Tissue Compliance Meter is a More Reproducible Method of Measuring Radiation-Induced Fibrosis than Late Effects of Normal Tissue-Subjective Objective Management Analytical in Patients Treated with Intracavitary Brachytherapy Accelerated Partial Breast Irr

2013 ◽  
Vol 19 (3) ◽  
pp. 250-258 ◽  
Author(s):  
A. Gabriella Wernicke ◽  
Eleni A. Greenwood ◽  
Shana Coplowitz ◽  
Bhupesh Parashar ◽  
Fridon Kulidzhanov ◽  
...  
Keyword(s):  
Late Effects ◽  
Normal Tissue ◽  
Intracavitary Brachytherapy ◽  
Tissue Compliance ◽  
Radiation Induced ◽  
Reproducible Method ◽  
Objective Management

scholarly journals The CD73/Ado System—A New Player in RT Induced Adverse Late Effects

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1578 ◽  
Author(s):  
Simone de Leve ◽  
Florian Wirsdörfer ◽  
Verena Jendrossek
Keyword(s):  
Tumor Growth ◽  
Cancer Patients ◽  
Late Effects ◽  
Normal Tissue ◽  
Preclinical Models ◽  
Fibrotic Disease ◽  
Normal Tissues ◽  
Therapeutic Gain ◽  
Radiation Induced ◽  
Adenosine Signaling

Radiotherapy (RT) is a central component of standard treatment for many cancer patients. RT alone or in multimodal treatment strategies has a documented contribution to enhanced local control and overall survival of cancer patients, and cancer cure. Clinical RT aims at maximizing tumor control, while minimizing the risk for RT-induced adverse late effects. However, acute and late toxicities of IR in normal tissues are still important biological barriers to successful RT: While curative RT may not be tolerable, sub-optimal tolerable RT doses will lead to fatal outcomes by local recurrence or metastatic disease, even when accepting adverse normal tissue effects that decrease the quality of life of irradiated cancer patients. Technical improvements in treatment planning and the increasing use of particle therapy have allowed for a more accurate delivery of IR to the tumor volume and have thereby helped to improve the safety profile of RT for many solid tumors. With these technical and physical strategies reaching their natural limits, current research for improving the therapeutic gain of RT focuses on innovative biological concepts that either selectively limit the adverse effects of RT in normal tissues without protecting the tumor or specifically increase the radiosensitivity of the tumor tissue without enhancing the risk of normal tissue complications. The biology-based optimization of RT requires the identification of biological factors that are linked to differential radiosensitivity of normal or tumor tissues, and are amenable to therapeutic targeting. Extracellular adenosine is an endogenous mediator critical to the maintenance of homeostasis in various tissues. Adenosine is either released from stressed or injured cells or generated from extracellular adenine nucleotides by the concerted action of the ectoenzymes ectoapyrase (CD39) and 5′ ectonucleotidase (NT5E, CD73) that catabolize ATP to adenosine. Recent work revealed a role of the immunoregulatory CD73/adenosine system in radiation-induced fibrotic disease in normal tissues suggesting a potential use as novel therapeutic target for normal tissue protection. The present review summarizes relevant findings on the pathologic roles of CD73 and adenosine in radiation-induced fibrosis in different organs (lung, skin, gut, and kidney) that have been obtained in preclinical models and proposes a refined model of radiation-induced normal tissue toxicity including the disease-promoting effects of radiation-induced activation of CD73/adenosine signaling in the irradiated tissue environment. However, expression and activity of the CD73/adenosine system in the tumor environment has also been linked to increased tumor growth and tumor immune escape, at least in preclinical models. Therefore, we will discuss the use of pharmacologic inhibition of CD73/adenosine-signaling as a promising strategy for improving the therapeutic gain of RT by targeting both, malignant tumor growth and adverse late effects of RT with a focus on fibrotic disease. The consideration of the therapeutic window is particularly important in view of the increasing use of RT in combination with various molecularly targeted agents and immunotherapy to enhance the tumor radiation response, as such combinations may result in increased or novel toxicities, as well as the increasing number of cancer survivors.

scholarly journals The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 855
Author(s):  
Paola Serrano Martinez ◽  
Lorena Giuranno ◽  
Marc Vooijs ◽  
Robert P. Coppes
Keyword(s):  
Signaling Pathways ◽  
Progenitor Cells ◽  
Tissue Regeneration ◽  
Normal Tissue ◽  
Cellular Response ◽  
Adult Tissue ◽  
Tissue Specific ◽  
Radiation Induced

Radiotherapy is involved in the treatment of many cancers, but damage induced to the surrounding normal tissue is often inevitable. Evidence suggests that the maintenance of homeostasis and regeneration of the normal tissue is driven by specific adult tissue stem/progenitor cells. These tasks involve the input from several signaling pathways. Irradiation also targets these stem/progenitor cells, triggering a cellular response aimed at achieving tissue regeneration. Here we discuss the currently used in vitro and in vivo models and the involved specific tissue stem/progenitor cell signaling pathways to study the response to irradiation. The combination of the use of complex in vitro models that offer high in vivo resemblance and lineage tracing models, which address organ complexity constitute potential tools for the study of the stem/progenitor cellular response post-irradiation. The Notch, Wnt, Hippo, Hedgehog, and autophagy signaling pathways have been found as crucial for driving stem/progenitor radiation-induced tissue regeneration. We review how these signaling pathways drive the response of solid tissue-specific stem/progenitor cells to radiotherapy and the used models to address this.

Radiation-Induced Normal Tissue Injury

2013 ◽  
pp. 726-727
Author(s):  
Ning J. Yue ◽  
Kent Lambert ◽  
Jay E. Reiff ◽  
Anthony E. Dragun ◽  
Ning J. Yue ◽  
...  
Keyword(s):  
Normal Tissue ◽  
Tissue Injury ◽  
Radiation Induced

scholarly journals Neoadjuvant Radiotherapy-Related Wound Morbidity in Soft Tissue Sarcoma: Perspectives for Radioprotective Agents

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2258
Author(s):  
Cameron M. Callaghan ◽  
M. M. Hasibuzzaman ◽  
Samuel N. Rodman ◽  
Jessica E. Goetz ◽  
Kranti A. Mapuskar ◽  
...  
Keyword(s):  
Wound Healing ◽  
Soft Tissue ◽  
Adjuvant Radiotherapy ◽  
Normal Tissue ◽  
Soft Tissue Sarcomas ◽  
Limb Amputation ◽  
Neoadjuvant Radiotherapy ◽  
Normal Tissue Toxicity ◽  
Radiation Induced ◽  
Intensity Radiation

Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patients. Generally, neoadjuvant radiation offers decreased volume and dose of high-intensity radiation to normal tissue and increased chance of achieving negative surgical margins—but also increases wound healing complications when compared to adjuvant radiotherapy. This review elaborates on the current neoadjuvant/adjuvant RT approaches, wound healing complications in STS, and the potential application of novel radioprotective agents to minimize radiation-induced normal tissue toxicity.

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