-
International Journal of Molecular... Jul 2023In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant... (Review)
Review
In recent years, there has been a noticeable development in oncological treatment, including chemotherapy and biological treatment. Despite their significant effectiveness, they are not free from side effects, such as allergic and dermatological reactions. These reactions can vary in severity and outcome, including potential death. Examples, among others, are type I-IV hypersensitivity reactions of various origins and skin reactions including rashes, itching and redness, but also severe cutaneous syndromes. Due to the therapy used, these may include Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis. In some cases, it is necessary to interrupt therapy, which may result in a poorer outcome and shorten the patient's survival. This paper reviews various types of research documents published since 2016. It aims to systematize the latest knowledge and highlight the need for further research into ways to avoid adverse reactions.
Topics: Humans; Skin; Stevens-Johnson Syndrome; Acute Generalized Exanthematous Pustulosis; Drug Hypersensitivity Syndrome; Eosinophilia
PubMed: 37511017
DOI: 10.3390/ijms241411257 -
Journal of Oral Pathology & Medicine :... Oct 2023The present network meta-analysis aims to answer the question "what is the best topical intervention for the treatment of recurrent aphthous stomatitis that can provide... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The present network meta-analysis aims to answer the question "what is the best topical intervention for the treatment of recurrent aphthous stomatitis that can provide an acceptable pain relief and promote wound healing?"
METHODS
From inception to October 2022, PubMed, Embase, Scopus, Cochrane Library, and China National Knowledge Infrastructure were searched to identify all potentially eligible randomized controlled trials. The primary outcomes were pain scores and/or healing time, while the secondary outcomes were the associated side effects. The Bayesian network meta-analysis accompanied by a random effect model and 95% credible intervals were calculated.
RESULTS
Forty-three randomized controlled trials with a total of 3067 participants, comparing 20 different topical medications, were included. Concerning pain reduction, the network meta-analysis failed to show any statistically significant differences when different topical treatments were compared together or even with a placebo at different time intervals. Except for doxycycline, which showed a statistically significant difference in terms of accelerating healing time, other topical interventions showed no statistically significant differences when compared with placebo or with each other.
CONCLUSION
Within the limitations of the current network meta-analysis, it seems that: A low to moderate quality of evidence showed no superiority of any topical treatment over others concerning pain reduction, although rank probability tests revealed sucralfate, doxycycline, hyaluronic acid, and chamomile as the most efficacious treatment options at different evaluation times. Hence, further well-designed clinical trials with larger sample sizes are warranted. Topical doxycycline was shown to be the most efficacious intervention in promoting healing of recurrent aphthous stomatitis.
Topics: Humans; Stomatitis, Aphthous; Doxycycline; Network Meta-Analysis; Bayes Theorem; Pain
PubMed: 37753744
DOI: 10.1111/jop.13480 -
Oral Oncology Sep 2023Radiation-induced mucositis is the most common, debilitating and painful acute toxicity associated with active treatment in head and neck cancer area, severely affecting... (Review)
Review
Radiation-induced mucositis is the most common, debilitating and painful acute toxicity associated with active treatment in head and neck cancer area, severely affecting more than 65% of patients. Oral microbiota significantly changes during cancer therapy and appears to be involved on its pathophysiology. This review aims to present a comprehensive update of new etiopathogenic factors and treatments that may decrease the incidence of mucositis, mainly modifications of dietary interventions to modify microbiome. Despite advances in recent years, its management is mainly symptomatic opioid-based with variable results on different substances analyzed for its prevention. Immunonutrition seems to play a significant role, particularly the supplementation of compounds such as fatty acids, polyphenols or selected probiotics have shown to promote commensal bacteria diversity and reduced incidence of ulcerative mucositis. Modification of the microbiome is a promising preventive treatment for mucositis although its evidence is still scarce. Large studies are needed to demonstrate the efficacy of interventions on microbiome and its clinical impact on radiation-induced mucositis.
Topics: Humans; Mucositis; Stomatitis; Head and Neck Neoplasms; Radiation Injuries; Microbiota
PubMed: 37399707
DOI: 10.1016/j.oraloncology.2023.106488 -
The Journal of Infectious Diseases Nov 2023The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%-51%. The only licensed filovirus vaccine in the United States,...
