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irradiation and immune

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https://www.readbyqxmd.com/read/29144754/immunogenic-cell-death-amplified-by-co-localized-adjuvant-delivery-for-cancer-immunotherapy
#1
Yuchen Fan, Rui Kuai, Yao Xu, Lukasz J Ochyl, Darrell J Irvine, James Moon
Despite their potential, conventional whole-cell cancer vaccines prepared by freeze-thawing or irradiation have shown limited therapeutic efficacy in clinical trials. Recent studies have shown that cancer cells treated with certain chemotherapeutics, such as mitoxantrone, can undergo immunogenic cell death (ICD) and initiate anti-tumor immune responses. However, it remains unclear how ICD can be exploited for cancer immunotherapy. Here, we present a new biomaterial-based strategy for converting immunogenically dying tumor cells into a powerful platform for cancer vaccination and demonstrate their immunogenicity in murine models of melanoma and colon carcinoma...
November 16, 2017: Nano Letters
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
#2
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/29137359/granulysin-expressed-in-a-humanized-mouse-model-induces-apoptotic-cell-death-and-suppresses-tumorigenicity
#3
Ya-Wen Hsiao, Tsung-Ching Lai, Yu-Hsiang Lin, Chia-Yi Su, Jih-Jong Lee, Albert Taiching Liao, Yuan-Feng Lin, Shu-Chen Hsieh, Alexander T H Wu, Michael Hsiao
Granulysin (GNLY) is a cytolytic and proinflammatory protein expressed in activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. Conventional mouse models cannot adequately address the triggering mechanism and immunopathological pathways in GNLY-associated diseases due to lack of the GNLY gene in the mouse genome. Therefore, we generated a humanized immune system (HIS) mouse model by transplanting human umbilical cord blood mononuclear cells into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl) /SzJ (NSG) mice after sublethally irradiation...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29131032/anti-psoriasis-effects-and-mechanisms-of-%C3%AE-8-quinolinoxy-zinc-phthalocyanine-mediated-photodynamic-therapy
#4
Han-Qing Liu, Ying-Ming Wang, Wan-Fang Li, Chao Li, Zhi-Huan Jiang, Jie Bao, Jin-Feng Wei, Hong-Tao Jin, Ai-Ping Wang
BACKGROUND/AIMS: The aim of this study was to determine the anti-psoriasis effects of α-(8-quinolinoxy) zinc phthalocyanine (ZnPc-F7)-mediated photodynamic therapy (PDT) and to reveal its mechanisms. METHODS: HaCaT cells were used to observe the influence of ZnPc-F7-PDT on cell proliferation in vitro. The in vivo anti-psoriasis effects of ZnPc-F7-PDT were evaluated using a mouse vagina model, a propranolol-induced cavy psoriasis model and an imiquimod (IMQ)-induced nude mouse psoriasis model...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29127106/a-melanin-mediated-cancer-immunotherapy-patch
#5
Yanqi Ye, Chao Wang, Xudong Zhang, Quanyin Hu, Yuqi Zhang, Qi Liu, Di Wen, Joshua Milligan, Adriano Bellotti, Leaf Huang, Gianpietro Dotti, Zhen Gu
Melanin is capable of transforming 99.9% of the absorbed sunlight energy into heat, reducing the risk of skin cancer. We here develop a melanin-mediated cancer immunotherapy strategy through a transdermal microneedle patch. B16F10 whole tumor lysate containing melanin is loaded into polymeric microneedles that allow sustained release of the lysate upon insertion into the skin. In combination with the near-infrared light irradiation, melanin in the patch mediates the generation of heat, which further promotes tumor-antigen uptake by dendritic cells, and leads to enhanced antitumor vaccination...
