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Radiation immune cancer

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https://www.readbyqxmd.com/read/28721684/pharmacokinetics-microscale-distribution-and-dosimetry-of-alpha-emitter-labeled-anti-pd-l1-antibodies-in-an-immune-competent-transgenic-breast-cancer-model
#1
Jessie R Nedrow, Anders Josefsson, Sunju Park, Tom Bäck, Robert F Hobbs, Cory Brayton, Frank Bruchertseifer, Alfred Morgenstern, George Sgouros
BACKGROUND: Studies combining immune checkpoint inhibitors with external beam radiation have shown a therapeutic advantage over each modality alone. The purpose of these works is to evaluate the potential of targeted delivery of high LET radiation to the tumor microenvironment via an immune checkpoint inhibitor. METHODS: The impact of protein concentration on the distribution of (111)In-DTPA-anti-PD-L1-BC, an (111)In-antibody conjugate targeted to PD-L1, was evaluated in an immunocompetent mouse model of breast cancer...
December 2017: EJNMMI Research
https://www.readbyqxmd.com/read/28718696/tumor-induced-disorder-of-iron-metabolism-in-major-organs-a-new-insight-from-chemical-speciation-of-iron
#2
Rujie Chen, Guangcun Chen
Objective To investigate the evolution of iron speciation in major organs of tumor-bearing mice and its role in cancer formation and cancer-associated complications. Methods The concentration and chemical speciation of iron in the spleen, liver, lung, kidney, heart, blood, muscle, and tumor tissue of healthy mice and tumor-bearing mice were studied by synchrotron radiation-based total reflection X-ray fluorescence spectrometry (SR-TXRF) coupled with X-ray absorption spectroscopy (XAS). Results The TXRF and XAS results showed that the iron content, especially the ferritin content, significantly decreased in the blood and spleen but significantly increased in the liver, lung, and muscle of mice after tumor implantation...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28713771/integrating-hyperthermia-into-modern-radiation-oncology-what-evidence-is-necessary
#3
REVIEW
Jan C Peeken, Peter Vaupel, Stephanie E Combs
Hyperthermia (HT) is one of the hot topics that have been discussed over decades. However, it never made its way into primetime. The basic biological rationale of heat to enhance the effect of radiation, chemotherapeutic agents, and immunotherapy is evident. Preclinical work has confirmed this effect. HT may trigger changes in perfusion and oxygenation as well as inhibition of DNA repair mechanisms. Moreover, there is evidence for immune stimulation and the induction of systemic immune responses. Despite the increasing number of solid clinical studies, only few centers have included this adjuvant treatment into their repertoire...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28707537/a-perspective-on-the-impact-of-radiation-therapy-on-the-immune-rheostat
#4
William H McBride, Ekambaram Ganapathy, Mi-Heon Lee, Jean P Nesseler, Christine Nguyen, Dörthe Schaue
The advent and success of immune checkpoint inhibitors (ICIs) in cancer treatment has broadened the spectrum of tumours that might be considered "immunogenic" and susceptible to immunotherapeutic (IT) intervention. Not all cancer types are sensitive, and not all patients with any given type respond. Combination treatment of ICIs with an established cytotoxic modality such as radiation therapy (RT) is a logical step towards improvement. For one, RT alone has been shown to be genuinely immunomodulatory and secondly pre-clinical data generally support combined ICI-RT approaches...
July 14, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/28707199/radiation-induced-inflammatory-cascade-and-its-reverberating-crosstalks-as-potential-cause-of-post-radiotherapy-second-malignancies
#5
REVIEW
Sonia Gandhi, Sudhir Chandna
The disease-free survival following radiotherapy is often limited by the development of second/secondary cancers. This significant impediment to effective cancer treatment implicated even in the modern-day radiotherapy needs to be countered effectively. Critical analysis reveals that besides achieving effective tumor control, radiotherapy elicits certain cellular and systemic inflammatory events in tumor infiltrate, which remain relatively stable and tend to facilitate "in-field" or "out of field" oncogenesis in due course of time...
