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Irradiation or radiotherapy and immune

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https://www.readbyqxmd.com/read/29138841/enhanced-activated-t%C3%A2-cell-subsets-in-prostate-cancer-patients-receiving-iodine-125-low-dose-rate-prostate-brachytherapy
#1
Makoto Kubo, Takefumi Satoh, Hiromichi Ishiyama, Ken-Ichi Tabata, Hideyasu Tsumura, Shoko Komori, Masatsugu Iwamura, Shiro Baba, Kazushige Hayakawa, Toshihiko Kawamura, Fumiya Obata
Radiotherapy (RT) is one of the most important treatments for prostate cancer. Although RT can kill cancer cells through direct and indirect effects of radiation, it occasionally induces an abscopal effect whereby localized radiation treatment is associated with elimination of metastatic cancer at a distance from the irradiated area. Thus, RT may induce an effective antitumor immune response, although the mechanism involved has remained unclear. The present was designed to evaluate this effect of RT in 36 patients with prostate cancer who provided informed consent prior to enrollment in this clinical trial...
November 13, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29119941/targeting-of-inflammation-for-radiation-protection-and-mitigation
#2
Rasoul Yahyapour, Peyman Amini, Saeed Rezapoor, Abolhasan Rezaeyan, Bagher Farhood, Mohsen Cheki, Hengameh Fallah, Masoud Najafi
Inflammation is the response of the immune system that guards the body against several harmful stimuli in normal conditions. However, in response to ionizing radiation that leads to a massive cell death and DNA aberrations, this phenomenon causes various side effects in normal tissues. Inflammation is involved in various side effects such as gastrointestinal toxicity, mucositis, skin reactions, nervous system damage, pneumonitis, fibrosis and so on. Observations have proposed that inflammatory mediators are involved in the toxic effect of ionizing radiation on non-irradiated cells via a phenomenon named bystander effect...
November 8, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/29113972/localized-synchrotron-irradiation-of-mouse-skin-induces-persistent-systemic-genotoxic-and-immune-responses
#3
Jessica Ventura, Pavel N Lobachevsky, Jason S Palazzolo, Helen Forrester, Nicole M Haynes, Alesia Ivashkevich, Andrew W Stevenson, Christopher J Hall, Andreas Ntargaras, Vasilis Kotsaris, Gerasimos Ch Pollakis, Gianna Potsi, Konstantinos Skordylis, Georgia Terzoudi, Ioannis S Pateras, Vassilis G Gorgoulis, Alexandros G Georgakilas, Carl N Sprung, Olga A Martin
The importance of nontargeted (systemic) effects of ionizing radiation is attracting increasing attention. Exploiting synchrotron radiation generated by the Imaging and Medical Beamline at the Australian Synchrotron, we studied radiation-induced nontargeted effects in C57BL/6 mice. Mice were locally irradiated with a synchrotron X-ray broad beam and a multiplanar microbeam radiotherapy beam. To assess the influence of the beam configurations and variations in peak dose and irradiated area in the response of normal tissues outside the irradiated field at 1 and 4 days after irradiation, we monitored oxidatively induced clustered DNA lesions (OCDL), DNA double-strand breaks (DSB), apoptosis, and the local and systemic immune responses...
