Search Results (56)

Background: Cachexia worsens prognosis, quality of life and chemotherapy treatment compliance of patients with lung cancer. Chemotherapy-induced cachexia has also been implicated in lowered mortality. This study aimed to evaluate the frequency of cachexia-related measures and symptoms as outcomes in lung cancer chemotherapy trial protocols and to examine how key trial characteristics influence them. Method: We conducted a cross-sectional data analysis of randomised controlled chemotherapy trials of lung cancer registered in four public trial registries between 2012 and 2023. Trial outcome measures included overall survival, treatment toxicity/side effects and cachexia-related indicators such as physical activity, weight/body mass index (BMI), dietary limitations, caloric intake and lean muscle mass. Symptom-related outcomes, including appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, dysphagia, dyspnoea and oral mucositis, were also extracted. Additionally, the number and type of performance status and assessment tool were recorded. Data were summarised descriptively. Chi-square tests were used to examine associations between trial outcomes and characteristics including cancer type, trial location, lead investigator/funding source, assessment tools and trial commencement year. A p < 0.05 was considered statistically significance. Results: Of the 335 trial protocols (non-small cell (87.2%) and small cell (12.8%)), most were from Europe (50.4%). The trial lead investigator was from industry (56.7%) followed by academia (25.1%). Allied health professional involvement was minimal (0.6%). Trial protocols mostly recorded overall survival (96.4%) and toxicity (83.9%). However, physical activity, weight/BMI, dysphagia, dyspnoea and oral mucositis were recorded in <30%, with dietary limitations, caloric intake and lean muscle mass recorded in <3% of the trials. Measures and symptoms were not associated with cancer type. Trial location was associated with the measures toxicity, physical activity and caloric intake and all symptoms. Lead investigator was associated with the measures toxicity and weight/BMI and all symptoms except for dyspnoea. Performance status and assessment tools were mentioned in 93.4% and 41.8% of the trials, respectively, with significant associations between assessment tools and outcomes, except for weight/BMI, dietary limitations, lean muscle mass, dysphagia and oral mucositis. There was a significant trend with trial commencement year for the measures physical activity (p = 0.002) and weight/BMI (p = 0.000) and all symptoms, except for appetite loss (p = 0.115) and pain (p = 0.433). Conclusions: While the reporting of measures and outcomes was generally higher compared to gastrointestinal chemotherapy cancer trials, it still faced significant under-reporting. Assessment tools should include cachexia-specific symptoms to accurately assess the quality of life in patients with lung cancer undergoing chemotherapy clinical trials. Full article

Cisplatin (CDDP) is an anticancer drug that is frequently used to treat head and neck cancers; however, it may cause oral mucositis. The discontinuation of CDDP may be required for some patients with a severe status, and the control of oral mucositis is extremely important. β-Cryptoxanthin (β-cry), a carotenoid, exerts anti-inflammatory effects. Its inhibition of 5-FU-induced inflammatory responses was recently demonstrated. However, the effects of β-cry on CDDP-induced oral mucositis remain unclear. In the present study, we stimulated human oral mucosa-derived keratinocytes (hOMK) and fibroblasts (hOMF) with CDDP, added β-cry, and examined its effects, with a focus on the production of inflammatory cytokines, matrix metalloproteinase (MMPs), and reactive oxygen species (ROS). CDDP increased the mRNA expression and production of inflammatory cytokines and MMPs both in hOMK and hOMF. However, increases in IL-6 and MMP-9 mRNA expression levels and IL-6 production in CDDP-treated hOMK and hOMF were inhibited by β-cry. Furthermore, the production of ROS and the rate of SA-β-gal-positive cells were increased by CDDP, but were not affected by β-cry. CDDP may induce oral mucositis by increasing the levels of inflammatory cytokines, MMPs, and ROS. β-cry partially inhibited CDDP-induced increases in inflammatory cytokines and MMPs, suggesting its potential to attenuate the symptoms of chemotherapy-related oral mucositis. Full article