July 13, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28705005/radiation-therapy-in-the-management-of-pancreatic-adenocarcinoma-review-of-current-evidence-and-future-opportunities
#6
Tyler P Robin, Karyn A Goodman
The role of radiation therapy for pancreatic cancer is rapidly evolving in every stage of this disease. In resectable disease, there is conflicting evidence for adjuvant therapy, but an ongoing randomized cooperative group trial is attempting to define the role of adjuvant chemoradiation with modern systemic therapies and radiation techniques with an emphasis on radiation quality assurance. In borderline resectable pancreatic cancer (BRPC), there is an emerging body of literature demonstrating the success of neoadjuvant stereotactic body radiation therapy (SBRT) and a randomized cooperative group trial is actively accruing...
June 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28702499/metastasis-of-cervical-cancer-to-breast-a-case-report-and-review-of-literature
#7
Ankit Mangla, Nikki Agarwal, Farid Saei Hamedani, Jiaxiang Liu, Shweta Gupta, Michael R Mullane
Metastasis to the breast from an extra-mammary malignancy has been documented in literature, however cervical cancer metastasis to the breast is very rare. Thirty-eight cases of metastatic deposit to the breast from cervical cancer have been reported in literature. Though most patients present with a breast lump, it is very difficult to clinically distinguish a primary breast malignancy from a metastatic deposit. Histopathology of the tissue, aided with immune-histochemical staining pattern provides a definitive diagnosis...
August 2017: Gynecologic Oncology Reports
https://www.readbyqxmd.com/read/28688697/dose-dependent-enhancement-of-t-lymphocyte-priming-and-ctl-lysis-following-ionizing-radiation-in-an-engineered-model-of-oral-cancer
#8
Megan Morisada, Ellen C Moore, Rachel Hodge, Jay Friedman, Harrison A Cash, James W Hodge, James B Mitchell, Clint T Allen
OBJECTIVES: Determine if direct tumor cell cytotoxicity, antigen release, and susceptibility to T-lymphocyte killing following radiation treatment is dose-dependent. MATERIALS AND METHODS: Mouse oral cancer cells were engineered to express full-length ovalbumin as a model antigen. Tumor antigen release with uptake and cross presentation of antigen by antigen presenting cells with subsequent priming and expansion of antigen-specific T-lymphocytes following radiation was modeled in vitro and in vivo...
August 2017: Oral Oncology
https://www.readbyqxmd.com/read/28687760/hypofractionated-stereotactic-radiation-therapy-activates-the-peripheral-immune-response-in-operable-stage-i-non-small-cell-lung-cancer
#9
Ting Zhang, Haifeng Yu, Chao Ni, Tao Zhang, Luying Liu, Qinghua Lv, Zhigang Zhang, Zhen Wang, Dang Wu, Pin Wu, Guodi Chen, Liancong Wang, Qichun Wei, Jian Huang, Xiaojian Wang
It has been reported that in patients with operable stage I non-small cell lung cancer (NSCLC), overall survival (OS) is better in those who undergo hypofractionated stereotactic radiation therapy (HSRT) than in those who undergo surgery. However, the reason that HSRT has a better OS has not been fully explored. Here, we analyzed reconstitution kinetics in immune cells in the peripheral blood of NSCLC patients after HSRT. We found that HSRT increased the frequency of total T cells, especially the proportion of CD8(+) T cells, but decreased the frequency of inhibitory Tregs...
July 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28686531/microenvironment-and-dose-delivery-dependent-response-after-exposure-to-ionizing-radiation-in-human-colorectal-cancer-cell-lines
#10
Vaidotas Stankevicius, Gintautas Vasauskas, Ryte Rynkeviciene, Jonas Venius, Vita Pasukoniene, Eduardas Aleknaviciusa, Kestutis Suziedelisa
A significant body of knowledge about radiobiology is based on studies of single dose cellular irradiation, despite the fact that conventional clinical applications using dose fractionation. In addition, cellular radiation response strongly depends on cell-cell and cell-extracellular matrix (ECM) interactions, which are poorly established in cancer cells grown under standard 2D cell culture conditions. In this study, we investigated the response of human colorectal carcinoma (CRC) DLD1 and HT29 cell lines, bearing distinct p53 mutations, to a single 2 or 10 Gy dose or fractionated 5 × 2 Gy doses of radiation using global transcriptomics analysis...