November 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/29113340/analgecine-enhances-the-anti-tumor-response-of-radiotherapy-by-increasing-apoptosis-and-cell-cycle-arrest-in-non-small-cell-lung-cancer
#4
Xue Chen, Xibing Zhuang, Qi Zhang, Youjun Luo, Sujuan Yuan, Tiankui Qiao
We investigated whether Analgecine treatment enhanced the antitumor response of radiotherapy in non-small cell lung cancer (NSCLC) cells. Lewis lung carcinoma (LLC) xenograft mice treated with Analgecine plus irradiation showed reduced tumor growth and increased survival. Tumor cell apoptosis was enhanced by Analgecine, based on TUNEL assays. It also increased plasma levels of pro-inflammatory cytokines (IL-6, IL-12, and IFN-γ) and decreased anti-inflammatory cytokines (TGFβ and IL-10), suggesting an enhanced immune response...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29108250/local-irradiation-does-not-enhance-the-effect-of-immunostimulatory-adcd40l-gene-therapy-combined-with-low-dose-cyclophosphamide-in-melanoma-patients
#5
Sandra Irenaeus, Aglaia Schiza, Sara M Mangsbo, Jessica Wenthe, Emma Eriksson, Johan Krause, Anders Sundin, Håkan Ahlström, Thomas H Tötterman, Angelica Loskog, Gustav J Ullenhag
Background: AdCD40L is an immunostimulatory gene therapy under evaluation for advanced melanoma, including ocular melanoma. Herein, we present the final data of a Phase I/IIa trial using AdCD40L alone or in combination with low dose cyclophosphamide +/- radiation therapy. Methods: AdCD40L is a replication-deficient adenovirus carrying the gene for CD40 ligand (CD40L). Twenty-four patients with advanced melanoma were enrolled and treated with AdCD40L monotherapy, or combined with cyclophosphamide +/- single fraction radiotherapy...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29100279/radiotherapy-prolongs-the-survival-of-advanced-non-small-cell-lung-cancer-patients-undergone-to-an-immune-modulating-treatment-with-dose-fractioned-cisplatin-and-metronomic-etoposide-and-bevacizumab-mpebev
#6
Pierpaolo Pastina, Valerio Nardone, Cirino Botta, Stefania Croci, Paolo Tini, Giuseppe Battaglia, Veronica Ricci, Maria Grazia Cusi, Claudia Gandolfo, Gabriella Misso, Silvia Zappavigna, Michele Caraglia, Antonio Giordano, Donatella Aldinucci, Pierfrancesco Tassone, Pierosandro Tagliaferri, Luigi Pirtoli, Pierpaolo Correale
Radiotherapy (RT), together with a direct cytolytic effect on tumor tissue, also elicits systemic immunological events, which sometimes result in the regression of distant metastases (abscopal effect). We have shown the safety and anti-tumor activity of a novel metronomic chemotherapy (mCH) regimen with dose-fractioned cisplatin, oral etoposide and bevacizumab, a mAb against the vasculo-endothelial-growth-factor (mPEBev regimen), in metastatic non-small-cell-lung cancer (mNSCLC). This regimen, designed on the results of translational studies, showed immune-modulating effects that could trigger and empower the immunological effects associated with tumor irradiation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29042994/immunological-mechanism-of-low-dose-priming-radiation-resistance-in-walker-256-tumor-model-mice
#7
Li Feng, Ling Qin, Dan Guo, Daping Deng, Feng Lu, Hailiang Li, Narisu Bao, Xiting Yang, Hongyu Ding, Jianguo Li
The aim of the present study was to investigate whether low-dose priming radiation induces antitumor immunity that can be augmented by the modulation of natural killer (NK) cell and cytokine activity using a mouse tumor model. Walker-256 cells were injected into the right flank of male BALB/c mice. At 7 days after inoculation, mice were divided into three groups, including group 1,2,3. In group 1 the mice were without radiation, in group 2 the mice were received 2 Gy radiation only, and in group 3 the mice were radiated with a priming dose of 75 mGy followed by 2 Gy radiation after 24 h...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29027221/abscopal-immunological-effects-of-radiotherapy-narrowing-the-gap-between-clinical-and-preclinical-experiences
#8
REVIEW
Nikko Brix, Anna Tiefenthaller, Heike Anders, Claus Belka, Kirsten Lauber
Radiotherapy-despite being a local therapy that meanwhile is characterized by an impressively high degree of spatial accuracy-can stimulate systemic phenomena which occasionally lead to regression and rejection of non-irradiated, distant tumor lesions. These abscopal effects of local irradiation have been observed in sporadic clinical case reports since the beginning of the 20th century, and extensive preclinical work has contributed to identify systemic anti-tumor immune responses as the underlying driving forces...
November 2017: Immunological Reviews
https://www.readbyqxmd.com/read/28987882/radiation-enhanced-delivery-of-systemically-administered-amphiphilic-cpg-oligodeoxynucleotide
#9
Oliver K Appelbe, Kelly D Moynihan, Amy Flor, Nick Rymut, Darrell J Irvine, Stephen J Kron
Along with vaccines and checkpoint blockade, immune adjuvants may have an important role in tumor immunotherapy. Oligodeoxynucleotides containing unmethylated cytidyl guanosyl dinucleotide motifs (CpG ODN) are TLR9 ligands with attractive immunostimulatory properties, but intratumoral administration has been required to induce an effective anti-tumor immune response. Following on recent studies with radiation-targeted delivery of nanoparticles, we examined enhanced tumor-specific delivery of amphiphile-CpG, an albumin-binding analog of CpG ODN, following systemic administration 3days after tumor irradiation...
