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Radiation immune cancer

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https://www.readbyqxmd.com/read/28806299/the-dynamic-and-transient-immune-microenvironment-in-locally-advanced-esophageal-adenocarcinoma-post-chemoradiation
#1
Ronan J Kelly, Ali H Zaidi, Matthew A Smith, Ashten N Omstead, Juliann E Kosovec, Daisuke Matsui, Samantha A Martin, Christina DiCarlo, E Day Werts, Jan F Silverman, David H Wang, Blair A Jobe
OBJECTIVE: The aim of this study was to assess the impact of chemoradiation on the immune microenvironment to influence and optimally design future neoadjuvant clinical trials. SUMMARY BACKGROUND DATA: Programmed death (PD)-1 inhibitors in metastatic gastroesophageal cancer have demonstrated response rates of approximately 25% in programmed death ligand-1 (PD-L1+) tumors. Unfortunately, the majority of patients do not respond. Therefore, a rationale strategy of combining immunotherapeutic agents with chemoradiation in earlier stage esophageal cancer may prevent metastatic disease in patients...
August 10, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28797029/successful-use-of-equine-anti-thymocyte-globulin-atgam-for-fulminant-myocarditis-secondary-to-nivolumab-therapy
#2
Rebecca Y Tay, Elizabeth Blackley, Catriona McLean, Maggie Moore, Peter Bergin, Sanjeev Gill, Andrew Haydon
BACKGROUND: Immune-mediated myocarditis is an uncommon adverse effect of immune checkpoint inhibition and is associated with a high rate of mortality. METHODS: In this reported case, a 64-year-old woman with right temporo-parietal glioblastoma IDH-WT was treated with nivolumab, temozolomide and radiation therapy on a clinical trial. She developed malignant arrhythmias secondary to histologically confirmed severe immune-mediated myocarditis. She was treated with equine anti-thymocyte globulin (ATGAM) due to development of malignant arrhythmias refractory to high-dose corticosteroids...
August 10, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28795306/lung-cancer-as-a-cardiotoxic-state-a-review
#3
REVIEW
David Pérez-Callejo, María Torrente, María Auxiliadora Brenes, Beatriz Núñez, Mariano Provencio
As the overall survival of patients with lung cancer continues to increase, more cancer survivors are faced with the risk of developing treatment-related cardiovascular toxicities. The increased knowledge of the molecular biology of non-small cell lung cancer has led to new and more personalized treatments. Nevertheless, the usual chemotherapy schemes and radiation therapy induce cardiac toxicities that are frequently underappreciated or go unnoticed. Up to date, the majority of cardiotoxicity studies have been focused in breast cancer, but new treatments in lung cancer patients, such as immune checkpoint-blocking antibodies or tyrosine kinase inhibitors, may also exert these cardiac toxic effects and therefore demand of the close collaboration of oncologists and cardiologists, in order to be addressed...
August 9, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28791251/combining-oncolytic-adenovirus-with-radiation-a-paradigm-for-the-future-of-radiosensitization
#4
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
#5
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/28779867/neurological-complications-of-childhood-cancer
#6
Lauren Weaver, Ayman Samkari
Though the treatment of pediatric cancers has come a long way, acute and chronic effects of cancer are still affecting the life of many children. These effects may be caused not only by the malignancy itself but also by the interventions used for the purpose of treatment. This article focuses primarily on the indirect effects of pediatric cancers and their treatment on the central and peripheral nervous system. Chemotherapy, radiation, and stem cell transplantation cause an immune-compromised state and place the patient at risk of infection, the leading cause of mortality in pediatric cancer...
February 2017: Seminars in Pediatric Neurology
https://www.readbyqxmd.com/read/28777832/endless-research-ii-the-genomic-era-neohippocratic-medicine
#7
EDITORIAL
Philip C Grammaticos, Dimitrios E Antoniou
The great progress of genetics research, during 2015-2017, will certainly influence all medical specialties including nuclear medicine. In nuclear medicine there are still problems to solve as to differentiate between infection, inflammation and cancer etc. Furthermore, in dosimetry and radiation protection there are worldwide problems. It has been reported that (64) Cu-cetuximab immune-PET represented EGFR expression levels in ESCC tumors and that (177) Lu-cetuximab radioimmunotherapy effectively inhibited the tumor growth...
May 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28771183/molecular-interactions-of-autophagy-with-the-immune-system-and-cancer
#8
REVIEW
Yunho Jin, Yunkyung Hong, Chan Young Park, Yonggeun Hong
Autophagy is a highly conserved catabolic mechanism that mediates the degradation of damaged cellular components by inducing their fusion with lysosomes. This process provides cells with an alternative source of energy for the synthesis of new proteins and the maintenance of metabolic homeostasis in stressful environments. Autophagy protects against cancer by mediating both innate and adaptive immune responses. Innate immune receptors and lymphocytes (T and B) are modulated by autophagy, which represent innate and adaptive immune responses, respectively...
