers12082309.
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Purpose/objective: Adjuvant radiotherapy after breast conserving surgery is the standard approach in early stage breast cancer. However, the extent of breast tissue that has to be targeted with radiation has not been determined yet. Traditionally, the whole breast was covered by two opposing tangential beams. Several randomized trials have tested partial breast irradiation (PBI) compared to whole breast irradiation (WBI) using different radiation techniques. There is evidence from randomized trials that PBI might result in lower mortality rates compared to WBI. We aimed to reassess this question using current data from randomized trials. Material/methods: We performed a systematic literature review searching for randomized trials comparing WBI and PBI in early stage breast cancer with publication dates after 2009. The meta-analysis was performed using the published event rates and the effect sizes for overall survival (OS), breast cancer-specific survival (BCSS), and non-breast cancer death (NBCD) as investigated endpoints. Analysis of subgroups using different radiation techniques was intended. We used hazard ratios (HR) and risk differences (RD) to estimate pooled effect sizes. Statistical analysis was performed using the inverse variance heterogeneity model. Results: We identified eleven studies randomizing between PBI and WBI. We did not find significant differences in OS (n = 14,070; HR = 1.02; CI-95%: 0.89–1.16; p = 0.810, and n = 15,203; RD = −0.001; CI-95%: −0.008–0.006; p = 0.785) and BCSS (n = 15,203; RD = 0.001; CI-95%: −0.002–0.005; p = 0.463). PBI also did not result in a significant decrease of NBCD (n = 15,203; RD = −0.003; CI-95%: −0.010–0.003; p = 0.349). A subgroup analysis by radiation technique also did not point to any detectable differences. Conclusion: In contrast to a previous assessment of mortality, we could not find a detrimental effect of WBI on OS or NBCD. A longer follow-up might be necessary to fully assess the long-term mortality effects of PBI compared to WBI.
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Mulati, Shulipan, Rongsong Jiang, Jinfeng Wang, Yicun Tao, and Weiyi Zhang. "6-Shogaol Exhibits a Promoting Effect with Tax via Binding HSP60 in Non-Small-Cell Lung Cancer." Cells 11, no. 22 (November 19, 2022): 3678. http://dx.doi.org/10.3390/cells11223678.
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Non-small-cell lung cancer (NSCLC) is a prevalent malignant tumor with high morbidity and mortality rates worldwide. Although surgical resection, adjuvant radiotherapy/chemotherapy, and targeted molecular therapy are the cornerstones of NSCLC treatment, NSCLC is associated with high recurrence rates and drug resistance. This study analyzed the potential targets and pathways of 6-Shogaol (6-SH) in NSCLC, showing that 6-SH binds to heat-shock 60 kDa protein (HSP60) in A549 cells, induces cell apoptosis, and arrests the cell cycle possibly by disrupting the mitochondrial function. HSP60 was identified as the target of 6-SH and 6-SH-induced HSP60 degradation which was mediated by the proteasome. The binding of 6-SH with HSP60 altered its stability, inhibited the ERK, Stat3, PI3K, Akt, and mTOR signaling pathways, and Tax acted synergistically with 6-SH, indicating that 6-SH could be developed as a potential therapeutic agent for an NSCLC treatment.
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Garelli, Elena, Achim Rittmeyer, Paul Martin Putora, Markus Glatzer, Ralf Dressel, and Stefan Andreas. "Abscopal effect in lung cancer: three case reports and a concise review." Immunotherapy 11, no. 17 (December 2019): 1445–61. http://dx.doi.org/10.2217/imt-2019-0105.
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The abscopal effect describes the ability of locally administered radiotherapy to induce systemic antitumor effects. Over the past 40 years, reports on the abscopal effect following conventional radiation have been relatively rare, especially in less immunogenic tumors such as lung cancer. However, with the continued development and use of immunotherapy, reports on the abscopal effect have become increasingly frequent during the last decade. Here, we present three illustrative case reports from our own institution and previous published cases of the abscopal effect in patients with non-small cell lung cancer, treated with immune checkpoint inhibitors and radiotherapy. We also present a concise review of the clinical and experimental literature on the abscopal effect in non-small cell lung cancer.