October 5, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28970196/stereotactic-radiotherapy-increases-functionally-suppressive-regulatory-t-cells-in-the-tumor-microenvironment
#10
Yuki Muroyama, Thomas R Nirschl, Christina M Kochel, Zoila Lopez-Bujanda, Debebe Theodros, Wendy Mao, Maria A Carrera-Haro, Ali Ghasemzadeh, Ariel E Marciscano, Esteban Velarde, Ada J Tam, Christopher J Thoburn, Muniza Uddin, Alan K Meeker, Robert A Anders, Drew M Pardoll, Charles G Drake
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 RT enhances the suppressive function of Treg in the TME, we selectively irradiated implanted tumors using the small animal radiation research platform (SARRP), which models stereotactic radiotherapy in human patients...
October 2, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28917247/the-optimism-surrounding-stereotactic-body-radiation-therapy-and-immunomodulation
#11
Hannah Tharmalingam, Peter J Hoskin
In recent years, rapidly evolving radiation techniques have enabled the precise delivery of very high doses of radiation to local targets with stereotactic ablative body radiotherapy (SABR). In addition to its direct cytotoxicity, radiation and in particular SABR has powerful immunomodulatory effects resulting in immunogenic cell death and potentiation of the anti-tumour immune response. However, due to the immunosuppressive nature of non-irradiated sites of metastases, radiotherapy alone is seldom sufficient to induce the systemic response required for distant tumour rejection...
September 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28916224/lack-of-differences-in-radiation-induced-immunogenicity-parameters-between-hpv-positive-and-hpv-negative-human-hnscc-cell-lines
#12
Karolin Schneider, Vanesa Bol, Vincent Grégoire
BACKGROUND AND PURPOSE: Clinical studies indicate that patients with HPV/p16-associated head & neck squamous cell carcinoma (HNSCC) represent a subgroup with a better prognosis and improved response to conventional radiotherapy. Involvement of immune-based factors has been hypothesized. In the present study, we investigated radiation-induced differences in release of damage associated molecular patterns (DAMPs), cytokines and activation of dendritic cells (DCs) in HPV-positive and negative HNSCC cancer cell lines...
September 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28912510/the-th1-th17-balance-dictates-the-fibrosis-response-in-murine-radiation-induced-lung-disease
#13
Alexandra Paun, Marie-Eve Bergeron, Christina K Haston
Radiotherapy can result in lung diseases pneumonitis or fibrosis dependent on patient susceptibility. Herein we used inbred and genetically altered mice to investigate whether the tissue adaptive immune response to radiation injury influences the development of radiation-induced lung disease. Six inbred mouse strains were exposed to 18 Gy whole thorax irradiation and upon respiratory distress strains prone to pneumonitis with fibrosis presented an increased pulmonary frequency of Thelper (Th)17 cells which was not evident in strains prone solely to pneumonitis...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28858075/concurrent-radiotherapy-for-patients-with-metastatic-melanoma-and-receiving-anti-programmed-death-1-therapy-a-safe-and-effective-combination
#14
Amélie Aboudaram, Anouchka Modesto, Léonor Chaltiel, Carlos Gomez-Roca, Serge Boulinguez, Vincent Sibaud, Jean-Pierre Delord, Ciprian Chira, Martine Delannes, Elizabeth Moyal, Nicolas Meyer
A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4...
October 2017: Melanoma Research
https://www.readbyqxmd.com/read/28836991/modeling-dna%C3%A2-damage-induced-pneumopathy-in-mice-insight-from-danger-signaling-cascades
#15
REVIEW
Florian Wirsdörfer, Verena Jendrossek
Radiation-induced pneumonitis and fibrosis represent severe and dose-limiting side effects in the radiotherapy of thorax-associated neoplasms leading to decreased quality of life or - as a consequence of treatment with suboptimal radiation doses - to fatal outcomes by local recurrence or metastatic disease. It is assumed that the initial radiation-induced damage to the resident cells triggers a multifaceted damage-signalling cascade in irradiated normal tissues including a multifactorial secretory program. The resulting pro-inflammatory and pro-angiogenic microenvironment triggers a cascade of events that can lead within weeks to a pronounced lung inflammation (pneumonitis) or after months to excessive deposition of extracellular matrix molecules and tissue scarring (pulmonary fibrosis)...
