Efficacy of Intravitreal Injections Anti-Vascular Endothelial Growth Factor Treatment for Radiation Retinopathy: A Systematic Review and Meta-analysis.

PURPOSE: This study aims to appraise the therapeutic effectiveness of intravitreal injections anti-vascular endothelial growth factor (anti-VEGF) vs alternative therapies in managing radiation retinopathy (RR). DESIGN: Systematic review and meta-analysis. METHODS: We obtained comprehensive data retrieval using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library from their inception until December 15, 2023. This review included randomized controlled trials (RCTs) and nonrandomized studies (NRSs) reporting on best-corrected visual acuity (BCVA) among RR patients treated with intravitreal anti-VEGF. Study selection and data extraction were meticulously performed by 2 independent reviewers. The Cochrane Risk of Bias Tool 2.0 (RoB 2.0) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) scales were utilized for bias risk assessment. Quantification of heterogeneity was executed using Q, H, and I2 statistics. The primary endpoint was the BCVA at the final observation point of each study. Secondary endpoints included central retinal thickness (CRT), foveal avascular zone (FAZ) area, and capillary density (CD) at the level of superficial capillary plexus. Subgroup analyses were undertaken to explore potential heterogeneity sources possibly due to treatment duration and study design. Sensitivity analyses were conducted to ascertain result stability. RESULTS: This analysis incorporated 7 studies (including 3 RCTs) encompassing 922 patients afflicted with RR. Relative to other treatment modalities, intravitreal anti-VEGF therapy was associated with a statistically significant mean decrease in BCVA of -0.34 logMAR (95% CI, -0.39 to -0.30 logMAR; I2 = 87.70%; P < .001), and a substantial reduction in CRT of -34.65 µm (95% CI, -50.70 to -18.60 µm; I2 = 30.40%; P < .001). Additionally, a reduction in the FAZ area by -0.69 mm² (95% CI, -0.91 to -0.46 mm², I2 = 0%; P < .001) was observed. A positive tendency was noted in CD at the superficial capillary plexus between anti-VEGF and other therapeutic interventions. CONCLUSIONS: Intravitreal anti-VEGF injections, in comparison to other treatments, demonstrate superior efficacy in enhancing BCVA and reducing CRT, thereby underscoring the potential of anti-VEGF in ameliorating radiation retinopathy outcomes. However, the conclusions are constrained by the incorporation of data from some NRSs and the small sample sizes.

Vitamin D3 and its Potential to Ameliorate Chemical and Radiation-Induced Skin Injury During Cancer Therapy.

Skin injury and dermatitis are common complications following chemotherapy and radiation administration for cancer treatment. Symptomatic relief of these complications is limited to slow-acting therapies and often results in holding or modifying cancer therapy that may impact patient outcomes. The off-label use of oral high dose vitamin D3 has demonstrated rapid clinical improvement in skin inflammation and swelling in both chemotherapy and radiation-induced injury. Furthermore, vitamin D3 has been shown to downregulate pro-inflammatory pathways and cytokines, including NFkB, and CCL2, as well as CCL20, which are not only involved in tissue injury, but may confer resistance to cancer treatment. In this paper, we discuss 2 patients with acute radiation dermatitis and acute radiation recall dermatitis following chemotherapy who received 50 000 - 100 000 IU of oral high dose vitamin D3 with improvement in their symptoms. These findings may indicate the potential use of vitamin D as a therapeutic intervention and future target for studying skin healing following chemotherapy and/ or radiation-induced cutaneous toxicity.

Oral glutamine: Is there a role in the amelioration of radiation-induced mucositis? A prospective case-control study at a tertiary care centre in North India.

