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Blood May 2021Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential... (Review)
Review
Plasminogen is an abundant plasma protein that exists in various zymogenic forms. Plasmin, the proteolytically active form of plasminogen, is known for its essential role in fibrinolysis. To date, therapeutic targeting of the fibrinolytic system has been for 2 purposes: to promote plasmin generation for thromboembolic conditions or to stop plasmin to reduce bleeding. However, plasmin and plasminogen serve other important functions, some of which are unrelated to fibrin removal. Indeed, for >40 years, the antifibrinolytic agent tranexamic acid has been administered for its serendipitously discovered skin-whitening properties. Plasmin also plays an important role in the removal of misfolded/aggregated proteins and can trigger other enzymatic cascades, including complement. In addition, plasminogen, via binding to one of its dozen cell surface receptors, can modulate cell behavior and further influence immune and inflammatory processes. Plasminogen administration itself has been reported to improve thrombolysis and to accelerate wound repair. Although many of these more recent findings have been derived from in vitro or animal studies, the use of antifibrinolytic agents to reduce bleeding in humans has revealed additional clinically relevant consequences, particularly in relation to reducing infection risk that is independent of its hemostatic effects. The finding that many viruses harness the host plasminogen to aid infectivity has suggested that antifibrinolytic agents may have antiviral benefits. Here, we review the broadening role of the plasminogen-activating system in physiology and pathophysiology and how manipulation of this system may be harnessed for benefits unrelated to its conventional application in thrombosis and hemostasis.
Topics: Animals; Antifibrinolytic Agents; Brain; Conjunctivitis; Enzyme Activation; Fibrin; Fibrinolysin; Fibrinolysis; Fibrinolytic Agents; Humans; Immunity; Infections; Inflammation; Mice; Plasminogen; Radiodermatitis; Receptors, Cell Surface; Skin Diseases, Genetic; Thrombosis; Tranexamic Acid; Wound Healing; Wounds and Injuries
PubMed: 33735914
DOI: 10.1182/blood.2020008951 -
Radiation Oncology Journal Dec 2023Radiation recall presents as an acute inflammatory reaction triggered by systemic therapy, usually chemotherapy, and is typically limited to an area that was previously...
Radiation recall presents as an acute inflammatory reaction triggered by systemic therapy, usually chemotherapy, and is typically limited to an area that was previously irradiated. Radiation recall reactions are generally self-limiting and most commonly occur in the skin. Many systemic agents have been described to elicit a radiation recall reaction, but the exact pathogenesis is largely unknown. Here, we describe the first reported case of radiation recall dermatitis following cetuximab. While cetuximab is associated with other skin reactions, oncologists should not exclude radiation recall dermatitis as a potential complication of cetuximab infusion in patients with prior radiation, and special attention should be paid to the pattern of skin changes both in terms of location and chronology.
PubMed: 38185934
DOI: 10.3857/roj.2023.00577 -
CMAJ : Canadian Medical Association... Feb 2010
Topics: Administration, Topical; Aged; Anti-Inflammatory Agents; Dermatitis; Female; Humans; Radiodermatitis; Radionuclide Imaging
PubMed: 20026631
DOI: 10.1503/cmaj.090320 -
Breast (Edinburgh, Scotland) Oct 2022and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case... (Observational Study)
Observational Study
BACKGROUND
and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients treated with postoperative radiation therapy following COVID-19 vaccination. In this study we investigated the incidence and severity of radiation recall dermatitis after COVID-19 vaccination in irradiated breast cancer patients.
METHODS
Patients that received at least one COVID-19 vaccination dose during the year after the end of postoperative breast radiation therapy were included in this observational monocentric study. Local symptoms occurring inside the radiation field after vaccination were patient-reported and scored according to the PRO-CTCAE questionnaire. Descriptive data of radiation recall dermatitis incidence and severity, and potential risk factors were evaluated.
RESULTS
A cohort of 361 patients with 756 administered COVID-19 vaccinations was analyzed. Breast symptoms were reported by 7.5% of patients, while radiation recall dermatitis was considered for 5.5%. The incidence of radiation recall dermatitis per single dose of vaccine was 2.6%, with a higher risk for the first dose compared to the second/third (4.4% vs 1%, p = 0.003), especially when administered within the first month after the end of irradiation (12.5% vs 2.2%, p = 0.0004). Local symptoms were generally self-limited and a few cases required anti-inflammatory drugs.