The human papillomavirus type 16 (HPV 16) is a high-risk human papillomavirus strain commonly associated with oropharyngeal cancers, including lymph node involvement. The treatment for HPV 16-related tonsil cancer, commonly involving surgery, radiation, and chemotherapy, presents significant challenges. Complications such as oral mucositis, xerostomia, dysphagia, dysgeusia, hypogeusia, impaired gustatory function, and significant weight loss frequently arise, leading to reduced nutritional intake, impaired healing, and recovery progression. These challenges underscore the need for supportive interventions to enhance rehabilitation and the post-recovery period, improve treatment tolerance, and maintain quality of life. Objective: This single-subject study examines a 67-year-old male patient diagnosed with a T1N3b (small primary tumor with advanced lump node involvement) associated with HPV 16 positivity, indicating a virus-associated oncogenesis. Methods: The patient underwent radiation therapy and chemotherapy, leading to treatment-associated side effects. After having dietary drinks for daily nourishment, the patient routinely incorporated oral bio extra virgin olive oil (BEVOO) to cope with indicated challenges. Results: Body composition and metabolic parameters showed treatment-induced declines, followed by substantial but not complete recovery during follow-up examination. Visual Analog Scale (VAS) scores reflected gradual improvements in dysphagia, xerostomia, mucositis, and subtle but ongoing enhancement of the dysgeusia, gustatory perception, and oral palatability. The BEVOO supplementation and mindfulness were associated with positive recovery trends. Additional variables could have impacted the outcomes, preceding and throughout treatment, including the patient’s cognitive and somatic health, environmental conditions, dietary habits, individual attitudes toward recovery, physical activity, and patient way of life. Conclusions: These results emphasize the need for additional research employing a comprehensive, multi-factorial framework that accounts for the complex interplay of physiological, psycho-social, and environmental contributors. More extensive, more diverse studies are essential to confirm these observations and substantiate the role of BEVOO as a supportive intervention in cancer recovery. Full article

Objectives: Mucositis is a debilitating side effect of cancer therapy that adversely affects quality of life, cost of care, and the outcome of cancer therapy. Oral mucositis-related pain may be treated with numerous modalities but often includes opioids. The effects of opiate treatment on painful UM and its overall influence on the burden of illness (BOI) in cancer patients remain unknown. Methods: This study utilized the 2017 United States (US) National Inpatient Sample (NIS) database. The exposure was opioid treatment for chemo-induced ulcerative mucositis (UM), oral mucositis-induced pain, and the main outcomes included in-hospital mortality and BOI, length of hospital stays (LOS), and total hospital charges. Multivariable regression analysis was used to examine the relationship between outcomes and the key independent variable, opioid use, adjusting for propensity scores. Results: In the propensity score-adjusted analysis, UM patients with opioid treatment had 0.51 times lower total charges (95% CI: 0.42–0.76) and 0.67 times shorter LOS (95% CI: 0.51–0.87) than the UM patients without opioid treatment. However, there was no association between opioid treatment and in-hospital mortality. In the sensitivity analysis, the effect estimates were comparable in the propensity score-adjusted analysis, the decile-adjusted model, and the full model with the non-propensity score estimated method. Conclusions: Cancer patients with chemotherapy-induced UM-prescribed opioid analgesics for treating pain are associated with a lower BOI. Opioid pain medications are commonly provided to cancer survivors; estimating the BOI among them is crucial in supportive care research. Full article

Background/Objectives: Oral mucositis (OM) is a common and debilitating side effect of cancer therapy, characterized by ulceration or inflammation of the oral mucosa. This study evaluates the preclinical efficacy of curcumin-loaded bicosome systems (cur-BS) in mitigating chemotherapy-induced OM in mice. Methods: BS were prepared using a combination of 1,2-di-palmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), α-tocopherol, and curcumin, encapsulated within liposomal vesicles. Three formulations with different curcumin concentrations (180, 540, and 900 μM) were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), appearance, and morphology. The formulation with the highest concentration (cur-BS 5×) was selected for ex vivo permeability studies, release profile analysis, and in vitro anti-inflammatory efficacy. OM was induced in mice using 5-fluorouracil (5-FU) and acetic acid. Cur-BS 5× was compared to the commercial product Dentoxol^®. Results: The results showed that cur-BS 5× provided sustained release through a mechanism involving both diffusion and matrix relaxation, enhancing curcumin retention in deeper skin layers. Treatment with cur-BS 5× downregulated the expression of inflammatory markers (IL-1β and TNF-α). Macroscopic assessments demonstrated that both cur-BS 5× and Dentoxol^® reduced OM severity, with the greatest improvement observed between days 6 and 9. By day 24, OM scores were 1.25 ± 0.5 for cur-BS 5× and 1.0 ± 0.0 for Dentoxol^®, indicating effectiveness in both treatments. However, histological analysis revealed superior tissue recovery with cur-BS 5×, showing better epithelial structure and reduced inflammation. Cur-BS 5×-treated mice also exhibited greater weight recovery and higher survival rates compared to the Dentoxol^® group. Conclusions: These findings suggest that cur-BS 5× may enhance OM treatment, offering outcomes comparable to or better than those of Dentoxol^®. Full article