BACKGROUND: The most frequently occurring painful and dose-limiting side effect of radiation therapy (RT) to the head and neck region is oral mucositis (OM). Several studies demonstrated that glutamine may reduce the severity and the duration of OM significantly during RT and chemo-radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: Between January 2021 and August 2022, a prospective single institutional case-control study compared the efficacy and safety of oral glutamine on radiation-induced mucositis in patients with HNC. Of 60 biopsy-proven patients with HNC, 30 patients in the study arm received oral glutamine suspension (10 g in 500 mL of water) orally once daily, 2 hours before RT, receiving definitive or adjuvant RT and chemo-radiotherapy, while as 30 patients in the control arm received placebo with the same dose and schedule (n = 30 in the study arm and n = 30 in the control arm). RESULTS AND ANALYSIS: A total of 27 (90%) in the glutamine arm and 28 (93.33%) patients in the control arm developed mucositis. Grade 3 mucositis (13.33%) and Grade 4 mucositis (6.66%), respectively, were significantly less ( P = .040 and P = .004) in the glutamine arm. The mean duration of grade 3 and grade 4 mucositis was significantly less in the glutamine arm (8.94 days in the study arm vs. 14.54 in the control arm; P = .0001). The mean time of onset of OM was significantly delayed in the glutamine arm in comparison to the control arm with P < .001. CONCLUSION: Glutamine delays the onset of OM and decreases the severity of OM in patients of HNC receiving RT with or without chemotherapy.

Chelation Modeling of a Plutonium-238 Inhalation Incident Treated with Delayed DTPA.

This work describes an analysis, using a previously established chelation model, of the bioassay data collected from a worker who received delayed chelation therapy following a plutonium-238 inhalation. The details of the case have already been described in two publications. The individual was treated with Ca-DTPA via multiple intravenous injections and then nebulizations beginning several months after the intake and continuing for four years. The exact date and circumstances of the intake are unknown. However, interviews with the worker suggested that the intake occurred via inhalation of a soluble plutonium compound. The worker provided daily urine and fecal bioassay samples throughout the chelation treatment protocol, including samples collected before, during, and after the administration of Ca-DTPA. Unlike the previous two publications presenting this case, the current analysis explicitly models the combined biokinetics of the plutonium-DTPA chelate. Using the previously established chelation model, it was possible to fit the data through optimizing only the intake (day and magnitude), solubility, and absorbed fraction of nebulized Ca-DTPA. This work supports the hypothesis that the efficacy of the delayed chelation treatment observed in this case results mainly from chelation of cell-internalized plutonium by Ca-DTPA (intracellular chelation). It also demonstrates the validity of the previously established chelation model. As the bioassay data were modified to ensure data anonymization, the calculation of the "true" committed effective dose was not possible. However, the treatment-induced dose inhibition (in percentage) was calculated.

Protective effects of Yiqi jiedu decoction on ionizing radiation-induced spermatogenic cell injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Ionizing radiation (IR) has found widespread application in modern medicine. As a result, radiotherapy inevitably causes spermatogenic cell injury. Many Chinese herbal prescriptions or natural extracts have the potential to protect against radiation injury. AIM OF THE STUDY: We used GC-2spd cells to investigate the effects and potential mechanisms of YQJD decoction on protecting spermatogenic cells from ionizing radiation injury. MATERIALS AND METHODS: Firstly, the GC-2spd cells were irradiated with 60Co γ-rays (1 Gy, 2 Gy, 4 Gy and 8 Gy) to establish an in vitro model of radiation injury. After that, Cells were divided into six groups: negative control group (NC group), model group (IR group), positive drug group (IRA group), high-dose YQJD decoction (IRH group), medium-dose YQJD decoction (IRM group), and low-dose YQJD decoction group (IRL group). DNA damage, oxidative damage and inflammatory factors were measured. Cell apoptosis and cell cycle were detected by Flow cytometry. Transmission electron microscopy was performed to observe the morphological changes. RESULTS: After irradiation with 60CO γ-ray, the results indicated that the damage of spermatocyte was significantly induced by radiation exposure over 4 Gy. Furthermore, ionizing radiation could make DNA damage and oxidative stress in in GC-2spd cells. In addition, 60CO γ-ray also caused the increase of IL-1ß, IL-6 and TNF-α and the change of cell cycle. However, the application of YQJD decoction inhibited the damage and apoptosis of GC-2spd cells in the aspects of anti-oxidation, promoting DNA damage repair and regulating inflammatory reaction. CONCLUSIONS: Taken together, the protective effects of YQJD decoction on 60CO γ-ray induced spermatocyte injury were confirmed in this study. This exploration might provide a new strategy for the application of Chinese herbs in radioprotection.

Centella asiatica-Derived Endothelial Paracrine Restores Epithelial Barrier Dysfunction in Radiation-Induced Enteritis.