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Lenarczyk, Marek, Ammar J. Alsheikh, Eric P. Cohen, Dörthe Schaue, Amy Kronenberg, Aron Geurts, Slade Klawikowski, David Mattson, and John E. Baker. "T Cells Contribute to Pathological Responses in the Non-Targeted Rat Heart following Irradiation of the Kidneys." Toxics 10, no. 12 (December 18, 2022): 797. http://dx.doi.org/10.3390/toxics10120797.
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Heart disease is a significant adverse event caused by radiotherapy for some cancers. Identifying the origins of radiogenic heart disease will allow therapies to be developed. Previous studies showed non-targeted effects manifest as fibrosis in the non-irradiated heart after 120 days following targeted X-irradiation of the kidneys with 10 Gy in WAG/RijCmcr rats. To demonstrate the involvement of T cells in driving pathophysiological responses in the out-of-field heart, and to characterize the timing of immune cell engagement, we created and validated a T cell knock downrat on the WAG genetic backgrou nd. Irradiation of the kidneys with 10 Gy of X-rays in wild-type rats resulted in infiltration of T cells, natural killer cells, and macrophages after 120 days, and none of these after 40 days, suggesting immune cell engagement is a late response. The radiation nephropathy and cardiac fibrosis that resulted in these animals after 120 days was significantly decreased in irradiated T cell depleted rats. We conclude that T cells function as an effector cell in communicating signals from the irradiated kidneys which cause pathologic remodeling of non-targeted heart.
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Fukunaga, Hisanori, Kiichi Kaminaga, Eri Hirose, Ritsuko Watanabe, Noriko Usami, Kevin M. Prise, and Akinari Yokoya. "No Intercellular Regulation of the Cell Cycle among Human Cervical Carcinoma HeLa Cells Expressing Fluorescent Ubiquitination-Based Cell-Cycle Indicators in Modulated Radiation Fields." International Journal of Molecular Sciences 22, no. 23 (November 26, 2021): 12785. http://dx.doi.org/10.3390/ijms222312785.
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The non-targeted effects of radiation have been known to induce significant alternations in cell survival. Although the effects might govern the progression of tumor sites following advanced radiotherapy, the impacts on the intercellular control of the cell cycle following radiation exposure with a modified field, remain to be determined. Recently, a fluorescent ubiquitination-based cell-cycle indicator (FUCCI), which can visualize the cell-cycle phases with fluorescence microscopy in real time, was developed for biological cell research. In this study, we investigated the non-targeted effects on the regulation of the cell cycle of human cervical carcinoma (HeLa) cells with imperfect p53 function that express the FUCCI (HeLa–FUCCI cells). The possible effects on the cell-cycle phases via soluble factors were analyzed following exposure to different field configurations, which were delivered using a 150 kVp X-ray irradiator. In addition, using synchrotron-generated, 5.35 keV monochromatic X-ray microbeams, high-precision 200 μm-slit microbeam irradiation was performed to investigate the possible impacts on the cell-cycle phases via cell–cell contacts. Collectively, we could not detect the intercellular regulation of the cell cycle in HeLa–FUCCI cells, which suggested that the unregulated cell growth was a malignant tumor. Our findings indicated that there was no significant intercellular control system of the cell cycle in malignant tumors during or after radiotherapy, highlighting the differences between normal tissue and tumor characteristics.
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Protopapa, Maria, Vassilis Kouloulias, Styliani Nikoloudi, Christos Papadimitriou, Giannis Gogalis, and Anna Zygogianni. "From Whole-Brain Radiotherapy to Immunotherapy: A Multidisciplinary Approach for Patients with Brain Metastases from NSCLC." Journal of Oncology 2019 (February 3, 2019): 1–12. http://dx.doi.org/10.1155/2019/3267409.
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Non-small cell lung cancer patients with brain metastases have a multitude of treatment options, but there is currently no international and multidisciplinary consensus concerning their optimal treatment. Local therapies have the principal role, especially in symptomatic patients. Advances in surgery and radiation therapy manage considerable local control. Systemic treatments have shown effect in clinical trials and in real life clinical settings; yet, at present, this is restricted to patients with asymptomatic or stable intracranial lesions. Targeted agents can have a benefit only in patients with EGFR mutations or ALK rearrangement. Immunotherapy has shown impressive results in patients with PD-L1 expression in tumor cells. Its effects can be further enhanced by a synergy with radiotherapy, possibly by increasing the percentage of responders. The present review summarizes the need for more effective systemic treatments, so that the increased intracranial control achieved by local treatments can be translated in an increase in overall survival.