Background/Objectives: Oral mucositis (OM) is the most common acute complication among cancer patients. It initially manifests as an inflammatory process, beginning with erythema and edema of the oral mucosa, progressing to erosive lesions, and ultimately leading to highly painful ulcers. This systematic review seeks to evaluate the efficacy of preventive PBM protocols in mitigating chemotherapy-induced OM. Methods: The PRISMA guidelines were followed. The search was conducted in August 2024 in the following databases: Pubmed/Medline, Scopus, WoS, Cochrane, SciELO, BDTD, and BVS/IBECS. Only randomized clinical trials that utilized preventive photobiomodulation protocols in chemotherapy patients were included. All studies involving patients previously treated with radiation therapy were excluded. The Joanna Briggs Institute tool was employed for risk of bias analysis. Results: The total sample size consisted of 828 patients aged between 1 and 84 years. There was no predisposition based on gender or age. When the patients were evaluated under preventive protocols, some cases of mucositis manifested in a total of 339 cases. Of the total number of patients in the 13 selected studies (n = 828), 40.94% developed oral mucositis over the course of chemotherapy cycles. Comparing the experimental and control groups, 211 patients who did not receive preventive laser treatment developed oral mucositis; in contrast, only 128 in the experimental group did. Eighty-five percent of the studies exhibited a low risk of bias. Conclusions: Preventively applied photobiomodulation proves effective in minimizing or even preventing the manifestation of oral mucositis and reducing the severity of lesions that arise during oncological treatment. Registration PROSPERO (CRD42023465329). Full article

Oral mucositis associated with candidiasis can causes systemic candidemia, posing a risk to cancer patients administered antineoplastic therapy. Cold atmospheric pressure plasma jets (CAPPJs) have antifungal and anti-inflammatory properties. This study evaluated the effects CAPPJs in preventing systemic fungal dissemination in a murine model of oral mucositis associated with candidiasis. Forty Wistar rats were divided into groups: CAPPJs (treated) and non-treated controls (for comparison), with subgroups subject to 24 and 72 h of treatment (n = 10 each). Four cycles of chemotherapy (cisplatin and 5-fluorouracil (5-FU)) were administered, followed by oral inoculation of Candida albicans for 3 days. Mucosal damage was induced on the lateral side of tongue with 50% acetic acid. CAPPJ treatment was performed on the lesion for 5 min (2 days). Body weight was assessed daily. Fungal dissemination was conducted using organ macerates and plated on Sabouraud Agar with chloramphenicol. Blood samples were obtained for blood count tests. Chemotherapy affected the general health of the animals, as evidenced by body weight loss. Treatment with CAPPJs showed an inhibitory effect on C. albicans, with a significant reduction in fungal recovery from the tongue after 24 h (p < 0.05). Interestingly, systemic fungal dissemination was significantly reduced after 24 and 72 h of treatment when compared to control (p < 0.05). Taken together, these results suggest that CAPPJs have potential for clinical application in patients with oral mucositis at risk of candidemia. Full article

