Radiation-Induced Oral Mucositis.
Ontology highlight
ABSTRACT:
SUBMITTER: Maria OM
PROVIDER: S-EPMC5439125 | biostudies-literature | 2017
REPOSITORIES: biostudies-literature
Publications
Radiation-Induced Oral Mucositis.
Maria Osama Muhammad OM Eliopoulos Nicoletta N Muanza Thierry T
Frontiers in oncology 20170522
Radiation-induced oral mucositis (RIOM) is a major dose-limiting toxicity in head and neck cancer patients. It is a normal tissue injury caused by radiation/radiotherapy (RT), which has marked adverse effects on patient quality of life and cancer therapy continuity. It is a challenge for radiation oncologists since it leads to cancer therapy interruption, poor local tumor control, and changes in dose fractionation. RIOM occurs in 100% of altered fractionation radiotherapy head and neck cancer pa ...[more]
Similar Datasets
Project description:Dynamic shifts in oral microbiota in patients with mucositis during radiotherapy.
| PRJEB15392 | ENA
Project description:PURPOSE:To evaluate if two pharmacological agents, Tempol and D-methionine (D-met), are able to prevent oral mucositis in mice after exposure to ionizing radiation ± cisplatin. METHODS AND MATERIALS:Female C3H mice, ?8 weeks old, were irradiated with five fractionated doses ± cisplatin to induce oral mucositis (lingual ulcers). Just before irradiation and chemotherapy, mice were treated, either alone or in combination, with different doses of Tempol (by intraperitoneal [ip] injection or topically, as an oral gel) and D-met (by gavage). Thereafter, mice were sacrificed and tongues were harvested and stained with a solution of Toluidine Blue. Ulcer size and tongue epithelial thickness were measured. RESULTS:Significant lingual ulcers resulted from 5 × 8 Gy radiation fractions, which were enhanced with cisplatin treatment. D-met provided stereospecific partial protection from lingual ulceration after radiation. Tempol, via both routes of administration, provided nearly complete protection from lingual ulceration. D-met plus a suboptimal ip dose of Tempol also provided complete protection. CONCLUSIONS:Two fairly simple pharmacological treatments were able to markedly reduce chemoradiation-induced oral mucositis in mice. This proof of concept study suggests that Tempol, alone or in combination with D-met, may be a useful and convenient way to prevent the severe oral mucositis that results from head-and-neck cancer therapy.
| S-EPMC3314135 | biostudies-literature
Project description:The generation of a self-resolved radiation-induced oral mucositis (RIOM) mouse model using the highest possibly tolerable single ionizing radiation (RT) dose was needed in order to study RIOM management solutions. We used 10-week-old male BALB/c mice with average weight of 23?g for model production. Mice were treated with an orthovoltage X-ray irradiator to induce the RIOM ulceration at the intermolar eminence of the animal tongue. General anesthesia was injected intraperitoneally for proper animal immobilization during the procedure. Ten days after irradiation, a single RT dose of 10, 15, 18, 20, and 25?Gy generated a RIOM ulcer at the intermolar eminence (posterior upper tongue surface) with mean ulcer floor (posterior epithelium) heights of 190, 150, 25, 10, and 10??m, respectively, compared to 200??m in non-irradiated animals. The mean RIOM ulcer size % of the total epithelialized upper surface of the animal tongue was RT dose dependent. At day 10, the ulcer size % was 2, 5, 27, and 31% for 15, 18, 20, and 25?Gy RT, respectively. The mean relative surface area of the total epithelialized upper surface of the tongue was RT dose dependent, since it was significantly decreased to 97, 95, 88, and 38% with 15, 18, 20, and 25?Gy doses, respectively, at day 10 after RT. Subcutaneous injection of 1?mL of 0.9% saline/6?h for 24?h yielded a 100% survival only with 18?Gy self-resolved RIOM, which had 5.6?±?0.3?days ulcer duration. In conclusion, we have generated a 100% survival self-resolved single-dose RIOM male mouse model with long enough duration for application in RIOM management research. Oral mucositis ulceration was radiation dose dependent. Sufficient hydration of animals after radiation exposure significantly improved their survival.