Radiation-induced enteritis is frequently observed following radiotherapy for cancer or occurs due to radiation exposure in a nuclear accident. The loss of the epithelial integrity leads to 'leaky gut', so recovery of damaged epithelium is an important strategy in therapeutic trials. Centella asiatica (CA), a traditional herbal medicine, is widely used for wound healing by protecting against endothelial damage. In this study, we investigated the radio-mitigating effect of CA, focusing on the crosstalk between endothelial and epithelial cells. CA treatment relieved radiation-induced endothelial dysfunction and mitigated radiation-induced enteritis. In particular, treatment of the conditioned media from CA-treated irradiated endothelial cells recovered radiation-induced epithelial barrier damage. We also determined that epidermal growth factor (EGF) is a critical factor secreted by CA-treated irradiated endothelial cells. Treatment with EGF effectively improved the radiation-induced epithelial barrier dysfunction. We also identified the therapeutic effects of CA-induced endothelial paracrine in a radiation-induced enteritis mouse model with epithelial barrier restoration. Otherwise, CA treatment did not show radioprotective effects on colorectal tumors in vivo. We showed therapeutic effects of CA on radiation-induced enteritis, with the recovery of endothelial and epithelial dysfunction. Thus, our findings suggest that CA is an effective radio-mitigator against radiation-induced enteritis.

Re-Du-Ning injection ameliorates radiation-induced pneumonitis and fibrosis by inhibiting AIM2 inflammasome and epithelial-mesenchymal transition.

BACKGROUND: Radiation-induced lung injury (RILI) is a common side effect in chest radiotherapy patients, and there is no good medicine to treat it. Re-Du-Ning (RDN) injection is a traditional Chinese medicine that is clinically used to treat upper respiratory tract infections and acute bronchitis. RDN has the advantage of high safety and mild side effects. The mechanism of most traditional Chinese medicine preparations is unknown. PURPOSE: To illustrate the mechanisms of RDN for the treatment of RILI. METHODS: Female C57BL/6 mice were used to establish a RILI model via irradiation, and RDN injection was intraperitoneally administered at doses of 5, 10, and 20 ml/kg. The cytokines were measured by ELISA and qPCR. The data related to Absent in melanoma 2 (AIM2) inflammasome were analyzed via ELISA and a network pharmacological approach. In addition, the data related to epithelial-mesenchymal transition (EMT) were analyzed via immunofluorescence, Western blotting, and a network pharmacological approach. RESULTS: RDN robustly alleviated RILI. Meanwhile, RDN downregulated inflammatory cells' infiltration and the expression of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α. Next, the potential molecular mechanisms of RDN were predicted through network pharmacology analysis. RDN may ameliorate radiation pneumonitis (RP) by inhibiting AIM2-mediated pyroptosis. Moreover, RDN treatment inhibited EMT and phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway. The active compounds from Lonicera japonica Thunb. decreased the phosphorylation of Akt. CONCLUSION: These findings demonstrate that RDN, as a traditional Chinese medicine preparation, will be a candidate drug for treating RILI.

A strategy for attenuation of acute radiation-induced lung injury using crocetin from gardenia fruit.

PURPOSE: Radiation-induced lung injury limits the implementation of radiotherapy plans and severely impairs the quality of life. Crocetin has the capability to protect against radiation. This study is aimed at estimate the preventive effect and mechanism of crocetin on acute radiation induced lung injury. METHODS AND MATERIALS: In this study, we offer a strategy for radiation-induced lung injury by using crocetin, an extract of gardenia fruit. Histopathology, transcriptomics, flow cytometry, and other methods have served to examine the effect and mechanism of crocetin on acute radiation-induced lung injury. RESULTS: Crocetin effectively alleviates radiation-induced alveolar wall thickening and alveolar destruction. The number of normal alveoli and lung structure of mice is well protected by the prevention of crocetin. It is found that crocetin inhibits necroptosis to achieve effective radioprotection by down regulating the Tnfrsf10b gene in vitro. CONCLUSION: Crocetin inhibits necroptosis through transcriptional regulation of the Tnfrsf10b gene, thereby preventing radiation-induced lung injury. This work may provide a new strategy for the prevention of lung radiation injury by the extract from Chinese herbal medicine.

Prophylactic management of radiation-induced mucositis using herbal mouthwash in patients with head and neck cancer: an assessor-blinded randomized controlled trial.