BACKGROUND
The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%-51%. The only licensed filovirus vaccine in the United States, Ervebo, consists of a recombinant vesicular stomatitis virus (rVSV) vector that expresses Ebola virus (EBOV) glycoprotein (GP). Ervebo was shown to rapidly protect against fatal Ebola disease in clinical trials; however, the vaccine is only indicated against EBOV. Recent outbreaks of other filoviruses underscore the need for additional vaccine candidates, particularly for BDBV infections.
METHODS
To examine whether the rVSV vaccine candidate rVSVΔG/BDBV-GP could provide therapeutic protection against BDBV, we inoculated seven cynomolgus macaques with 1000 plaque-forming units of BDBV, administering rVSVΔG/BDBV-GP vaccine to 6 of them 20-23 minutes after infection.
RESULTS
Five of the treated animals survived infection (83%) compared to an expected natural survival rate of 21% in this macaque model. All treated animals showed an early circulating immune response, while the untreated animal did not. Surviving animals showed evidence of both GP-specific IgM and IgG production, while animals that succumbed did not produce significant IgG.
CONCLUSIONS
This small, proof-of-concept study demonstrated early treatment with rVSVΔG/BDBV-GP provides a survival benefit in this nonhuman primate model of BDBV infection, perhaps through earlier initiation of adaptive immunity.
Topics: Animals; Hemorrhagic Fever, Ebola; Ebolavirus; Vesicular Stomatitis; Antibodies, Viral; Vesiculovirus; Glycoproteins; Viral Vaccines; Macaca fascicularis; Immunoglobulin G; Ebola Vaccines
PubMed: 37290053
DOI: 10.1093/infdis/jiad207 -
Frontiers in Immunology 2023Metastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint...
A phase I oncolytic virus trial with vesicular stomatitis virus expressing human interferon beta and tyrosinase related protein 1 administered intratumorally and intravenously in uveal melanoma: safety, efficacy, and T cell responses.
INTRODUCTION
Metastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM.
METHODS
We developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNβ-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective.
RESULTS
12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses.
DISCUSSION
Our study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen.
Topics: Animals; Humans; Interferon-beta; Melanoma-Specific Antigens; Monophenol Monooxygenase; Oncolytic Virotherapy; Oncolytic Viruses; T-Lymphocytes; Vesicular Stomatitis; Vesicular stomatitis Indiana virus
PubMed: 38022659
DOI: 10.3389/fimmu.2023.1279387 -
Journal of Oral Biosciences Jun 2024The use of prostheses in the oral cavity creates favorable conditions for Candida colonization, which may subsequently lead to Candida-associated denture stomatitis... (Review)
Review
BACKGROUND
The use of prostheses in the oral cavity creates favorable conditions for Candida colonization, which may subsequently lead to Candida-associated denture stomatitis (CADS). Due to its many contributing factors and frequent relapses, CADS is difficult to manage. Given the rise in drug resistance among fungal species, it is critical to develop new therapeutic approaches, reduce the required dosage of medications, and minimize the toxicity and side effects of therapy.
HIGHLIGHT
Salivary lactoferrin, a multifunctional glycoprotein, is thought to be the first line of defense against microbial invasion of mucosal surfaces.
CONCLUSION
Current research emphasizes the capability of lactoferrin and its derivatives to eliminate a broad spectrum of Candida species. It may be an appealing option for use in monotherapy or in combination with common medications for oral stomatitis treatment. This review provides an overview of the current understanding of lactoferrin's anti-fungal effects in oral candidiasis.
Topics: Lactoferrin; Humans; Stomatitis, Denture; Candidiasis, Oral; Antifungal Agents; Candida
PubMed: 38777122
DOI: 10.1016/j.job.2024.05.007 -
Cell Death & Disease Jul 2023Oral and intestinal mucositis (OIM) are debilitating inflammatory diseases initiated by oxidative stress, resulting in epithelial cell death and are frequently observed...
