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abscopal breast cancer

Ruijing Liang, Lanlan Liu, Huamei He, Zhikuan Chen, Zhiqun Han, Zhenyu Luo, Zhihao Wu, Mingbing Zheng, Yifan Ma, Lintao Cai
Metastatic triple-negative breast cancer (mTNBC) is an aggressive disease among women worldwide, characterized by high mortality and poor prognosis despite systemic therapy with radiation and chemotherapies. Photodynamic therapy (PDT) is an important strategy to eliminate the primary tumor, however its therapeutic efficacy against metastases and recurrence is still limited. Here, we employed a template method to develop the core-shell gold nanocage@manganese dioxide (AuNC@MnO2 , AM) nanoparticles as tumor microenvironment responsive oxygen producers and near-infrared (NIR)-triggered reactive oxygen species (ROS) generators for oxygen-boosted immunogenic PDT against mTNBC...
May 31, 2018: Biomaterials
Rui Ge, Cangwei Liu, Xue Zhang, Wenjing Wang, Binxi Li, Jie Liu, Yi Liu, Hongchen Sun, Daqi Zhang, Yuchuan Hou, Hao Zhang, Bai Yang
Checkpoint blockade immunotherapy has shown great potential in clinical cancer therapy, but the body's systemic immune must be fully activated and generates a positive tumor-specific immune cell response. In this work, we demonstrate the design of the immune-adjuvant nanodrug carriers on the basis of poly(ethylene glycol)- block-poly(lactic- co-glycolic acid) copolymer-encapsulated Fe3 O4 superparticles (SPs), in which imiquimod (R837), a kind of Toll-like receptor 7 agonist, is loaded. The nanodrug carriers are defined as Fe3 O4 -R837 SPs...
June 7, 2018: ACS Applied Materials & Interfaces
Rong Wang, Tingyang Zhou, Wei Liu, Li Zuo
Cancer cells subjected to ionizing radiation may release signals which can influence nearby non-irradiated cells, termed bystander effects. The transmission of bystander effects among cancer cells involves the activation of inflammatory cytokines, death ligands, and reactive oxygen/nitrogen species. In addition to bystander effects, two other forms of non-target effects (NTEs) have been identified in radiotherapy, as one is called cohort effects and the other is called abscopal effects. Cohort effects represent the phenomenon where irradiated cells can produce signals that reduce the survival of neighboring cells within an irradiated volume...
April 6, 2018: Oncotarget
Ismail Jatoi, John R Benson, Ian Kunkler
Radiotherapy is an integral component of loco-regional therapy for breast cancer. Randomized controlled trials indicate that increasing the extent of extirpative surgery primarily reduces the risk of local recurrences, while the addition of radiotherapy to surgery can also reduce the risk of distant recurrences, thereby lowering breast cancer-specific mortality. This may suggest an "abscopal" effect beyond the immediate zone of loco-regional irradiation that favorably perturbs the natural history of distant micrometastases...
2018: NPJ Breast Cancer
Stephen J Beebe, Brittany P Lassiter, Siqi Guo
Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD)...
March 30, 2018: Cancers
Silvia C Formenti, Percy Lee, Sylvia Adams, Judith D Goldberg, Xiaochun Li, Mike W Xie, Josephine A Ratikan, Carol Felix, Lin Hwang, Kym F Faull, James W Sayre, Sara Hurvitz, John A Glaspy, Begoña Comin-Anduix, Sandra Demaria, Dörthe Schaue, William H McBride
Purpose: This study examined the feasibility, efficacy (abscopal effect), and immune effects of TGFβ blockade during radiotherapy in metastatic breast cancer patients. Experimental Design: Prospective randomized trial comparing two doses of TGFβ blocking antibody fresolimumab. Metastatic breast cancer patients with at least three distinct metastatic sites whose tumor had progressed after at least one line of therapy were randomized to receive 1 or 10 mg/kg of fresolimumab, every 3 weeks for five cycles, with focal radiotherapy to a metastatic site at week 1 (three doses of 7...
February 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Henry Wc Leung, Shyh-Yau Wang, Huang Jin-Jhih, Agnes Lf Chan
The abscopal effect is defined as the clearance of distant tumors after applying localized irradiation to a particular tumor site. It has been proposed that a mechanism for the abscopal effect might be the activation of the immune system, which leads to immunogenic tumor cell death. Here, we describe a woman with advanced breast cancer that received modified ablative radiation therapy that targeted her primary breast tumor. She experienced an apparent regression of metastatic mass in the thoracic spine. This case supported the hypothesis that the abscopal effect might be attributable to an activation of the systemic immune response...