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Shibata, Tomohiro, Duo-Yao Cao, Tahir B. Dar, Faizan Ahmed, Shabir A. Bhat, Luciana C. Veiras, Ellen A. Bernstein, et al. "miR766-3p and miR124-3p Dictate Drug Resistance and Clinical Outcome in HNSCC." Cancers 14, no. 21 (October 27, 2022): 5273. http://dx.doi.org/10.3390/cancers14215273.
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Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors. Our study shows that inhibition of miR124-3p and miR766-3p enhances the sensitivity of HNSCC cell lines, CAL27 and FaDu, to 5-fluorouracil and cisplatin (FP) chemotherapy and radiotherapy. In contrast, overexpression of miR766-3p and miR124-3p confers a resistance phenotype in HNSCC cells. The upregulation of miR124-3p and miR766-3p is associated with increased HNSCC cell invasion and migration. In a xenograft mouse model, inhibition of miR124-3p and miR766-3p enhanced the efficacy of chemo-radiotherapy with reduced growth of resistant HNSCC. For the first time, we identified that miR124-3p and miR766-3p attenuate expression of CREBRF and NR3C2, respectively, in HNSCC, which promotes aggressive tumor behavior by inducing the signaling axes CREB3/ATG5 and β-catenin/c-Myc. Since miR124-3p and miR766-3p affect complementary pathways, combined inhibition of these two miRNAs shows an additive effect on sensitizing cancer cells to chemo-radiotherapy. In conclusion, our study demonstrated a novel miR124-3p- and miR766-3p-based biological mechanism governing treatment-resistant HNSCC, which can be targeted to improve clinical outcomes in HNSCC.
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Gupta, Archana A., Supriya Kheur, A. Thirumal Raj, Ravindra V. Badhe, and Ramesh R. Bhonde. "Reviewing the potential use of scaffold-mediated localized chemotherapy in oncology." Forum of Clinical Oncology 11, no. 3 (December 1, 2020): 23–27. http://dx.doi.org/10.2478/fco-2019-0022.
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Abstract Post-surgical recurrence and metastasis remain to be the major concern in oncology. The absence of any therapeutic modality during the interim period between the surgical intervention and initiation of conventional radiotherapy and chemotherapy allows the residual cancer cells to proliferate, culminating in recurrence and/or metastasis. Introducing a therapeutic modality during this interim period could suppress the proliferation of the residual tumor cells. Further, as the detrimental effects of conventional chemotherapy and radiotherapy drastically reduce the patient’s quality of life, use of therapeutic modality with localized effect can reduce the risk of systemic toxicity. Thus, the present manuscript reviews the potential use of scaffold-mediated local chemotherapy in oncology. Its localized effect would prevent systemic toxicity, while the scaffold serves as an ideal vehicle for the sustained targeted delivery of therapeutic agents.
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Jiang, Lijuan, Aiyun Yu, and Meiling Sun. "Clinical application of nano-biomedical composite materials in treatment and nursing." Materials Express 12, no. 1 (January 1, 2022): 143–48. http://dx.doi.org/10.1166/mex.2022.2127.
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Nano-biocomposite materials are widely used in the treatment and nursing of gynecological tumors. Nanobiocomposite materials can be loaded with anti-tumor drugs to achieve the targeted effect of gynecological tumor treatment. In this article, the nano-biomedical composite gold nanostar particles loaded with the anti-tumor drug doxorubicin hydrochloride (DOX) are incubated with ovarian cancer cells and treated simultaneously by radiotherapy and chemotherapy. Studies have found that radiotherapy or chemotherapy alone has a weaker effect on the survival rate of ovarian cancer cells. Suppose an ovarian cancer cell complex loaded with nano-biomedical composite gold nanostar particles loaded with the anti-tumor drug DOX. In that case, the cell survival rate is significantly reduced after radiotherapy and chemotherapy. Nanobiomedical composite gold nanostar particles can play a synergistic role in the radiotherapy and chemotherapy of gynecological ovarian cancer tumors. They can improve the efficiency of ovarian cancer treatment clinically.