CONCLUSIONS
Radiation recall dermatitis is an uncommon but not rare phenomenon in breast cancer patients that received COVID-19 vaccination within one year after breast irradiation. However, symptoms severity were generally low/mild and reversible. These findings can be useful for patient counseling.
Topics: Breast Neoplasms; COVID-19; COVID-19 Vaccines; Female; Humans; Radiodermatitis; Vaccination
PubMed: 35816893
DOI: 10.1016/j.breast.2022.06.008 -
In Vivo (Athens, Greece) 2022Head and neck cancer is a major malignancy worldwide. The treatment strategy for head and neck cancer usually involves radiotherapy. The main side effect of radiotherapy... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIM
Head and neck cancer is a major malignancy worldwide. The treatment strategy for head and neck cancer usually involves radiotherapy. The main side effect of radiotherapy is radiation dermatitis. Thus, determining the most effective topical regimen for the prevention of radiation dermatitis in head and neck cancer patients is a critical issue.
PATIENTS AND METHODS
PRISMA-NMA guidelines were used in this network meta-analysis. We included only randomized control trials. A random effects model was used. Heterogeneity was evaluated by I and Cochran's Q tests.
RESULTS
We included a total of 1,304 patients in the network meta-analysis. Among them, olive oil was the only effective regimen when compared with usual care (OR=0.18, 95%CI=0.03-0.95). The I value was 56%. The test of heterogeneity yielded a p-value of 0.10.
CONCLUSION
Olive oil was the most effective regimen for the prevention of radiation dermatitis.
Topics: Head and Neck Neoplasms; Humans; Network Meta-Analysis; Olive Oil; Radiodermatitis
PubMed: 35478163
DOI: 10.21873/invivo.12851 -
International Journal of Molecular... Mar 2024An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA... (Review)
Review
An important hallmark of radiation dermatitis is the impairment of the mitotic ability of the stem/progenitor cells in the basal cell layers due to radiation-induced DNA damage, leading to suppressed cell renewal in the epidermis. However, this mechanism alone does not adequately explain the complex pathogenesis of radiation-induced skin injury. In this review, we summarize the latest findings on the complex pathogenesis of radiation dermatitis and correlate these with the clinical features of radiation-induced skin reactions. The current studies show that skin exposure to ionizing radiation induces cellular senescence in the epidermal keratinocytes. As part of their epithelial stress response, these senescent keratinocytes secrete pro-inflammatory mediators, thereby triggering skin inflammation. Keratinocyte-derived cytokines and chemokines modulate intercellular communication with the immune cells, activating skin-resident and recruiting skin-infiltrating immune cells within the epidermis and dermis, thereby orchestrating the inflammatory response to radiation-induced tissue damage. The increased expression of specific chemoattractant chemokines leads to increased recruitment of neutrophils into the irradiated skin, where they release cytotoxic granules that are responsible for the exacerbation of an inflammatory state. Moreover, the importance of IL-17-expressing γδ-T cells to the radiation-induced hyperproliferation of keratinocytes was demonstrated, leading to reactive hyperplasia of the epidermis. Radiation-induced, reactive hyperproliferation of the keratinocytes disturbs the fine-tuned keratinization and cornification processes, leading to structural dysfunction of the epidermal barrier. In summary, in response to ionizing radiation, epidermal keratinocytes have important structural and immunoregulatory barrier functions in the skin, coordinating interacting immune responses to eliminate radiation-induced damage and to initiate the healing process.
Topics: Humans; Epidermis; Keratinocytes; Skin; Radiodermatitis; Dermatitis; Skin Neoplasms; Chemokines
PubMed: 38542294
DOI: 10.3390/ijms25063320 -
Journal of Cellular and Molecular... May 2019Radiation-induced dermatitis is a common and serious side effect after radiotherapy. Current clinical treatments cannot efficiently or fully prevent the occurrence of...