The study aims to investigate the effects of curcumin on radiation/chemotherapy-induced oral mucositis (R/CIOM) and preliminarily explore its mechanism. Randomized controlled trials were identified from the PubMed, Embase, Web of Science, Cochrane Library, Medline, and Google Scholar databases. RevMan 5.4 was used for statistical analysis to calculate the combined risk ratios (RRs). The mechanism was analyzed through network pharmacology, molecular docking, and a molecular dynamics simulation. The targets of curcumin were collected in HERB, PharmMapper, Targetnet, Swiss Target Prediction, and SuperPred. OMIM, GeneCards, and Disgenet were used to collect relevant targets for R/CIOM. Cytoscape software 3.8.0 was used to construct the component-target-pathway network. Protein–Protein Interaction (PPI) networks were constructed using the STRING database. GO and KEGG enrichment analyses were performed by Metascape. AutoDock Vina 4.2 software was used for molecular docking. The molecular dynamics simulation was performed by Gromacs v2022.03. It is found that 12 studies involving 565 patients were included. Meta-analyses showed that curcumin reduced the incidence of severe R/CIOM (RR 0.42 [0.24, 0.75]) and the mean severity of R/CIOM (MD -0.93 [−1.34, −0.52]). Eleven core target genes were identified in the treatment of R/CIOM with curcumin. The results of molecular docking and the molecular dynamics simulation showed that curcumin had strong binding energy and stability with target proteins including MAPK3, SRC, and TNF. Overall, these findings suggest curcumin can effectively improve severe R/CIOM, perhaps by affecting MAPK3, SRC, and TNF. Full article

Cancer patients face increased susceptibility to invasive infections, primarily due to ulcerative lesions on mucosal surfaces and immune suppression resulting from chemotherapy. Pseudomonas aeruginosa (P. aeruginosa) bacteremia is notorious for its rapid progression into fatal sepsis, posing a significant threat to cancer patients, particularly those experiencing chemotherapy-induced neutropenia. This bacterial infection contributes significantly to morbidity and mortality rates among such individuals. Our latest report showed the mutually beneficial effects of postbiotic butyrate on 1,25-dihydroxyvitamin D3 (1,25D3)-controlled innate immunity during Salmonella colitis. Hence, we investigated the impact of butyrate and 1,25D3 on chemotherapy-induced gut-derived P. aeruginosa sepsis in mice. The chemotherapy-induced gut-derived P. aeruginosa sepsis model was established through oral administration of 1 × 10⁷ CFU of the P. aeruginosa wild-type strain PAO1 in C57BL/6 mice undergoing chemotherapy. Throughout the infection process, mice were orally administered butyrate and/or 1,25D3. Our observations revealed that the combined action of butyrate and 1,25D3 led to a reduction in the severity of colitis and the invasion of P. aeruginosa into the liver and spleen of the mice. This reduction was attributed to an enhancement in the expression of defensive cytokines and antimicrobial peptides within the cecum, coupled with decreased levels of zonulin and claudin-2 proteins in the mucosal lining. These effects were notably more pronounced when compared to treatments administered individually. This study unveils a promising alternative therapy that involves combining postbiotics and 1,25D3 for treating chemotherapy-induced gut-derived P. aeruginosa sepsis. Full article

Pseudomonas aeruginosa (P. aeruginosa) is a leading cause of nosocomial infections associated with a high mortality rate and represents a serious threat to human health and the increasing frequency of antimicrobial resistance. Cancer patients are more vulnerable to invasive infection due to ulcerative lesions in mucosal surfaces and immune suppression secondary to chemotherapy. In our in vitro study, we observed that probiotics have the potential to yield beneficial effects on intestinal epithelial cells infected with P. aeruginosa. Additionally, probiotics were found to confer advantageous effects on the innate immunity of mice suffering from Salmonella-induced colitis. As a result, we sought to investigate the impact of probiotics on gut-derived P. aeruginosa sepsis induced by chemotherapy. Following chemotherapy, gut-derived P. aeruginosa sepsis was induced in female C57BL/6 mice aged 6–8 weeks, which were raised under specific-pathogen-free (SPF) conditions in an animal center. Prior to the induction of the sepsis model, the mice were administered 1 × 10⁸ colony-forming units (CFU) of the probiotics, namely Lactobacillus rhamnosus GG (LGG) and Bifidobacterium longum (BL) via oral gavage. We observed that LGG or BL amplified the inflammatory mRNA expression in mice undergoing chemotherapy and suffering from gut-derived P. aeruginosa sepsis. This led to a heightened severity of colitis, as indicated by histological examination. Meanwhile, there was a notable decrease in the expression of antimicrobial peptide mRNA along with reduced levels of zonulin and claudin-2 protein staining within mucosal tissue. These alterations facilitated the translocation of bacteria to the liver, spleen, and bloodstream. To our astonishment, the introduction of probiotics exacerbated gut-derived P. aeruginosa sepsis in mice undergoing chemotherapy. Conclusively, we must be prudent when using probiotics in mice receiving chemotherapy complicated with gut-derived P. aeruginosa sepsis. Full article