January 2, 2018: Cancer Biology & Therapy
Audrey H Choi, Michael P O'Leary, Shyambabu Chaurasiya, Jianming Lu, Sang-In Kim, Yuman Fong, Nanhai G Chen
BACKGROUND: Triple-negative breast cancer is an aggressive subtype of breast cancer with high recurrence rate and poor prognosis. Here we describe a novel, genetically engineered parapoxvirus that efficiently kills triple-negative breast cancer. METHODS: A novel chimeric parapoxvirus (CF189) was generated via homologous recombination and identified through high-throughput screening. Cytotoxicity was assayed in vitro in 4 triple-negative breast cancer cell lines...
February 2018: Surgery
Zishuo I Hu, Heather L McArthur, Alice Y Ho
The abscopal effect refers to the ability of localized radiation to trigger systemic antitumor effects. Over the past 50 years, reports on the abscopal effect arising from conventional radiation have been relatively rare. However, with the continued development and use of immunotherapy strategies incorporating radiotherapy with targeted immunomodulators and immune checkpoint blockade, the abscopal effect is becoming increasingly relevant in less immunogenic tumors such as breast cancer. Here, we review the mechanism of the abscopal effect, the current preclinical and clinical data, and the application of the abscopal effect in designing clinical trials of immunotherapy combined with radiotherapy in breast cancer...
2017: Current Breast Cancer Reports
Raffaella Marconi, Silvia Strolin, Gianluca Bossi, Lidia Strigari
BACKGROUND: Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR). In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence...
2017: PloS One
Xiaopin Duan, Christina Chan, Nining Guo, Wenbo Han, Ralph R Weichselbaum, Wenbin Lin
An effective, nontoxic, tumor-specific immunotherapy is the ultimate goal in the battle against cancer, especially the metastatic disease. Checkpoint blockade-based immunotherapies have been shown to be extraordinarily effective but benefit only the minority of patients whose tumors have been pre-infiltrated by T cells. Here, we show that Zn-pyrophosphate (ZnP) nanoparticles loaded with the photosensitizer pyrolipid (ZnP@pyro) can kill tumor cells upon irradiation with light directly by inducing apoptosis and/or necrosis and indirectly by disrupting tumor vasculature and increasing tumor immunogenicity...
December 28, 2016: Journal of the American Chemical Society
B Schrand, A P Benaduce, E Gilboa, A S Ishkanian
No abstract text is available yet for this article.
October 1, 2016: International Journal of Radiation Oncology, Biology, Physics
María E Rodriguez-Ruiz, Inmaculada Rodriguez, Saray Garasa, Benigno Barbes, Jose Luis Solorzano, Jose Luis Perez-Gracia, Sara Labiano, Miguel F Sanmamed, Arantza Azpilikueta, Elixabet Bolaños, Alfonso R Sanchez-Paulete, M Angela Aznar, Ana Rouzaut, Kurt A Schalper, Maria Jure-Kunkel, Ignacio Melero
Preclinical and clinical evidence indicate that the proimmune effects of radiotherapy can be synergistically augmented with immunostimulatory mAbs to act both on irradiated tumor lesions and on distant, nonirradiated tumor sites. The combination of radiotherapy with immunostimulatory anti-PD1 and anti-CD137 mAbs was conducive to favorable effects on distant nonirradiated tumor lesions as observed in transplanted MC38 (colorectal cancer), B16OVA (melanoma), and 4T1 (breast cancer) models. The therapeutic activity was crucially performed by CD8 T cells, as found in selective depletion experiments...
October 15, 2016: Cancer Research
Mans Broekgaarden, Milan Kos, Freek A Jurg, Adriaan A van Beek, Thomas M van Gulik, Michal Heger
Although photodynamic therapy (PDT) yields very good outcomes in numerous types of superficial solid cancers, some tumors respond suboptimally to PDT. Novel treatment strategies are therefore needed to enhance the efficacy in these therapy-resistant tumors. One of these strategies is to combine PDT with inhibitors of PDT-induced survival pathways. In this respect, the transcription factor nuclear factor κB (NF-κB) has been identified as a potential pharmacological target, albeit inhibition of NF-κB may concurrently dampen the subsequent anti-tumor immune response required for complete tumor eradication and abscopal effects...