Radiation-induced dermatitis is a common and serious side effect after radiotherapy. Current clinical treatments cannot efficiently or fully prevent the occurrence of post-irradiation dermatitis, which remains a significant clinical problem. Resolving this challenge requires gaining a better understanding of the precise pathophysiology, which in turn requires establishment of a suitable animal model that mimics the clinical condition, and can also be used to investigate the mechanism and explore effective treatment options. In this study, a single dose of 90 Gy irradiation to rats resulted in ulceration, dermal thickening, inflammation, hair follicle loss, and sebaceous glands loss, indicating successful establishment of the model. Few hair follicle cells migrated to form epidermal cells, and both the severity of skin fibrosis and hydroxyproline levels increased with time post-irradiation. Radiation damaged the mitochondria and induced both apoptosis and autophagy of the skin cells. Therefore, irradiation of 90 Gy can be used to successfully establish a rat model of radiation-induced dermatitis. This model will be helpful for developing new treatments and gaining a better understanding of the pathological mechanism of radiation-induced dermatitis. Specifically, our results suggest autophagy regulation as a potentially effective therapeutic target.
Topics: Animals; Apoptosis; Cell Movement; Disease Models, Animal; Hair Follicle; Humans; Neoplasms; Radiation Dosage; Radiation Injuries, Experimental; Radiodermatitis; Radiotherapy; Rats; Skin
PubMed: 30821089
DOI: 10.1111/jcmm.14174 -
Supportive Care in Cancer : Official... Mar 2023Approximately 95% of patients undergoing radiotherapy (RT) experience radiation dermatitis (RD). Evidence has suggested that photobiomodulation therapy (PBMT) can... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Approximately 95% of patients undergoing radiotherapy (RT) experience radiation dermatitis (RD). Evidence has suggested that photobiomodulation therapy (PBMT) can stimulate skin renewal and minimize RD. The aim of the present paper was to investigate the efficacy of PBMT in RD prevention through a comprehensive literature review.
METHODS
A literature search of Ovid MEDLINE, Embase, and Cochrane databases was conducted from 1980 to March 2021 to identify RCT on the use of PBMT for RD prevention. Forest plots were developed using RevMan software to quantitatively compare data between studies.
RESULTS
Five papers were identified: four in breast and one in head and neck cancer patients. Patients receiving PBMT experienced less severe RD than the control groups after 40 Gray (Gy) of RT (grade 3 toxicity: Odds Ratio (OR): 0.57, 95% CI 0.14-2.22, p = 0.42) and at the end of RT (grade 0 + 1 vs. 2 + 3 toxicity: OR: 0.28, 95% CI 0.15-0.53, p < 0.0001). RT interruptions due to RD severity were more frequent in the control group (OR: 0.81, 95% CI 0.10-6.58, p = 0.85).
CONCLUSION
Preventive PBMT may be protective against the development of severe grades of RD and reduce the frequency of RT interruptions. Larger sample sizes and other cancer sites at-risk of RD should be evaluated in future studies to confirm the true efficacy of PBMT, also in preventing the onset of RD and to finalize a standardized protocol to optimize the technique. At present, starting PBMT when RT starts is recommendable, as well as performing 2 to 3 laser sessions weekly.
Topics: Humans; Low-Level Light Therapy; Radiodermatitis; Head and Neck Neoplasms; Skin; Breast
PubMed: 36952036
DOI: 10.1007/s00520-023-07673-y -
Anais Brasileiros de Dermatologia 2023
Topics: Humans; Radiodermatitis; Ibuprofen
PubMed: 36967273
DOI: 10.1016/j.abd.2021.08.017 -
Actas Dermo-sifiliograficas Apr 2017Radiotherapy for cancer is used increasingly. Because skin cells undergo rapid turnover, the ionizing radiation of radiotherapy has collateral effects that are often... (Review)
Review
Radiotherapy for cancer is used increasingly. Because skin cells undergo rapid turnover, the ionizing radiation of radiotherapy has collateral effects that are often expressed in inflammatory reactions. Some of these reactions-radiodermatitis and recall phenomenon, for example-are very familiar to dermatologists. Other, less common radiotherapy-associated skin conditions are often underdiagnosed but must also be recognized.
Topics: Humans; Radiation Dosage; Radiodermatitis
PubMed: 28010872
DOI: 10.1016/j.ad.2016.09.011