August 3, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28766918/the-skin-microbiome-and-immune-system-potential-target-for-chemoprevention
#9
REVIEW
Mohammad Asif Sherwani, Saba Tufail, Anum Fatima Muzaffar, Nabiha Yusuf
There has been increasing interest in understanding the role of the human microbiome in skin diseases. Microbiome studies are being utilized in skin cancer research in numerous ways. Commensal bacteria are being studied as a potential tool to judge the biggest environmental risk of skin cancer, ultraviolet (UV) radiation. Owing to the recognized link of skin microbes in the process of inflammation, there have been theories linking commensal bacteria to skin cancer. Viral metagenomics has also provided insight into virus linked forms of skin cancers...
August 2, 2017: Photodermatology, Photoimmunology & Photomedicine
https://www.readbyqxmd.com/read/28761384/new-pd-l1-inhibitors-in-non-small-cell-lung-cancer-impact-of-atezolizumab
#10
REVIEW
Nagashree Seetharamu, Isabel R Preeshagul, Kevin M Sullivan
The era of immunotherapy has changed the face of how we approach treatment for many oncologic and hematologic malignancies. Lung cancer has been in the forefront of checkpoint inhibition for the past 2 years and has paved the path for other subspecialties. While PD-1 inhibitors nivolumab and pembrolizumab have been approved for non-small cell lung cancer (NSCLC), this review focuses on atezolizumab, its landmark studies, and ongoing trials. Atezolizumab is the first programmed death ligand 1 (PD-L1) inhibitor to receive US Food and Drug Administration (FDA) approval for metastatic NSCLC patients who have progressed on frontline chemotherapy...
2017: Lung Cancer: Targets and Therapy
https://www.readbyqxmd.com/read/28759889/mitotic-progression-following-dna-damage-enables-pattern-recognition-within-micronuclei
#11
Shane M Harding, Joseph L Benci, Jerome Irianto, Dennis E Discher, Andy J Minn, Roger A Greenberg
Inflammatory gene expression following genotoxic cancer therapy is well documented, yet the events underlying its induction remain poorly understood. Inflammatory cytokines modify the tumour microenvironment by recruiting immune cells and are critical for both local and systemic (abscopal) tumour responses to radiotherapy. A poorly understood feature of these responses is the delayed onset (days), in contrast to the acute DNA-damage responses that occur in minutes to hours. Such dichotomous kinetics implicate additional rate-limiting steps that are essential for DNA-damage-induced inflammation...
July 31, 2017: Nature
https://www.readbyqxmd.com/read/28759820/winning-the-battle-but-losing-the-war-mechanisms-and-morphology-of-cancer-therapy-associated-cardiovascular-toxicity
#12
REVIEW
Carolyn Kwak Glass, Richard N Mitchell
In the United States, the lifetime risk of a cancer diagnosis is nearly 40%; in 2016, that represents almost 1.6 million new patients, and despite advances in early diagnosis and treatment, roughly 35% will ultimately die of their malignancy. Fortunately, the number of patients living with a cancer diagnosis also continues to expand, anticipated to be more than 19 million in less than a decade. In calculating the relative risks and benefits of therapy, it is therefore important to consider the morbidity and mortality associated with antitumor therapy itself...
June 30, 2017: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/28756593/serial-changes-in-lymphocyte-subsets-in-patients-with-newly-diagnosed-high-grade-astrocytomas-treated-with-standard-radiation-and-temozolomide
#13
Jian L Campian, Anna F Piotrowski, Xiaobu Ye, Frances T Hakim, Jeremy Rose, Xiao-Yi Yan, Yao Lu, Ronald Gress, Stuart A Grossman
The immune system plays a significant role in cancer prevention and outcome. In high grade astrocytomas (HGA), severe lymphopenia is associated with shortened survival due to tumor progression. This study was performed to quantify serial changes in lymphocyte subsets in HGA following standard radiation (RT) and temozolomide (TMZ). Adults (KPS >60, HIV negative) with newly diagnosed HGA scheduled to receive concurrent RT and TMZ and adjuvant TMZ were eligible. Blood was collected before beginning concurrent RT/TMZ and at weeks 6, 10, 18, and 26, and 3 months after completing adjuvant TMZ...