OBJECTIVES: Radiation-induced mucositis (RIOM) is one of the most common side effects from head and neck radiotherapy. Several reagents have been introduced to manage the symptom; however, there is still a limited number of effective reagents. Herbal mouthwashes with payayor (Clinacanthus nutans Lindau) and fingerroot (Boesenbergia rotunda) were tested their efficacies in preventing and reducing severity of RIOM in comparison with normal saline with sodium bicarbonate. METHODS: One hundred twenty patients with head and neck cancer undergoing radiotherapy participated in the study and were randomly assigned into three treatment groups using block randomization method. The participants were assigned one of the three mouthwashes for use throughout their radiotherapy course and were assessed for their mucositis scores from week one to six into their radiotherapy course as well as at one-month follow-up. Body mass index was also measured for comparison of nutritional status. RESULTS: The two mouthwashes were similarly effective in prophylaxis of RIOM in term of severity. The averaged mucositis scores were less than two for all groups. For the onset of RIOM, both herbal mouthwashes could slightly delay the symptom but not statistically significant. Patients' body mass index across the three treatment groups was also comparable. The patients were largely satisfied with all the mouthwashes with no clear preference on any of them. CONCLUSIONS: Prophylactic treatment of RIOM using herbal mouthwashes could substitute the current standard of normal saline with bicarbonate. A different formulation of the two herbs could potentially improve the prophylactic outcome. TRIAL REGISTRATION NO: NCT03359187.

The Therapeutic Effect of Acanthopanax senticosus Components on Radiation-Induced Brain Injury Based on the Pharmacokinetics and Neurotransmitters.

Acanthopanax senticosus (AS) is a medicinal and food homologous plant with many biological activities. In this research, we generated a brain injury model by 60Co -γ ray radiation at 4 Gy, and gavaged adult mice with the extract with AS, Acanthopanax senticocus polysaccharides (ASPS), flavones, syringin and eleutheroside E (EE) to explore the therapeutic effect and metabolic characteristics of AS on the brain injury. Behavioral tests and pathological experiments showed that the AS prevented the irradiated mice from learning and memory ability impairment and protected the neurons of irradiated mice. Meanwhile, the functional components of AS increased the antioxidant activity of irradiated mice. Furthermore, we found the changes of neurotransmitters, especially in the EE and syringin groups. Finally, distribution and pharmacokinetic analysis of AS showed that the functional components, especially EE, could exert their therapeutic effects in brain of irradiated mice. This lays a theoretical foundation for the further research on the treatment of radiation-induced brain injury by AS.

UPLC-ESI-MS/MS profiling and hepatoprotective activities of Stevia leaves extract, butanol fraction and stevioside against radiation-induced toxicity in rats.

Stevioside is the major component of Stevia rebaudiana (Bertoni) leaves, family Asteraceae. UPLC-ESI-MS/MS analyses of leaves total methanol extract (TEx) and standardized butanol fraction (BF, 113.5 mg stevioside/g) were performed herein, revealing steviol glycosides, caffeoylquinic acid derivatives, flavonoids, and sesquiterpenoids. Their hepatoprotective activities against radiation-induced toxicity were evaluated compared to pure stevioside. Rats pretreatment with stevioside, TEx, and BF orally for 7 days before subjection to 6.5 Gy whole-body-gamma-irradiation reversed histopathological damages; improved liver functions and restored depleted antioxidants. ALT and reduced-glutathione levels showed insignificant changes, compared to control, by (5.22%, 3.20%, 24.90%) and (-0.47%, -3.95%, -2.63%), respectively. Glutathione-S-transferase, catalase, and MDA levels were significantly ameliorated. Liver tissue molecular profiling showed reduction in elevated TNF-α by 23.83%, 29.06%, 28.34%, respectively, and in NF-kB and COX-2 expression levels via immunohistochemical study. BF showed better hepatoprotective activity than TEx which may be attributed to higher stevioside, flavonoids, and caffeoylquinic acid derivatives content.

Chinese Herbal Medicine to Reduce Radiation-Induced Oral Mucositis in Head and Neck Cancer Patients: Evidence From Population-Based Health Claims.