| S-EPMC4921469 | biostudies-literature
Project description:Opinion statementOral mucositis (OM) causes significant detriment to patient quality of life. Despite advances in RT, chemotherapy, and surgery for HNC which have led to improved local control and survival, management of certain toxicities such as OM have not kept pace. Numerous strategies have emerged with demonstrable benefit in preventing severe OM. However, ones which are not only effective, but practical and affordable to implement are rare. For example, infusion of growth factors or free radical scavengers, and daily treatment of intra-oral sites with lasers are supported by high-quality evidence but have not become widely adopted. It falls to familiarity of the physician with the available preventative measures and ultimately, patient preference in accepting which strategies for OM amelioration are used. In this review, we present a pathophysiological-based review of prevention techniques available for reducing the incidence and duration of severe OM.
| S-EPMC8931694 | biostudies-literature
Project description:Introduction:Oral mucositis, the most common adverse effect of radiotherapy (RT) and/or chemotherapy is observed in almost 97% of patients with head and neck cancer. Although several agents like corticosteroids, lidocaine and vitamins are available for its prevention or management, results are often disappointing. Here we report on the effects of a topically applied, highly purified natural deoxyribonucleic acid from sturgeon gonads on three cases of moderate to severe oral mucositis in patients with head and neck cancer. Case Description:Three patients who had undergone RT and/or chemotherapy received an oral spray containing sodium salt-based natural deoxyribonucleic acid (PDRN) for Grade 3 oral mucositis. Treatment continued for one month after the end of RT. No patient reported any allergic reactions. RT and chemotherapy were not interrupted and opioid therapy was not given to any patient. Pain was relieved about 2-3?days after starting treatment and oral mucositis was reduced to G2 within one week. Conclusions:Outcomes in all 3 cases showed topical use of the sodium salt-based PDRN derived from sturgeon gonads was acceptable and safe when used topically for therapeutic and regenerative purposes.Present results are encouraging and suggest a more in-depth study is warranted on its use in a larger patient cohort with RT-induced oral mucositis.
| S-EPMC7033775 | biostudies-literature
Project description:Radiation-induced oral mucositis (RIOM) is one of the most common side effects of radiotherapy in cancer patients, especially in almost all head and neck cancer patients. It presents as severe pain and ulceration. The development of RIOM is composed of five stages: initiation, primary damage response, signal amplification, ulceration, and healing. However, the key regulators involved in the RIOM pathogenesis remain largely unknown. In this study, we reveal a novel role of miR-200c, a member of the miR-200 family, in modulating RIOM pathogenesis. Using a mouse model mimicking RIOM, we found that the miR-200 family numbers (miR-141, miR-200a, miR-200b, and miR-200c) except miR-429 were significantly induced during the RIOM formation. Besides, in RIOM mice, miR-200c expression level was also increased dramatically in the normal human keratinocytes (NHKs) after irradiation. Knockdown of miR-200c expression with miR-200c-3p-shRNA significantly reduced senescence phenotype and enhanced cell proliferation in NHKs after irradiation. The generation of reactive oxygen species (ROS) and p47 enzyme involved in ROS production was increased after irradiation but both were markedly reduced in NHKs by miR-200c inhibition. Knockdown of miR-200c expression in NHKs increased DNA double-strand break repair after irradiation compared with control NHKs. Furthermore, miR-200c inhibition repressed the production of proinflammatory cytokines (TGF-β, TNF-α, and IL-1α) via inhibiting NF-κB and Smad2 activation in NHKs exposed to IR. Additionally, miR-200c inhibition promoted NHK migration and increased the expression of molecules that regulate epithelial to mesenchymal transition, including Snail, Vimentin, Zeb1, and Bmi-1. These results not only identify the key role of miR-200c in the pathogenesis of RIOM but also provide a novel therapeutic target to treat RIOM.
| S-EPMC6620860 | biostudies-literature
Project description:Radiation-induced oral mucositis is a major adverse event of radiotherapy. Severe oral mucositis may cause unwanted interruption in radiotherapy and reduce long-term survival in cancer patients receiving radiotherapy, but until now, there have been no effective options for preventing radiation-induced oral mucositis. Quercetin is a flavonoid that is widely found in food species and has anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated a new role of quercetin in preventing radiation-induced oral mucositis. Quercetin exerted preventive effects against radiation-induced oral mucositis induced by single-dose (25 Gy) ionizing radiation or fractionated ionizing radiation (8 Gy × 3) in C57BL/6 mice and maintained the proliferation ability of basal epithelial cells. Quercetin pretreatment alleviated reactive oxygen species generation, NF-κB pathway activation, and downstream proinflammatory cytokine production and reduced DNA double-strand breaks and cellular senescence induced by ionizing radiation. Quercetin also upregulated BMI-1 expression in oral epithelial cells and promoted ulcer repair. In addition, quercetin exerted similar radioprotective effects in irradiated primary cultured normal human keratinocytes, reduced reactive oxygen species generation and proinflammatory cytokine release, and promoted DNA double-strand break repair and wound healing by upregulating the expression of BMI-1, which is a polycomb group protein. Thus, quercetin can block multiple pathological processes of radiation-induced oral mucositis by targeting BMI-1 and may be a potential treatment option for preventing radiation-induced oral mucositis.