August 24, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28791251/combining-oncolytic-adenovirus-with-radiation-a-paradigm-for-the-future-of-radiosensitization
#16
REVIEW
Sean M O'Cathail, Tzveta D Pokrovska, Timothy S Maughan, Kerry D Fisher, Leonard W Seymour, Maria A Hawkins
Oncolytic viruses and radiotherapy represent two diverse areas of cancer therapy, utilizing quite different treatment modalities and with non-overlapping cytotoxicity profiles. It is, therefore, an intriguing possibility to consider that oncolytic ("cancer-killing") viruses may act as cancer-selective radiosensitizers, enhancing the therapeutic consequences of radiation treatment on tumors while exerting minimal effects on normal tissue. There is a solid mechanistic basis for this potential synergy, with many viruses having developed strategies to inhibit cellular DNA repair pathways in order to protect themselves, during genome replication, from unwanted interference by cell processes that are normally triggered by DNA damage...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28791250/immunotherapy-combined-with-large-fractions-of-radiotherapy-stereotactic-radiosurgery-for-brain-metastases-implications-for-intraoperative-radiotherapy-after-resection
#17
REVIEW
Carsten Herskind, Frederik Wenz, Frank A Giordano
Brain metastases (BM) affect approximately a third of all cancer patients with systemic disease. Treatment options include surgery, whole-brain radiotherapy, or stereotactic radiosurgery (SRS) while chemotherapy has only limited activity. In cases where patients undergo resection before irradiation, intraoperative radiotherapy (IORT) to the tumor bed may be an alternative modality, which would eliminate the repopulation of residual tumor cells between surgery and postoperative radiotherapy. Accumulating evidence has shown that high single doses of ionizing radiation can be highly efficient in eliciting a broad spectrum of local, regional, and systemic tumor-directed immune reactions...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28751442/towards-precision-radiotherapy-for-use-with-immune-checkpoint-blockers
#18
Claire Vanpouille-Box, Silvia C Formenti, Sandra Demaria
The first evidence that radiation therapy (RT) enhances the efficacy of immune checkpoint blockers (ICBs) was obtained a dozen years ago in a mouse model of metastatic carcinoma refractory to anti-CTLA-4 treatment. At the time, ICBs had just entered clinical testing, an endeavor that culminated in 2011 with the approval of the first anti-CTLA-4 antibody for use in metastatic melanoma patients (ipilimumab). Thereafter, some patients progressing on ipilimumab showed systemic responses only upon receiving radiation to one lesion, confirming clinically the pro-immunogenic effects of radiation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28739315/combination-therapy-of-radiotherapy-and-anti-pd-1-pd-l1-treatment-in-non-small-cell-lung-cancer-a-mini-review
#19
REVIEW
Shinkichi Takamori, Gouji Toyokawa, Kazuki Takada, Fumihiro Shoji, Tatsuro Okamoto, Yoshihiko Maehara
Immune checkpoint inhibitors against programmed cell death-1 (PD-1) or programmed cell death-ligand 1 (PD-L1) are a standard pharmacologic therapy for patients with non-small-cell lung cancer (NSCLC). Substantial data have accumulated in recent years showing that radiotherapy combined with immunotherapy is more effective than monotherapy alone. Preclinical studies have shown that PD-L1 expression is upregulated on tumor cells after radiotherapy, resulting in the synergistically enhanced antitumor effect of irradiation and PD-L1 blockade...
July 6, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28714110/poly-vinylpyrollidone-and-selenocysteine-modified-bi2-se3-nanoparticles-enhance-radiotherapy-efficacy-in-tumors-and-promote-radioprotection-in-normal-tissues
#20
Jiangfeng Du, Zhanjun Gu, Liang Yan, Yuan Yong, Xuan Yi, Xiao Zhang, Jing Liu, Renfei Wu, Cuicui Ge, Chunying Chen, Yuliang Zhao
The development of a new generation of nanoscaled radiosensitizers that can not only enhance radiosensitization of tumor tissues, but also increase radioresistance of healthy tissue is highly desirable, but remains a great challenge. Here, this paper reports a new versatile theranostics based on poly(vinylpyrollidone)- and selenocysteine-modified Bi2 Se3 nanoparicles (PVP-Bi2 Se3 @Sec NPs) for simultaneously enhancing radiotherapeutic effects and reducing the side-effects of radiation. The as-prepared nanoparticles exhibit significantly enhanced free-radical generation upon X-ray radiation, and remarkable photothermal effects under 808 nm NIR laser irradiation because of their strong X-ray attenuation ability and high NIR absorption capability...
September 2017: Advanced Materials
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