July 7, 2017: Radiation Research
https://www.readbyqxmd.com/read/28679765/sequential-tracking-of-pd-l1-expression-and-rad50-induction-in-circulating-tumor-and-stromal-cells-of-lung-cancer-patients-undergoing-radiotherapy
#11
Daniel L Adams, Diane K Adams, Jianzhong He, Neda Kalhor, Ming Zhang, Ting Xu, Hui Gao, James M Reuben, Yawei Qiao, Ritsuko Komaki, Zhongxing Liao, Martin J Edelman, Cha-Mei Tang, Steven H Lin
Evidence suggests that PD-L1 can be induced with radiotherapy and may be an immune escape mechanism in cancer. Monitoring this response is limited as repetitive biopsies during therapy is impractical, dangerous and misses tumor stromal cells. Monitoring PD-L1 expression in both circulating tumor cells (CTCs) and circulating stromal cells (CStCs) in blood based biopsies might be a practical alternative for sequential, non-invasive assessment of changes in tumor and stromal cells. <br /><br />Peripheral blood was collected before and after radiotherapy from 41 lung cancer patients, as was primary biopsies...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28674498/nimotuzumab-induces-nk-cell-activation-cytotoxicity-dendritic-cell-maturation-and-expansion-of-egfr-specific-t-cells-in-head-and-neck-cancer-patients
#12
Zaima Mazorra, Anabel Lavastida, Fernando Concha-Benavente, Anet Valdés, Raghvendra M Srivastava, Tatiana M García-Bates, Esperanza Hechavarría, Zuyen González, Amnely González, Martha Lugiollo, Iván Cuevas, Carlos Frómeta, Braulio F Mestre, Maria C Barroso, Tania Crombet, Robert L Ferris
Survival benefit and long-term duration of clinical response have been seen using the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody (mAb) nimotuzumab. Blocking EGFR signaling may not be the only mechanism of action underlying its efficacy. As an IgG1 isotype mAb, nimotuzumab's capacity of killing tumor cells by antibody dependent cellular cytotoxicity (ADCC) and to induce an immune response in cancer patients have not been studied. ADCC-induced by nimotuzumab was determined using a (51)Cr release assay...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28668899/efficacy-of-adoptive-immune-cell-therapy-in-patients-with-advanced-gastric-cancer-a-retrospective-study
#13
Rishu Takimoto, Takashi Kamigaki, Sachiko Okada, Eriko Matsuda, Hiroshi Ibe, Eri Oguma, Keiko Naitoh, Kaori Makita, Shigenori Goto
BACKGROUND: Conventional therapy for advanced gastric cancer (GC) has limited survival benefits. In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy, using in vitro-activated T-lymphocytes with and without dendritic cells (DCs), in combination with standard therapies in terms of the survival of patients with advanced GC. PATIENTS AND METHODS: A total of 242 patients who were diagnosed as having stage-IV GC were enrolled in this study to receive immune-cell therapy with or without standard therapies, such as chemotherapy, surgery, or radiation therapy...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28668860/gastrocutaneous-fistula-in-a-patient-with-locally-recurrent-msi-high-colorectal-cancer-local-complications-arising-from-therapeutic-response-to-immune-checkpoint-blockade
#14
Claire Greene, Eric K Nakakura, Andrew H Ko
Colorectal cancers with high microsatellite instability (MSI-H) have distinct clinical features in terms of their prognosis, recurrence patterns, and sensitivity to immunotherapeutic agents. We present the case of a woman with a left-sided MSI-H colon cancer who had repeated recurrences concentrated exclusively in the left upper quadrant of the abdomen, including gastric involvement. Despite multiple surgical resections, radiation, and several lines of chemotherapy, her disease eventually eroded through the chest wall...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28668117/expression-and-structural-analyses-of-human-dna-polymerase-%C3%AE-polq
#15
Andrew W Malaby, Sara K Martin, Richard D Wood, Sylvie Doublié
DNA polymerase theta (pol θ) is an evolutionarily conserved protein encoded by the POLQ gene in mammalian genomes. Pol θ is the defining enzyme for a pathway of DSB repair termed "alternative end-joining" (altEJ) or "theta-mediated end-joining." This pathway contributes significantly to the radiation resistance of mammalian cells. It also modulates accuracy in repair of breaks that occur at stalled DNA replication forks, during diversification steps of the mammalian immune system, during repair of CRISPR-Cas9, and in many DNA integration events...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28665741/a-rapid-and-systemic-complete-response-to-stereotactic-body-radiation-therapy-and-pembrolizumab-in-a-patient-with-metastatic-renal-cell-carcinoma
#16
Guozhu Xie, Di Gu, Lanfang Zhang, Shijun Chen, Dehua Wu
Stereotactic body radiation therapy (SBRT) of local tumor would induce an abscopal effect that has been observed in several kinds of human cancers; one important mechanism may involve the improved activation of the host immune system. The immune checkpoint inhibitor can overcome immune tolerance and enhance the activation of antitumor T cells. The combined treatment of SBRT and checkpoint inhibitor may represent a new promising therapeutic approach. Herein, we reported a patient with metastatic renal cell carcinoma (RCC) treated with concurrent SBRT and anti-PD-1 antibody, pembrolizumab, by which the patient achieved an amazingly systemic complete response in only 2...