Oral and intestinal mucositis (OIM) are debilitating inflammatory diseases initiated by oxidative stress, resulting in epithelial cell death and are frequently observed in cancer patients undergoing chemo-radiotherapy. There are currently few preventative strategies for this debilitating condition. Therefore, the development of a safe and effective mucositis mitigating strategy is an unmet medical need. Hyaluronic acid (HA) preparations have been tentatively used in oral mucositis. However, the protective effects of HA in chemotherapy-induced mucositis and their underlying mechanisms remain to be fully elucidated. This study aimed to assess these mechanisms using multiple formulations of enriched HA (Mucosamin), cross-linked (xl-), and non-crosslinked high molecular weight HA (H-MW-HA) in an oxidative stress-induced model of human oral mucosal injury in vitro and an in vivo murine model of 5-flurouracil (5-FU)-induced oral/intestinal mucositis. All tested HA formulations protected against oxidative stress-induced damage in vitro without inducing cytotoxicity, with H-MW-HA also significantly reducing ROS production. Daily supplementation with H-MW-HA in vivo drastically reduced the severity of 5-FU-induced OIM, prevented apoptotic damage and reduced COX-2 enzyme activity in both the oral and intestinal epithelium. In 5-FU-injected mice, HA supplementation also significantly reduced serum levels of IL-6 and the chemokine CXCL1/KC, while the serum antioxidant activity of superoxide dismutase was elevated. Our data suggest that H-MW-HA attenuates 5-FU-induced OIM, at least partly, by impeding apoptosis, inhibiting of oxidative stress and suppressing inflammatory cytokines. This study supports the development of H-MW-HA preparations for preventing OIM in patients receiving chemotherapy.
Topics: Humans; Animals; Mice; Mucositis; Hyaluronic Acid; Molecular Weight; Stomatitis; Apoptosis; Antineoplastic Agents
PubMed: 37479691
DOI: 10.1038/s41419-023-05934-6 -
The Journal of Prosthetic Dentistry Dec 2023Photodynamic therapy is widely used in dentistry, but limited evidence exists regarding its effectiveness in treating denture stomatitis. High resistance to antifungals... (Meta-Analysis)
Meta-Analysis Review
STATEMENT OF PROBLEM
Photodynamic therapy is widely used in dentistry, but limited evidence exists regarding its effectiveness in treating denture stomatitis. High resistance to antifungals has been reported, and photodynamic therapy could be an alternative treatment.
PURPOSE
The purpose of this systematic review and meta-analysis was to evaluate whether photodynamic therapy is effective in reducing denture stomatitis.
MATERIAL AND METHODS
A systematic review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and recorded in the prospective register of systematic reviews (PROSPERO) (CRD42020205589) to answer the population, intervention, control, outcome (PICO) question: "Is photodynamic therapy effective in the treatment of denture stomatitis when compared with the use of antifungal agents?" Electronic searches were performed in databases PubMed/MEDLINE, Cochrane library, and Web of Science for articles published until February 2021 by using the following terms: (denture stomatitis OR oral candidiasis) AND (low-level light therapy OR laser therapy OR lasers OR photodynamic therapies OR photochemotherapy) AND (antifungal drugs OR antifungal agents OR antimicrobial OR treatment). Clinical trials and randomized clinical trials, studies in the English language, and studies comparing antifungal agents with photodynamic therapy were included.
RESULTS
In total, 5 articles were selected for the qualitative analysis and 3 for the meta-analysis. No significant difference was detected between antifungal therapy and photodynamic therapy in the reduction of colony-forming units on the palate. In a subgroup analysis, a significant difference was found in the reduction of colony-forming units on the palate at 15 days and at the denture surface at 30 days.
CONCLUSIONS
Photodynamic therapy is effective in the treatment of denture stomatitis, but after 30 days and 15 days, the antifungals demonstrated better performance.
Topics: Humans; Antifungal Agents; Stomatitis, Denture; Candidiasis, Oral; Photochemotherapy; Anti-Infective Agents
PubMed: 35125209
DOI: 10.1016/j.prosdent.2021.11.028 -
Journal of Virology Sep 2023Oncolytic virus (OV) therapy is a promising virus-based approach against various malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies...