July 29, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28751442/towards-precision-radiotherapy-for-use-with-immune-checkpoint-blockers
#14
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/28746835/genetic-ataxia-telangiectasia-porcine-model-phenocopies-the-multisystemic-features-of-the-human-disease
#15
Rosanna Beraldi, David K Meyerholz, Alexei Savinov, Attila D Kovács, Jill M Weimer, Jordan A Dykstra, Ryan D Geraets, David A Pearce
Ataxia telangiectasia (AT) is a progressive multisystem autosomal recessive disorder caused by mutations in the AT-mutated (ATM) gene. Early onset AT in children is characterized by cerebellar degeneration, leading to motor impairment. Lung disease and cancer are the two most common causes of death in AT patients. Accelerated thymic involution may contribute to the cancer, and recurrent and/or chronic respiratory infections may be a contributing factor to lung disease in AT. AT patients have fertility issues, are highly sensitive to ionizing radiation and they present oculocutaneous telangiectasia...
July 23, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28741521/hypoxia-inducible-factors-master-regulators-of-cancer-progression
#16
REVIEW
Luana Schito, Gregg L Semenza
Intratumoral hypoxia (reduced O2 availability) is a common finding in human cancer and leads to increased activity of hypoxia-inducible factors (HIFs), which regulate the expression of genes that contribute to angiogenesis, metabolic reprogramming, extracellular matrix remodeling, epithelial-mesenchymal transition, motility, invasion, metastasis, cancer stem cell maintenance, immune evasion, and resistance to chemotherapy and radiation therapy. Conventional anticancer therapies target well-oxygenated and proliferating cancer cells, whereas there are no approved therapies that target hypoxic cancer cells, despite growing clinical and experimental evidence indicating that intratumoral hypoxia is a critical microenvironmental factor driving cancer progression...
December 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28741502/immune-priming-of-the-tumor-microenvironment-by-radiation
#17
REVIEW
Wen Jiang, Charles K Chan, Irving L Weissman, Betty Y S Kim, Stephen M Hahn
Ionizing irradiation can induce a multitude of alterations within the tumor microenvironment. Unlike targeted therapies, radiation delivered to the tumor bed can prompt phenotypic changes in both normal stromal and cancer cells, leading to molecular and physiological alterations within the tumor microenvironment. These environmental modulations directly influence the degree of immunogenicity of the tumor microenvironment and may ultimately affect tumor responsiveness to cancer immunotherapies. Here we review the preclinical evidence for tumor microenvironment-mediated immune suppression and how radiation can modulate immune properties within a tumor...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28740894/postoperative-radiation-therapy-is-associated-with-a-reduced-risk-of-local-recurrence-among-low-risk-merkel-cell-carcinomas-of-the-head-and-neck
#18
Seesha R Takagishi, Tessa E Marx, Christopher Lewis, Erica S Tarabadkar, Ilsa D Juhlin, Astrid Blom, Jayasri G Iyer, Jay J Liao, Yolanda D Tseng, Teresa Fu, Paul Nghiem, Upendra Parvathaneni
PURPOSE: Merkel cell carcinoma (MCC) is a rare and often aggressive skin cancer. Typically, surgery is the primary treatment. Postoperative radiation therapy (PORT) is often recommended to improve local control. It is unclear whether PORT is indicated in patients with favorable Stage IA head and neck (HN) MCC. METHODS AND MATERIALS: We conducted a retrospective analysis of 46 low-risk HN MCC cases treated between 2006 and 2015. Inclusion criteria were defined as a primary tumor size of ≤ 2 cm, negative pathological margins, negative sentinel lymph node biopsy, and no immunosuppression...
October 2016: Advances in Radiation Oncology
https://www.readbyqxmd.com/read/28732383/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#19
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28724760/uv-radiation-activates-toll-like-receptor-9-expression-in-primary-human-keratinocytes-an-event-inhibited-by-human-papillomavirus-type-38-e6-and-e7-oncoproteins
#20
Laura Pacini, Maria Grazia Ceraolo, Assunta Venuti, Giusi Melita, Uzma A Hasan, Rosita Accardi, Massimo Tommasino
Several lines of evidence indicate that cutaneous human papillomavirus (HPV) types belonging to the beta genus of the HPV phylogenetic tree synergise with UV radiation in the development of skin cancer. Accordingly, the E6 and E7 oncoproteins from some beta HPV types are able to deregulate pathways related to immune response and cellular transformation. Toll-like receptor 9 (TLR9), in addition to playing a role in innate immunity, has been shown to be involved in the cellular stress response. Using primary human keratinocytes (PHKs) as experimental models, we have shown that UV irradiation (and other cellular stresses) activates TLR9 expression...
July 19, 2017: Journal of Virology
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