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Guogytė, Kamilė, Aista Plieskienė, Olga Sevriukova, Rima Ladygienė, Julius Žiliukas, and Vinsas Janušonis. "Micronuclei And G2 Assays For Assessment Of Chromosomal Radiosensitivity As Assistant Tool In Radiotherapy: Method-Comparison Study." Sveikatos mokslai 26, no. 5 (December 22, 2016): 63–68. http://dx.doi.org/10.5200/sm-hs.2016.073.
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Radiation therapy is widely used for cancer treatment. Medical application of ionizing radiation can cause different responses in human depending on individual radiosensitivity. Therefore, assessment of individual radiosensitivity could be proposed as assistant tool in optimizing radiotherapy. The cytokinesis- block micronucleus and G2 chromosomal radiosensitivity assays were proposed as appropriate methods for assessment of individual radiosensitivity. In current study we carried out a pilot cytokinesis-block micronucleus and G2 chromosomal radiosensitivity assays comparison by evaluating specificity of chromatid breaks yield and micronuclei frequency in peripheral blood lymphocytes as biomarkers of individual radiosensitivity in three cancer patients treated with radiotherapy. Our study revealed positive correlation between higher increase in frequency of micronuclei and chromatid breaks after in vitro irradiation in radiotherapy patients peripheral blood lymphocytes with occurrence of adverse radiation effects in tissue which are not being targeted. G2 assay appeared to be more sensitive than micronuclei assay for assessment of irradiation-induced alterations in individual radiosensitivity during the radiotherapy that could affect development of treatment side effects. Therefore, further investigations involving more radiotherapy patients as well as healthy donors are required to select the most sensitive method and reveal the possible correlation between individual radiosensitivity and adverse effect of radiotherapy.
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Węgierek-Ciuk, Aneta, Anna Lankoff, Halina Lisowska, Piotr Kędzierawski, Pamela Akuwudike, Lovisa Lundholm, and Andrzej Wojcik. "Cisplatin Reduces the Frequencies of Radiotherapy-Induced Micronuclei in Peripheral Blood Lymphocytes of Patients with Gynaecological Cancer: Possible Implications for the Risk of Second Malignant Neoplasms." Cells 10, no. 10 (October 9, 2021): 2709. http://dx.doi.org/10.3390/cells10102709.
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Gynaecologic cancers are common among women and treatment includes surgery, radiotherapy or chemotherapy, where the last two methods induce DNA damage in non-targeted cells like peripheral blood lymphocytes (PBL). Damaged normal cells can transform leading to second malignant neoplasms (SMN) but the level of risk and impact of risk modifiers is not well defined. We investigated how radiotherapy alone or in combination with chemotherapy induce DNA damage in PBL of cervix and endometrial cancer patients during therapy. Blood samples were collected from nine endometrial cancer patients (treatment with radiotherapy + chemotherapy—RC) and nine cervical cancer patients (treatment with radiotherapy alone—R) before radiotherapy, 3 weeks after onset of radiotherapy and at the end of radiotherapy. Half of each blood sample was irradiated ex vivo with 2 Gy of gamma radiation in order to check how therapy influenced the sensitivity of PBL to radiation. Analysed endpoints were micronucleus (MN) frequencies, apoptosis frequencies and cell proliferation index. The results were characterised by strong individual variation, especially the MN frequencies and proliferation index. On average, despite higher total dose and larger fields, therapy alone induced the same level of MN in PBL of RC patients as compared to R. This result was accompanied by a higher level of apoptosis and stronger inhibition of cell proliferation in RC patients. The ex vivo dose induced fewer MN, more apoptosis and more strongly inhibited proliferation of PBL of RC as compared to R patients. These results are interpreted as evidence for a sensitizing effect of chemotherapy on radiation cytotoxicity. The possible implications for the risk of second malignant neoplasms are discussed.