BACKGROUND: Subjects with head and neck cancer (HNC) often experience post-treatment side effects, particularly radiation-induced oral mucositis (RIOM). This study aimed to explore the association of Chinese herbal medicine use with the sequent risk of RIOM among them. METHODS: This cohort study used a nationwide health insurance database to identify subjects newly diagnosed with HNC, aged 20 to 60 years, who received treatment between 2000 and 2007. Among them, a total of 561 cases received CHM after HNC onset (CHM users); the remaining 2395 cases were non-CHM users. All patients were followed to the end of 2012 to identify any treatment for RIOM as the end point. Cox proportional hazards regression was used to compute the adjusted hazard ratio (aHR) of RIOM by CHM use. RESULTS: During the follow-up period, 183 CHM users and 989 non-CHM users developed RIOM at incidence rates of 40.98 and 57.91 per 1000 person-years, respectively. CHM users had a lower RIOM risk than the non-CHM users (aHR: 0.68; 95% Confidence Interval: 0.58-0.80). The most potent effect was observed in those taking CHM for more than 1 year. Use of Baizhi, Danshen, Shao-Yao-Gan-Cao-Tang, Gan-Lu-Yin, Huangqin, Shu-Jing-Huo-Xue-Tang, and Xin-Yi-Qing-Fei-Tang, was significantly related to a lower risk of RIOM. CONCLUSION: Findings of this study indicated that adding CHM to conventional clinical care could be helpful in protecting those with HNC against the onset of RIOM. Further clinical and mechanistic studies are warranted.

Efficacy of Liangxue Guyuan decoction on radiation-induced intestinal injury in rats via the toll-like receptor 4/myeloid differentiation primary response 88/ nuclear factor-kappa B pathway.

OBJECTIVE: To evaluate the efficacy of Liangxue Guyuan decoction ( LGD) on radiation-induced intestinal injury in rats, and the possible underlying mechanism of action. METHODS: A total of 255 male Sprague-Dawley rats were used. 15 rats were assigned to the control group and the remaining 240 rats were exposed to a 60Co source at a dose of 11 Gy. Irradiated rats were randomly divided into model, dexamethasone (DXM), low-dose LGD (LGDl), and high-dose LGD (LGDh) groups and treated for 11 d. The survival rate, weight of body, intestinal pathology and the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor-kappa B (NF-κB) were recorded. RESULTS: Radiation reduced the survival rate and weight of rats, destroyed the intestinal structure, induced an inflammatory reaction, and increased both protein and mRNA expression of TLR4, MyD88, and NF-κB in ileum. However, LGDh increased the survival rate, inhibited weight loss, alleviated inflammation and improve the expression of TLR4 pathway. CONCLUSION: LGD increased the survival rate and inhibit weight loss of irradiated rats, and reduced inflammation and intestinal injury. The underlying mechanism may involve regulation of the TLR4/MyD88/NF-κB pathway.

Use of the Water-Soluble Contrast Medium Gastrografin in Treatment of Adhesive Small Bowel Obstruction in Patients with and Without Chronic Radiation Enteropathy: A Single-Center Retrospective Study.

BACKGROUND This retrospective cohort study from a single center aimed to compare patient outcomes following the use of the water-soluble contrast medium Gastrografin in the treatment of adhesive small bowel obstruction (ASBO) in patients with and without a history of chronic radiation enteropathy (CRE). MATERIAL AND METHODS Fifty-nine patients with CRE-induced small bowel obstruction (SBO) and 53 patients with ASBO at Jinling Hospital between April 2014 and February 2018 were enrolled. The patients were given 100 ml Gastrografin through a naso-jejunal tube, and erect abdominal X-rays were taken. Risk factors were found to be correlated with successful non-operative management (SNM) through statistical analyses. RESULTS The success rate of conservative treatment was higher in the Gastrografin group than in the control group (P<0.05). The Gastrografin challenge test is predictive of need for surgery in CRE-induced SBO and ASBO (AUC=0.860 and 0.749, respectively). The predictors associated with SNM in the CRE-induced SBO group were the total dose of radiotherapy, the Gastrografin challenge test, and previous operations for SBO. In the ASBO group, the predictors were the Gastrografin challenge test and previous operations for SBO. The operation rate of SBO patients with Gastrografin treatment was significantly lower than that in the control group (P<0.05). CONCLUSIONS The findings from this study showed that the use of Gastrografin effectively resolved ASBO in patients with and without a history of CRE, but a long-term requirement for surgery could not be avoided. The Gastrografin challenge may be a useful test to predict surgical outcomes.