Oral Mucositis (OM) is the most common side effect due to chemotherapy and radiotherapy, which are the conventional treatment options for head and neck cancers. OM is a severe inflammatory condition characterized by multifactorial etiopathogenesis. It further negatively affects patients’ quality of life by severe impairment of normal oral functions. Consequently, it is mandatory to identify new effective therapeutic approaches to both prevent and treat OM while also avoiding any recurrence. Polyphenols recently attracted the interest of the scientific community due to their low toxicity and wide range of biological activities making them ideal candidates for several applications in the odontostomatological field, particularly against OM. This review collects the in vivo studies and the clinical trials conducted over the past 13 years evaluating the preventive and curative effects of several polyphenolic compounds towards chemo- and radiotherapy-induced OM, both when administered alone or as a plant-extracted phytocomplex. The literature fully confirms the usefulness of these molecules, thus opening the possibility of their clinical application. However, polyphenol limitations (e.g., unfavourable physicochemical properties and susceptibility to degradation) have emerged. Consequently, the interest of the scientific community should be focused on developing innovative delivery systems able to stabilize polyphenols, thus facilitating topical administration and maximizing their efficacy. Full article

Cancer chemotherapy has allowed many patients to survive, but not without risks derived from its adverse effects. Drugs, such as 5-fluorouracil, irinotecan, oxaliplatin, methotrexate, and others, as well as different drug combinations trigger intestinal mucositis that may cause or contribute to anorexia, pain, diarrhea, weight loss, systemic infections, and even death. Dysbiosis is a hallmark of chemotherapy-induced intestinal mucositis and diarrhea, and, therefore, strategies aimed at modulating intestinal microbiota may be useful to counteract and prevent those dreadful effects. This narrative review offers an overview of the studies performed to test the efficacy of probiotics and probiotic-like agents against chemotherapy-induced intestinal mucositis and its consequences. Microbiota modulation through the oral administration of different probiotics (mainly strains of Lactobacillus and Bifidobacterium), probiotic mixtures, synbiotics, postbiotics, and paraprobiotics has been tested in different animal models and in some clinical trials. Regulation of dysbiosis, modulation of epithelial barrier permeability, anti-inflammatory effects, modulation of host immune response, reduction of oxidative stress, or prevention of apoptosis are the main mechanisms involved in their beneficial effects. However, the findings are limited by the great heterogeneity of the preclinical studies and the relative lack of studies in immunocompromised animals, as well as the scarce availability of results from clinical trials. Despite this, the results accumulated so far are promising. Hopefully, with the aid of these agents, intestinal mucositis will be less impactful to the cancer patient in the near future. Full article

Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular damage. Notably, oxidative stress plays a critical role in the pathogenesis of a number of oral mucosal diseases, including oral mucositis, which remains one of cancer treatments’ most common side effects. We have shown previously that oral keratinocytes are remarkably sensitive to oxidative stress, and this may hinder the development and reproducibility of epithelial cell-based models of oral disease. Here, we examined the oxidative stress signatures that parallel oral toxicity by reproducing the initial events taking place during cancer treatment-induced oral mucositis. We used three oral epithelial cell lines (an immortalized normal human oral keratinocyte cell line, OKF6, and malignant oral keratinocytes, H357 and H400), as well as a mouse model of mucositis. The cells were subjected to increasing oxidative stress by incubation with hydrogen peroxide (H₂O₂) at concentrations of 100 μM up to 1200 μM, for up to 24 h, and ROS production and real-time kinetics of oxidative stress were investigated using fluorescent dye-based probes. Cell viability was assessed using a trypan blue exclusion assay, a fluorescence-based live–dead assay, and a fluorometric cytotoxicity assay (FCA), while morphological changes were analyzed by means of a phase-contrast inverted microscope. Static and dynamic real-time detection of the redox changes in keratinocytes showed a time-dependent increase of ROS production during oxidative stress-induced epithelial injury. The survival rates of oral epithelial cells were significantly affected after exposure to oxidative stress in a dose- and cell line-dependent manner. Values of TC50 of 800 μM, 800 μM, and 400 μM were reported for H400 cells (54.21 ± 9.04, p < 0.01), H357 cells (53.48 ± 4.01, p < 0.01), and OKF6 cells (48.64 ± 3.09, p < 0.01), respectively. Oxidative stress markers (MPO and MDA) were also significantly increased in oral tissues in our dual mouse model of chemotherapy-induced mucositis. In summary, we characterized and validated an oxidative stress model in human oral keratinocytes and identified optimal experimental conditions for the study of oxidative stress-induced oral epithelial toxicity. Full article

Pain from radiation-therapy-induced oral mucositis during head-neck cancer treatment is aggravated by concurrent chemotherapy and commonly fails traditional treatments. To explore safe and sustainable alternatives, we investigated methylene blue oral rinse to reduce radiation-therapy-related oral mucositis pain. For this, we conducted a retrospective observational cohort study in a tertiary-care academic care cancer center including 85 patients with refractory oral mucositis pain during radiation therapy for head-neck cancer. Changes in pain (scale 0–10), oral function burden (scale 0–6) and requirement for percutaneous endoscopic gastrostomy tube placement were measured. Among 58 patients, 60% received radiation therapy alone and 40% received concurrent chemotherapy-radiation therapy. Methylene blue oral rinse (MBOR) significantly decreased oral mucositis pain for at least 6.2 h (median + SD 8 ± 1.68 before vs. 2 ± 2.20 after; p < 0.0001) and oral function burden (3.5 ± 1.33 before vs. 0 ± 0.86 after; p < 0.0001). Eleven patients (19%) had percutaneous endoscopic gastrostomy tubes placed before using methylene blue oral rinse; subsequently, four (36%) resumed oral alimentation after methylene blue oral rinse. Two patients (3%) required percutaneous endoscopic gastrostomy tubes despite methylene blue oral rinse. Minimal adverse events were reported (n = 9, 15%). Our study showed that methylene blue oral rinse was an effective and safe topical treatment for opioid-refractory oral pain from oral mucositis associated with radiation therapy for head-neck cancer. Full article

Oral mucositis is a common and debilitating side effect induced by stem cell transplantation that is experienced by cancer patients undergoing chemotherapy or radiation therapy. This condition involves inflammation and ulceration of the oral mucosa, leading to pain, difficulty with eating and speaking, and an increased risk of infections. Mucositis not only compromises the quality of life for cancer patients, but also affects treatment outcomes and may necessitate dose reductions or treatment delays. This scientific article provides a comprehensive overview of mucositis. The purpose of this literature review with a meta-analysis is to evaluate the efficacy of laser therapy in treating post-transplant mucositis. Materials and methods: A search of the literature from 3 May 2023 was carried out on three online databases, PubMed, Scopus, and Web of Science. Only studies that treated patients with laser therapy were considered; only studies with the placebo-treated control group were considered. Review Manager version 5.2.8 (Cochrane Collaboration) was used for the pooled analysis. We measured the std. mean difference between the two groups (laser and placebo). Results: There were 230 papers included in this review. Two hundred twenty-seven were excluded. Furthermore, a manual search was performed. After the search phase, three articles were considered in the study. The overall effect showed differences in the degree of mucositis in the laser-treated patients compared with the placebo group. The meta-analysis shows a reduction in the degree of mucositis in the patients treated with laser therapy (std. mean difference −1.34 [−1.98; −0.98]; C.I. 95%). Conclusions: The application of laser therapy results in decreased severity of oral mucositis from radiation and chemotherapy. Our study shows that the application of low-level laser therapy in the treatment of transplant mucositis has excellent efficacy in relieving the symptoms and severity of mucositis. Full article