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Qin, Feng, Guodong Chen, Kwan Yu, Miaomiao Yang, Wei Cao, Peizhong Kong, Shengjie Peng, Mingyu Sun, Lili Nie, and Wei Han. "Golgi Phosphoprotein 3 Mediates Radiation-Induced Bystander Effect via ERK/EGR1/TNF-α Signal Axis." Antioxidants 11, no. 11 (November 1, 2022): 2172. http://dx.doi.org/10.3390/antiox11112172.
Full textAbstract:
The radiation-induced bystander effect (RIBE), an important non-targeted effect of radiation, has been proposed to be associated with irradiation-caused secondary cancers and reproductive damage beyond the irradiation-treated area after radiotherapy. However, the mechanisms for RIBE signal(s) regulation and transduction are not well understood. In the present work, we found that a Golgi protein, GOLPH3, was involved in RIBE transduction. Knocking down GOLPH3 in irradiated cells blocked the generation of the RIBE, whereas re-expression of GOLPH3 in knockdown cells rescued the RIBE. Furthermore, TNF-α was identified as an important intercellular signal molecule in the GOLPH3-mediated RIBE. A novel signal axis, GOLPH3/ERK/EGR1, was discovered to modulate the transcription of TNF-α and determine the level of released TNF-α. Our findings provide new insights into the molecular mechanism of the RIBE and a potential target for RIBE modulation.
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Li, Wei Bo, Stefan Stangl, Alexander Klapproth, Maxim Shevtsov, Alicia Hernandez, Melanie A. Kimm, Jan Schuemann, et al. "Application of High-Z Gold Nanoparticles in Targeted Cancer Radiotherapy—Pharmacokinetic Modeling, Monte Carlo Simulation and Radiobiological Effect Modeling." Cancers 13, no. 21 (October 26, 2021): 5370. http://dx.doi.org/10.3390/cancers13215370.
Full textAbstract:
High-Z gold nanoparticles (AuNPs) conjugated to a targeting antibody can help to improve tumor control in radiotherapy while simultaneously minimizing radiotoxicity to adjacent healthy tissue. This paper summarizes the main findings of a joint research program which applied AuNP-conjugates in preclinical modeling of radiotherapy at the Klinikum rechts der Isar, Technical University of Munich and Helmholtz Zentrum München. A pharmacokinetic model of superparamagnetic iron oxide nanoparticles was developed in preparation for a model simulating the uptake and distribution of AuNPs in mice. Multi-scale Monte Carlo simulations were performed on a single AuNP and multiple AuNPs in tumor cells at cellular and molecular levels to determine enhancements in the radiation dose and generation of chemical radicals in close proximity to AuNPs. A biologically based mathematical model was developed to predict the biological response of AuNPs in radiation enhancement. Although simulations of a single AuNP demonstrated a clear dose enhancement, simulations relating to the generation of chemical radicals and the induction of DNA strand breaks induced by multiple AuNPs showed only a minor dose enhancement. The differences in the simulated enhancements at molecular and cellular levels indicate that further investigations are necessary to better understand the impact of the physical, chemical, and biological parameters in preclinical experimental settings prior to a translation of these AuNPs models into targeted cancer radiotherapy.
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Pérez-Romasanta, Luis A., Elisabet González-Del Portillo, Ana Rodríguez-Gutiérrez, and Ángela Matías-Pérez. "Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination." Cancers 13, no. 2 (January 7, 2021): 192. http://dx.doi.org/10.3390/cancers13020192.
Full textAbstract:
Stereotactic body radiotherapy (SBRT) is an emerging ablative modality for hepatocellular carcinoma (HCC). Most patients with HCC have advanced disease at the time of diagnosis, and therefore, are not candidates for definitive-intent therapies such as resection or transplantation. For this reason, various alternative local and regional therapies have been used to prevent disease progression, palliate symptoms, and delay liver failure. Stereotactic body radiation therapy is a non-invasive technique of delivering ablative doses of radiation to tumors while sparing normal or non-tumor hepatic tissue. Incorporation of SBRT in multidisciplinary HCC management is gradual, initially applied when other liver-directed therapies have failed or are contraindicated, and tried in combination with other locoregional or systemic therapies for more unfavorable conditions by more experienced teams. In order to improve SBRT therapeutic ratio, there has been much interest in augmenting the effect of radiation on tumors by combining it with chemotherapy, molecularly targeted therapeutics, nanoparticles, and immunotherapy. This review aims to synthesize available evidence to evaluate the clinical feasibility and efficacy of SBRT for HCC, and to explore novel radio-potentiation concepts by combining SBRT with novel therapeutics. It is expected that those approaches would result in improved therapeutic outcomes, even though many questions remain with regard to the optimal way to assemble treatments. Further trials are needed to evaluate and consolidate these promising therapies for HCC.