November 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/29124710/ultraviolet-irradiation-of-blood-the-cure-that-time-forgot
#6
Michael R Hamblin
Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However with the development of antibiotics, UBI use declined and it has now been called "the cure that time forgot". Later studies were mostly performed by Russian workers and in other Eastern countries and the modern view in Western countries is that UBI remains highly controversial...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29121114/cd4-levels-control-the-odds-of-induction-of-humoral-immune-responses-to-tracer-doses-of-therapeutic-antibodies
#7
Sharat Srinivasula, Erin Gabriel, Insook Kim, Paula DeGrange, Alexis St Claire, Candace Mallow, Robert E Donahue, Chang Paik, H C Lane, Michele Di Mascio
Rapidly increasing number of therapeutic antibodies are being repurposed to imaging probes for noninvasive diagnosis, as well as monitoring during treatment or disease recurrence. Though antibody-based imaging involves tracer doses (~3 log lower than therapeutic doses), and immune responses are severely reduced in patients with impaired immunity, formation of anti-tracer antibodies (ATA) has been observed hampering further diagnostic monitoring. Here, we explored the potential to develop humoral responses to intravenously administered tracer dose of a monoclonal antibody F(ab΄)2 fragment, and associated with host related immune measures in 49 rhesus macaques categorized into healthy (uninfected controls), SIV-progressors, SIV non-progressors, or total body irradiated (TBI)...
2017: PloS One
https://www.readbyqxmd.com/read/29119941/targeting-of-inflammation-for-radiation-protection-and-mitigation
#8
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/29115465/trichosanthes%C3%A2-kirilowii-extract-enhances-repair-of-uvb-radiation%C3%A2-induced-dna-damage-by-regulating-bmal1-and-mir%C3%A2-142%C3%A2-3p-in-human-keratinocytes
#9
Ji-Hye Joo, In-Kee Hong, Nam Kyoung Kim, Eunmi Choi
Ultraviolet B (UVB) radiation induces DNA damage, oxidative stress and inflammation, and suppresses the immune system in the skin, which collectively contribute to skin aging and carcinogenesis. The DNA damage response, including DNA repair, can be regulated by the circadian clock and microRNA (miRNA) expression. The aim of the present study was to evaluate the reparative action of Trichosanthes kirilowii extract (TKE) against UVB irradiation‑induced DNA damage in human keratinocytes. TKE demonstrated low cytotoxicity in normal HaCaT keratinocytes at low doses (up to 100 µg/ml)...
October 31, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115209/exploring-the-use-of-ingenol-mebutate-to-prevent-non-melanoma-skin-cancer
#10
Andrés Már Erlendsson
Non-melanoma skin cancer is the most frequently occurring cancer in Caucasians today. Incidence rates in Europe have increased steadily since the 1960s and more than tripled over the last 50 years. Despite primary preventative efforts, incidences of non-melanoma skin cancer continue to rise and development of effective chemopreventative strategies is needed. In 2013, ingenol mebutate was approved in Denmark as a new topical drug for field-directed treatment for actinic keratoses. Ingenol mebutate has a dual mechanism of action, causing initial cell death, followed by an immune activation...
November 2017: Danish Medical Journal
https://www.readbyqxmd.com/read/29113972/localized-synchrotron-irradiation-of-mouse-skin-induces-persistent-systemic-genotoxic-and-immune-responses
#11
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
#12
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/29113120/the-sod-mimic-mnte-2-pyp-protects-from-chronic-fibrosis-and-inflammation-in-irradiated-normal-pelvic-tissues
#13
Shashank Shrishrimal, Elizabeth A Kosmacek, Arpita Chatterjee, McDonald J Tyson, Rebecca E Oberley-Deegan
Pelvic radiation for cancer therapy can damage a variety of normal tissues. In this study, we demonstrate that radiation causes acute changes to pelvic fibroblasts such as the transformation to myofibroblasts and the induction of senescence, which persist months after radiation. The addition of the manganese porphyrin, MnTE-2-PyP, resulted in protection of these acute changes in fibroblasts and this protection persisted months following radiation exposure. Specifically, at two months post-radiation, MnTE-2-PyP inhibited the number of α-smooth muscle actin positive fibroblasts induced by radiation and at six months post-radiation, MnTE-2-PyP significantly reduced collagen deposition (fibrosis) in the skin and bladder tissues of irradiated mice...