2015: International Journal of Molecular Sciences
Encouse B Golden, Arpit Chhabra, Abraham Chachoua, Sylvia Adams, Martin Donach, Maria Fenton-Kerimian, Kent Friedman, Fabio Ponzo, James S Babb, Judith Goldberg, Sandra Demaria, Silvia C Formenti
BACKGROUND: An abscopal response describes radiotherapy-induced immune-mediated tumour regression at sites distant to the irradiated field. Granulocyte-macrophage colony-stimulating factor is a potent stimulator of dendritic cell maturation. We postulated that the exploitation of the pro-immunogenic effects of radiotherapy with granulocyte-macrophage colony-stimulating factor might result in abscopal responses among patients with metastatic cancer. METHODS: Patients with stable or progressing metastatic solid tumours, on single-agent chemotherapy or hormonal therapy, with at least three distinct measurable sites of disease, were treated with concurrent radiotherapy (35 Gy in ten fractions, over 2 weeks) to one metastatic site and granulocyte-macrophage colony-stimulating factor (125 μg/m(2) subcutaneously injected daily for 2 weeks, starting during the second week of radiotherapy)...
July 2015: Lancet Oncology
Xu-Fang Li, Guo-Ying Zhu, Jian-Ping Wang, Yu Wang
Skeletal complications from radiation therapy have been reported in patients with breast, brain and pelvic cancer, and types of blood cancer. However, it remains to be elucidated whether localized radiotherapy may result in systemic adverse effects on the unirradiated skeleton through an abscopal mechanism. The present study investigated the abscopal effect of radiation on osteoblasts mediated by autologous γ-irradiated cell conditioned medium. Osteoblasts obtained from calvarial bones were incubated with irradiated cell conditioned medium (ICCM) and changes in cell viability, alkaline phosphatase (ALP) activity, mineralization ability, cell apoptosis and the gene expression levels of ALP, osteocalcin (BGP), osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL) and caspase 3 were observed...
July 2015: Molecular Medicine Reports
Hossein Mozdarani
Although radiation carcinogenesis has been shown both experimentally and epidemiologically, the use of ionizing radiation is also one of the major modalities in cancer treatment. Various known cellular and molecular events are involved in carcinogenesis. Apart from the known phenomena, there could be implications for carcinogenesis and cancer prevention due to other biological processes such as the bystander effect, the abscopal effect, intrinsic radiosensitivity and radioadaptation. Bystander effects have consequences for mutation initiated cancer paradigms of radiation carcinogenesis, which provide the mechanistic justification for low-dose risk estimates...
2012: Genes
Sekhara Rao Basavaraju, Clay E Easterly
Radiation therapy while important in the management of several diseases, is implicated in the causation of atherosclerosis and other cardiovascular complications. Cancer and atherosclerosis go through the same stages of initiation, promotion, and complication, beginning with a mutation in a single cell. Clinical observations before the 1960s lead to the belief that the heart is relatively resistant to the doses of radiation used in radiotherapy. Subsequently, it was discovered that the heart is sensitive to radiation and many cardiac structures may be damaged by radiation exposure...
October 2002: Medical Physics
S Mikuriya, S Kamimura, T Kato, H Ooami, T Oda
There are several opinions which denied therapeutic effects of preoperative irradiation, however, we have obtained favorable results by preoperative irradiation for the advanced breast and stomach cancers. Because we treated them by less-fractionated irradiation method with a large dose instead of conventional fractionated one. We adopted this kind of radiation method for the purpose of enhancing the antigenicity of the cancer cells (that means to inhibit the suppression of immune reaction in hosts). Cases of advanced breast cancer were irradiated with 30 Gy at once or 10 Gy at three times a week (total 30 Gy) by betatron electron and we treated advanced stomach cancer with twice a week method (5 Gy or 3 Gy each time, total 40 Gy) by 6 MV X-ray...
October 1983: Gan No Rinsho. Japan Journal of Cancer Clinics
T Okino, N Kan, M Nakanishi, K Satoh, K Mise, S Yamasaki, Y Teramura, T Hori, H Kodama, K Ohgaki
We studied the effect of OK-432 combined AIT in 24 cases of liver metastases of breast cancer. Eleven of the 16 patients (69%) who received intraarterial transfer responded to this therapy. On the other hand, no patients responded to intravenous or intraportal transfer. The minimum cell number for a therapeutic response was 10(9) cells. Four patients had abscopal effects after therapy. The serum CEA level paralleled the therapeutic effects. There were no severe side effects accompanying this therapy. These results indicate that intra-arterial OK-432 combined AIT should be the first choice therapy against liver metastases of breast cancer...
April 1989: Gan to Kagaku Ryoho. Cancer & Chemotherapy
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