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Pérez-Romasanta, Luis A., Elisabet González-Del Portillo, Ana Rodríguez-Gutiérrez, and Ángela Matías-Pérez. "Stereotactic Radiotherapy for Hepatocellular Carcinoma, Radiosensitization Strategies and Radiation-Immunotherapy Combination." Cancers 13, no. 2 (January 7, 2021): 192. http://dx.doi.org/10.3390/cancers13020192.
Full textAbstract:
Stereotactic body radiotherapy (SBRT) is an emerging ablative modality for hepatocellular carcinoma (HCC). Most patients with HCC have advanced disease at the time of diagnosis, and therefore, are not candidates for definitive-intent therapies such as resection or transplantation. For this reason, various alternative local and regional therapies have been used to prevent disease progression, palliate symptoms, and delay liver failure. Stereotactic body radiation therapy is a non-invasive technique of delivering ablative doses of radiation to tumors while sparing normal or non-tumor hepatic tissue. Incorporation of SBRT in multidisciplinary HCC management is gradual, initially applied when other liver-directed therapies have failed or are contraindicated, and tried in combination with other locoregional or systemic therapies for more unfavorable conditions by more experienced teams. In order to improve SBRT therapeutic ratio, there has been much interest in augmenting the effect of radiation on tumors by combining it with chemotherapy, molecularly targeted therapeutics, nanoparticles, and immunotherapy. This review aims to synthesize available evidence to evaluate the clinical feasibility and efficacy of SBRT for HCC, and to explore novel radio-potentiation concepts by combining SBRT with novel therapeutics. It is expected that those approaches would result in improved therapeutic outcomes, even though many questions remain with regard to the optimal way to assemble treatments. Further trials are needed to evaluate and consolidate these promising therapies for HCC.
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Lan, Bin, Siyuan Zeng, Shuman Zhang, Xiaofan Ren, Yuming Xing, Isabella Kutschick, Susanne Pfeffer, et al. "CRISPR-Cas9 Screen Identifies DYRK1A as a Target for Radiotherapy Sensitization in Pancreatic Cancer." Cancers 14, no. 2 (January 10, 2022): 326. http://dx.doi.org/10.3390/cancers14020326.
Full textAbstract:
Although radiation therapy has recently made great advances in cancer treatment, the majority of patients diagnosed with pancreatic cancer (PC) cannot achieve satisfactory outcomes due to intrinsic and acquired radioresistance. Identifying the molecular mechanisms that impair the efficacy of radiotherapy and targeting these pathways are essential to improve the radiation response of PC patients. Our goal is to identify sensitive targets for pancreatic cancer radiotherapy (RT) using the kinome-wide CRISPR-Cas9 loss-of-function screen and enhance the therapeutic effect through the development and application of targeted inhibitors combined with radiotherapy. We transduced pancreatic cancer cells with a protein kinase library; 2D and 3D library cells were irradiated daily with a single dose of up to 2 Gy for 4 weeks for a total of 40 Gy using an X-ray generator. Sufficient DNA was collected for next-generation deep sequencing to identify candidate genes. In this study, we identified several cell cycle checkpoint kinases and DNA damage related kinases in 2D- and 3D-cultivated cells, including DYRK1A, whose loss of function sensitizes cells to radiotherapy. Additionally, we demonstrated that the harmine-targeted suppression of DYRK1A used in conjunction with radiotherapy increases DNA double-strand breaks (DSBs) and impairs homologous repair (HR), resulting in more cancer cell death. Our results support the use of CRISPR-Cas9 screening to identify new therapeutic targets, develop radiosensitizers, and provide novel strategies for overcoming the tolerance of pancreatic cancer to radiotherapy.