| S-EPMC8643266 | biostudies-literature
Project description:We report that K5.Smad7 mice, which express a Smad7 transgene under the control of a keratin 5 promoter, were resistant to radiation-induced oral mucositis, a painful oral ulceration. In addition to nuclear factor ?B (NF-?B) activation, which is known to contribute to oral mucositis, we found activated transforming growth factor ? (TGF-?) signaling in cells from this condition. Smad7 dampened both pathways to attenuate inflammation, growth inhibition and apoptosis. Additionally, Smad7 promoted oral epithelial migration to close the wound. Further analyses revealed that TGF-? signaling Smads and their co-repressor C-terminal binding protein 1 (CtBP1) transcriptionally repressed Rac1, and that Smad7 abrogated this repression. Knocking down Rac1 expression in mouse keratinocytes abrogated Smad7-induced migration. Topical application of Smad7 protein conjugated with a cell-permeable Tat tag to oral mucosa showed prophylactic and therapeutic effects on radiation-induced oral mucositis in mice. Thus, we have identified new molecular mechanisms involved in oral mucositis pathogenesis, and our data suggest an alternative therapeutic strategy to block multiple pathological processes in this condition.
| S-EPMC3780964 | biostudies-literature
Project description:PurposeThe present study investigates the impact of systemic application of heparins on the manifestation of radiation-induced oral mucositis in a well-established mouse model.Materials and methodsMale C3H/Neu mice were irradiated with either single-dose or fractionated irradiation protocols with 5 × 3 Gy/week, given over one (days 0-4) or two (days 0-4, 7-11) weeks. All fractionation protocols were concluded by a local test irradiation (day 7/14) using graded doses to generate complete dose-effect curves. Daily doses of unfractionated or low molecular weight heparin (40 or 200 I.U./mouse, respectively) were applied subcutaneously over varying time intervals. The incidence and the time course of mucosal ulceration, corresponding to confluent mucositis in patients (RTOG/EORTC grade 3), were analysed as clinically relevant endpoints.ResultsSystemic application of heparins significantly increased the iso-effective doses for the induction of mucosal ulceration, particularly in combination with fractionated irradiation protocols. Moreover, a tentative prolongation of the latent time and a pronounced reduction of the ulcer duration were observed.ConclusionThese data provide the first evidence for a protective and/or mitigative effect of heparins for radiation-induced oral mucositis. Further studies are ongoing investigating the underlying mechanism.
| S-EPMC6008356 | biostudies-literature
Project description:BackgroundOral mucositis is the most common oral complication of cancer patients receiving radiotherapy and/or chemotherapy, leading to poor quality of life. Limitations of the current interventions on radiation-induced oral mucositis (RIOM) urge the development of novel therapeutics. Here, we evaluated the treatment outcome of probiotic Streptococcus salivarius K12 on RIOM mice, and oral microbiota that is associated with the progress of RIOM was further investigated.MethodsAn experimental RIOM mouse model was established, and S. salivarius K12 was applied to the mouse oral cavity daily. Histological analyses were performed to evaluate the severity of oral mucositis and the treatment outcome of S. salivarius K12. The oral microbiota of mice was further analyzed by 16S rRNA sequencing, microbial culture and qPCR.ResultsIrradiation induced conspicuous mucositis in the oral cavity of mice. S. salivarius K12 treatment was beneficial for the healing of RIOM, as reflected by reduced ulcer size, increased basal layer epithelial cellularity and mucosal thickness, and elevated epithelial proliferation and attenuated apoptosis. RIOM mice presented significant oral microbial dysbiosis, with an overgrowth of oral anaerobes. S. salivarius K12 treatment reconstituted the oral microbiota and decreased the abundance of oral anaerobes of RIOM mice. In addition, S. salivarius K12 treatment inhibited NI1060 in Pasteurella genus and downregulated the expression of nitrate reductase.ConclusionsS. salivarius K12 treatment can alleviate RIOM and reconstituted the dysbiotic oral microbiota in mice. S. salivarius K12 may represent a promising adjuvant treatment to improve the quality of life of cancer patients receiving radiotherapy.
| S-EPMC8213397 | biostudies-literature