Intravesical Instillation of Kangfuxin Liquid Combined with Thrombin and Epidermal Growth Factor for Radiation-induced Hemorrhagic Cystitis in Patients with Cervical Cancer: A report of 34 cases.

This study aimed to assess the effectiveness and safety of intravesical instillation treatment of Kangfuxin liquid (KFL) combined with thrombin and epidermal growth factor (EGF) for radiation-induced hemorrhagic cystitis (HC) in patients with cervical cancer. A total of 34 patients with radiation-induced HC of grade 2-4 were treated with intravesical instillation of KFL combined with thrombin and EGF until the complete disappearance of hematuria and lower urinary tract symptoms (LUTS). Gentamicin was added if white blood cells were detected and bacterial culture was positive in the urine. All patients were followed up for 2 years to evaluate the clinical efficacy and safety of the treatment regimen. Patients with and without recurrent hematuria (n = 3, 9% and n = 31, 91%, respectively) were completely recovered from hematuria and LUTS by intravesical instillation treatment for 6-22 days. No adverse event was reported during the treatment and the 2-year follow-up for all patients. Thus, intravesical instillation of KFL combined with thrombin and EGF is an effective and safe therapeutic regimen for radiation-induced HC of grade 2-4 in patients with cervical cancer.

Superoxide Dismutase as an Intervention for Radiation Therapy-Associated Toxicities: Review and Profile of Avasopasem Manganese as a Treatment Option for Radiation-Induced Mucositis.

Toxicities associated with radiation therapy are common, symptomatically devastating, and costly. The best chance to effectively mitigate radiation-associated normal tissue side effects are interventions aimed at disrupting the biological cascade, which is the basis for toxicity development, while simultaneously not reducing the beneficial impact of radiation on tumor. Oxidative stress is a key initiator of radiation-associated normal tissue injury as physiologic antioxidant mechanisms are overwhelmed by the accumulation of effects produced by fractionated treatment regimens. And fundamental to this is the generation of superoxide, which is normally removed by superoxide dismutases (SODs). Attempts to supplement the activity of endogenous SOD to prevent radiation-induced normal tissue injury have included the administration of bovine-derived SOD and increasing SOD production using gene transfer, neither of which has resulted in a clinically acceptable therapy. A third approach has been to develop synthetic small molecule dismutase mimetics. This approach has led to the creation and development of avasopasem manganese, a unique and specific dismutase mimetic that, in clinical trials, has shown promising potential to reduce the incidence, severity and duration of severe oral mucositis amongst patients being treated with concomitant chemoradiation for cancers of the head and neck. Further, avasopasem and related analogues have demonstrated mechanism-related antitumor synergy in combination with high dose per fraction radiotherapy, an observation that is also being tested in clinical trials. An ongoing Phase 3 trial seeks to confirm avasopasem manganese as an effective intervention for severe oral mucositis associated with chemoradiation in head and neck cancer patients.

Valproic acid protects intestinal organoids against radiation via NOTCH signaling.

Radiotherapy is a leading treatment for various types of cancer. However, exposure to high-dose ionizing radiation causes acute gastrointestinal injury and gastrointestinal syndrome. This has significant implications for human health, and therefore, radioprotection is a major area of research. Radiation induces the loss of intestinal stem cells; hence, the protection of stem cells expressing LGR5 (a marker of intestinal epithelial stem cells) is a key strategy for the prevention of radiation-induced injury. In this study, we identified valproic acid (VPA) as a potent radioprotector using an intestinal organoid culture system. VPA treatment increased the number of LGR5+ stem cells and organoid regeneration after irradiation. N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, an inhibitor of NOTCH signaling) blocked the radioprotective effects of VPA, indicating that NOTCH signaling is a likely mechanism underlying the observed effects of VPA. In addition, VPA acted as a radiosensitizer via the inhibition of histone deacetylase (HDAC) in a colorectal cancer organoid. These results demonstrate that VPA exerts strong protective effects on LGR5+ stem cells via NOTCH signaling and that the inhibition of NOTCH signaling reduces these protective effects, providing a basis for the improved management of radiation injury.

Potential utility of peptides against damage induced by ionizing radiation.