Oncolytic virus (OV) therapy is a promising virus-based approach against various malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies demonstrated that human PDAC cell lines are highly variable in their permissiveness to OVs. Mouse PDAC cell lines, which are widely used for examination of the adaptive immune responses during OV and other cancer therapies, have never been examined systematically for the impact of intertumoral heterogeneity (the differences observed between tumors in different patients) on OV virus efficacy. Here, we examined phenotypically and genotypically three commonly used allograftable mouse PDAC cell lines (C57BL6 genetic background): Panc02 (derived from chemically induced PDAC; also known as Pan02), and two cell lines originated from PDACs developed in two different KPC (Kras, Trp53, and PDX-1-Cre) mouse models. Our study (i) characterized the ability of a widely used attenuated oncolytic vesicular stomatitis virus VSV-ΔM51-GFP to infect, replicate in, and kill mouse PDAC cells; (ii) examined their innate antiviral responses; (iii) compared their permissiveness to a non-attenuated VSV-Mwt-GFP and chemotherapeutic drugs; and (iv) analyzed their karyotype and exome. Mouse PDAC cell lines showed high divergence in their permissiveness to VSV-ΔM51-GFP, which negatively correlated with their abilities to mount innate antiviral responses, while all three cell lines were highly permissive to VSV-Mwt-GFP. No correlation was found between resistance to VSV-ΔM51-GFP and chemotherapy. Also, mouse PDAC cell lines showed high divergence in their karyotype and exome. The exome analysis demonstrated that more VSV-ΔM51-GFP-permissive mouse PDAC cell lines harbor mutations in multiple important antiviral genes, such as TYK2, JAK2, and JAK3. IMPORTANCE Oncolytic virus (OV) therapy is a promising virus-based approach against various malignancies, including pancreatic ductal adenocarcinoma (PDAC). Our previous studies using various human PDAC cell lines demonstrated that they are highly variable in their permissiveness to OVs. In this study, we examined phenotypically and genotypically three commonly used allograftable mouse PDAC cell lines, which are widely used for examination of the adaptive immune responses during cancer therapies. Mouse PDAC cell lines showed high divergence in their permissiveness to oncolytic vesicular stomatitis virus (VSV), which negatively correlated with their abilities to mount innate antiviral responses. Also, we discovered that more VSV-permissive mouse PDAC cell lines harbor mutations in multiple important antiviral genes, such as TYK2, JAK2, and JAK3. Our study provides essential information about three model mouse PDAC cell lines and proposes a novel platform to study OV-based therapies against different PDACs in immunocompetent mice.
Topics: Animals; Humans; Mice; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Interferon Type I; Oncolytic Virotherapy; Oncolytic Viruses; Pancreatic Neoplasms; Vesicular stomatitis Indiana virus
PubMed: 37671865
DOI: 10.1128/jvi.01005-23 -
The Journal of Evidence-based Dental... Sep 2023No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled... (Randomized Controlled Trial)
Randomized Controlled Trial
EFFICACY AND SAFETY OF A DEXAMETHASONE-BASED MOUTHWASH TO PREVENT CHEMOTHERAPY-INDUCED STOMATITIS IN WOMEN WITH BREAST CANCER: A MULTICENTRE, OPEN-LABEL, RANDOMISED PHASE 2 STUDY.
PURPOSE
No standard approach other than oral care is available for preventing chemotherapy-induced stomatitis in patients with breast cancer. In this randomized, controlled phase 2 trial, we aimed to assess the efficacy and safety of a dexamethasone-based mouthwash in preventing chemotherapy-induced stomatitis in patients with early breast cancer.
BASIC PROCEDURES
Patients with breast cancer scheduled for epirubicin and cyclophosphamide (EC) or docetaxel and cyclophosphamide (TC) therapy were selected and allocated in a 1:1 ratio to the intervention and control groups. The intervention group received chemotherapy, oral care, and a dexamethasone-based mouthwash, whereas the control group received chemotherapy and oral care. The primary endpoint was the incidence of stomatitis. This was a phase 2 study, and the significance level for the analysis of the primary endpoint was set a priori at 0.2.
MAIN FINDINGS
Data pertaining to 58 patients in the control group and 59 patients in the intervention group were analyzed. Stomatitis incidence was 55% and 38% in the control and intervention groups, respectively (risk ratio, 0.68; 80% confidence interval, 0.52-0.88; P = .052). Stomatitis severity was lower in the intervention group than in the control group (P = .03). The proportion of patients who adhered to the mouthwash regimen was 87% (interquartile range, 67.8%-95.3%). No severe oral infections were observed.
PRINCIPAL CONCLUSIONS
The dexamethasone-based mouthwash safely reduced stomatitis incidence and severity in patients receiving chemotherapy for early breast cancer. Phase 3 clinical trials are warranted for validating our results.
Topics: Humans; Female; Mouthwashes; Breast Neoplasms; Stomatitis; Cyclophosphamide; Antineoplastic Agents; Dexamethasone
PubMed: 37689451
DOI: 10.1016/j.jebdp.2023.101896