June 30, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28664471/current-management-strategy-for-penile-cancer-and-future-directions
#17
REVIEW
Tanya B Dorff, Leslie K Ballas, Anne K Schuckman
PURPOSE OF REVIEW: The aim of this review is to evaluate the trends in multidisciplinary management of localized penile cancer and systemic therapy for advanced disease in the evolving era of targeted and immune checkpoint therapy. RECENT FINDINGS: Organ preservation (surgical or incorporating radiation) and reconstructive techniques are important considerations for quality of life in penile cancer survivors. Although local recurrence may be higher with organ preservation, salvage therapy appears successful...
August 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28663235/immunotherapy-of-prostate-cancer-facts-and-hopes
#18
Marijo Bilusic, Ravi A Madan, James L Gulley
In the last few years immunotherapy has become an important cancer treatment modality and while the principles of immunotherapy evolved over many decades, the FDA approvals of sipuleucel-T and ipilimumab began a new wave in immuno-oncology. Despite the current enthusiasm, it is unlikely that any of the immunotherapeutics alone can dramatically change prostate cancer outcomes, but combination strategies are more promising and provide a reason for optimism. Several completed and ongoing studies have shown that the combination of cancer vaccines or checkpoint inhibitors with different immunotherapeutic agents, hormonal therapy (enzalutamide), radiation therapy (radium 223), DNA-damaging agents (olaparib), or chemotherapy (docetaxel) can enhance immune responses and induce more dramatic, long-lasting clinical responses without significant toxicity...
June 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28662958/targeting-atr-in-cancer-medicine
#19
REVIEW
Raghav Sundar, Jessica Brown, Alvaro Ingles Russo, Timothy A Yap
DNA damage occurs continually through various intrinsic and extrinsic mechanisms such as ultraviolet radiation, smoking, reactive oxygen species, and errors during replication. The cellular DNA damage response (DDR) comprises signaling networks that regulate a spectrum of processes, including cell cycle progression, which enable DNA repair to occur. Ataxia telangiectasia mutated (ATM) and ataxia telangiectasia mutated and rad3-related (ATR) kinase are 2 key regulators of the DDR cell cycle checkpoints. ATR plays an essential role in the repair of replication-associated DNA damage, while ATM is activated by DNA double-strand breaks...
May 17, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28662869/radiation-and-pd-1-inhibition-favorable-outcomes-after-brain-directed-radiation
#20
Luke R G Pike, Andrew Bang, Patrick Ott, Tracy Balboni, Allison Taylor, Paul Catalano, Bhupendra Rawal, Alexander Spektor, Monica Krishnan, Daniel Cagney, Brian Alexander, Ayal A Aizer, Elizabeth Buchbinder, Mark Awad, Leena Gandhi, F Stephen Hodi, Jonathan D Schoenfeld
BACKGROUND AND PURPOSE: Patients with metastatic melanoma, renal cell carcinoma (RCC) and non-small cell lung cancer (NSCLC) are increasingly treated with immune checkpoint blockade targeting the programed death (PD)-1 receptor, often with palliative radiation therapy. Outcome data are limited in this population. MATERIAL AND METHODS: We retrospectively reviewed consecutive patients with metastatic NSCLC, melanoma, and RCC who received radiation and anti-PD-1 therapy at four centers...
June 26, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
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