November 6, 2017: Antioxidants (Basel, Switzerland)
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
#14
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/29107869/surfactant-protein-d-regulates-caspase-8-mediated-cascade-of-the-intrinsic-pathway-of-apoptosis-while-promoting-bleb-formation
#15
Pascal Djiadeu, Nicole Farmakovski, Dhia Azzouz, Lakshmi P Kotra, Neil Sweezey, Nades Palaniyar
Surfactant-associated protein D (SP-D) is a soluble innate immune collectin present on many mucosal surfaces. We recently showed that SP-D suppresses the extrinsic pathway of apoptosis by downregulating caspase-8 activation. However, the effects of SP-D on the intrinsic pathway of apoptosis are not clearly understood. In the intrinsic pathway, cytochrome c is released by mitochondria into the cytoplasm. Oxidation of cytochrome c by cytochrome c oxidase activates the apoptosome and caspase-9 cascade. Both caspase-8- and caspase-9-mediated branches are activated in the intrinsic pathway of apoptosis; however, little is known about the relevance of the caspase-8 pathway in this context...
November 3, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29104735/tracing-and-targeting-cancer-stem-cells-new-venture-for-personalized-molecular-cancer-therapy
#16
REVIEW
Ramin Radpour
Tumors consist of a mixture of heterogeneous cell types. Cancer stem cells (CSCs) are a minor sub-population within the bulk cancer fraction which has been found to reconstitute and propagate the disease and to be frequently resistant to chemotherapy, irradiation, cytotoxic drugs and probably also against immune attack. CSCs are considered as the seeds of tumor recurrence, driving force of tumorigenesis and metastases. This underlines the urgent need for innovative methods to identify and target CSCs. However, the role and existence of CSCs in therapy resistance and cancer recurrence remains a topic of intense debate...
October 26, 2017: World Journal of Stem Cells
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
#17
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/29094483/impact-of-intraoperative-blood-salvage-on-monocyte-subsets-alteration-and-intracellular-tnf-%C3%AE-production
#18
Hagen Bomberg, Thomas Volk, Andreas Biedler, Sven O Schneider
Intraoperative salvaged blood is used to reduce allogeneic blood transfusion in orthopedic surgery patients. However, salvaged blood reinfusion may lead to immune reactions. Salvaged and venous blood from 20 patients undergoing hip arthroplasty was processed. The salvaged samples were mixed with patients' venous blood and incubated in absence or presence of lipopolysaccharide. SAMPLES: Venous: venous patient blood (n=20). Native: mixed salvaged native blood (n=20). Filtered: mixed salvaged leukocyte filtered blood (n=20)...
November 1, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29079696/%C3%AE-%C3%AE-t-cells-are-required-for-the-induction-of-sterile-immunity-during-irradiated-sporozoite-vaccinations
#19
Irfan Zaidi, Hama Diallo, Solomon Conteh, Yvette Robbins, Jacqueline Kolasny, Sachy Orr-Gonzalez, Dariyen Carter, Brandi Butler, Lynn Lambert, Elizabeth Brickley, Robert Morrison, Mahamadou Sissoko, Sara A Healy, B Kim Lee Sim, Ogobara K Doumbo, Stephen L Hoffman, Patrick E Duffy
Whole-sporozoite vaccines confer sterilizing immunity to malaria-naive individuals by unknown mechanisms. In the first PfSPZ Vaccine trial ever in a malaria-endemic population, Vδ2 γδ T cells were significantly elevated and Vγ9/Vδ2 transcripts ranked as the most upregulated in vaccinees who were protected from Plasmodium falciparum infection. In a mouse model, absence of γδ T cells during vaccination impaired protective CD8 T cell responses and ablated sterile protection. γδ T cells were not required for circumsporozoite protein-specific Ab responses, and γδ T cell depletion before infectious challenge did not ablate protection...
October 27, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29079107/dissecting-antigen-processing-and-presentation-routes-in-dermal-vaccination-strategies
#20
Anouk C M Platteel, Sandrine Henri, Dietmar M Zaiss, Alice J A M Sijts
The skin is an attractive site for vaccination due to its accessibility and presence of immune cells surveilling this barrier. However, knowledge of antigen processing and presentation upon dermal vaccination is sparse. In this study we determined antigen processing routes that lead to CD8(+) T cell activation following dermal DNA tattoo immunization, exploiting a model antigen that contains an immunoproteasome-dependent epitope. In agreement with earlier reports, we found that DNA tattoo immunization of wild type (WT) mice triggered vigorous responses to the immunoproteasome-dependent model epitope, whereas gene-deficient mice lacking the immunoproteasome subunits β5i/LMP7 and β2i/MECL1 failed to respond...
October 24, 2017: Vaccine
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