Radioprotection is the process whereby biological systems are aided against undesirable radiation hazards. Primitive radioprotectors suffered from either having crucial side effects or low efficacy in clinical applications. Therefore, the search for less toxic but more capable radioprotectants has continued for decades. Peptides have been investigated as radioprotectants in a variety of preclinical models both in vitro and in vivo. Peptides exert their influence through scavenging free radicals, modifying cell signaling and inhibiting cell apoptosis. Demonstrating potential in vivo properties, peptide radiation countermeasures might find enough credit for use in humans in the future. This article reviews the potential therapeutic value of currently known radioprotective peptides and attempts to provide a comprehensive source for further scientific research in this area.

Effect of Honey-Lemon Spray Versus Benzydamine Hydrochloride Spray on Radiation-Induced Acute Oral Mucositis in Head and Neck Cancer Patients: A Pilot, Randomized, Double-Blind, Active-Controlled Clinical Trial.

Introduction: Oral mucositis (OM) is the most prevalent side effect in patients with head and neck cancer (HNC). It causes an obvious decrease in quality of life (QoL) in these patients, so different medications have been recommended for OM, however, without optimal response. This randomized trial aimed to assess the effects of a honey-lemon spray compared with benzydamine hydrochloride in prevention of radiation-induced OM in patients with HNC. Materials and Methods: Forty-six patients with HNC received external beam radiotherapy for 5 days per week. Patients were randomized to treatment with either benzydamine hydrochloride spray or honey-lemon spray for 5 weeks and continued for 1 week after the end of treatment. The oral cavity was examined weekly, with a score given to each site based on the degree of mucositis using a 4-point scale, and a mean mucositis score was calculated as the primary outcome. Occurrence of OM, pain, QoL, and adverse effects were defined as secondary outcomes. Patients, therapists, and outcome assessors were blinded to group allocation. Results: No significant group differences occurred in the mucositis score, pain, or QoL. Mucositis occurrence rates were higher in the benzydamine hydrochloride group compared with the honey-lemon group (hazard ratio = 2.1, 95% confidence interval: 1.1 to 4.2). Two patients in the honey-lemon group had mild nausea and burning throat; no adverse effects occurred in the benzydamine hydrochloride group. Conclusions: There were no significant group differences in mucositis severity between patients treated with honey-lemon spray and benzydamine hydrochloride. The potential preventive effects of honey-lemon spray need to be confirmed in further trials. The trial registration number is IRCT20161024030467N1.

Results of a randomized controlled phase III trial: efficacy of polyphenol-containing cystus® tea mouthwash solution for the reduction of mucositis in head and neck cancer patients undergoing external beam radiotherapy.

PURPOSE: To determine the effect of Cystus® tea (Naturprodukte Dr. Pandalis GmbH & Co. KG) as mouthwash compared to sage tea on oral mucositis in patients undergoing radio(chemo)therapy for head and neck cancer. METHODS: In this randomized, prospective phase III study, 60 head and neck cancer patients with primary or postoperative radio(chemo)therapy were included between 04/2012 and 06/2014. They received either sage or Cystus® tea for daily mouthwash under therapy. Mucositis was scored twice a week following the Radiation Therapy Oncology Group and the European Organization for Research and Treatment Cancer (RTOG/EORTC) scoring system. Dental parameters were also recorded. Statistical evaluation of the primary endpoint was performed using t­test and log rank test. RESULTS: Data from 57 patients could be evaluated. Patient characteristics showed no significant difference between the two groups (n = 27 sage; n = 30 Cystus®). A total of 55 patients received the prescribed dose (60-66 Gy postoperative; 70-76.8 Gy primary). Mucositis grade 3 was observed in 23 patients (n = 11 sage; n = 12 Cystus®) and occurred between day 16 and 50 after start of therapy. There was no significant difference between the two groups in latency (p = 0.75) and frequency (p = 0.85) of the occurrence of mucositis grade 3. The self-assessment of the oral mucosa and the tolerability of the tea also showed no significant differences. Occurrence of dental pathologies appeared to increase over time after radiotherapy. CONCLUSION: Cystus® and sage tea have a similar effect on the occurrence of radiation-induced mucositis regarding latency and incidence. Cystus® tea mouthwash solution is tolerated well and can be applied in addition to intensive oral care and hygiene along with the application of fluorides.