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Annals of Oncology : Official Journal... Dec 2019Alterations in the phosphoinositide 3-kinase (PI3K)/AKT pathway are frequently found in cancer and are especially common in breast cancer, where it is estimated that 70%... (Review)
Review
Alterations in the phosphoinositide 3-kinase (PI3K)/AKT pathway are frequently found in cancer and are especially common in breast cancer, where it is estimated that 70% of tumors have some type of genetic alteration that could lead to pathway hyperactivation. A variety of PI3K pathway inhibitors have been developed in an attempt to target this pathway and improve cancer control. One of the challenges in treating patients with PI3K/AKT pathway inhibitors is the associated toxicity from on-target and off-target effects. Such side-effects are common, but reversible, and include hyperglycemia, rash, stomatitis, diarrhea, nausea, and fatigue. As a result, dose reductions, treatment delays, and treatment discontinuation are frequently reported. This impairs not only patients' quality of life but also treatment efficacy. Most side-effects are reversible with drug interruption, since these drugs typically have a short half-life and are manageable with early intervention. An interdisciplinary approach with proactive management of patients receiving PI3K pathway inhibitors should include comprehensive education of patients about the range of toxicities, frequent monitoring, early toxicity recognition, active intervention, as well as prophylactic strategies.
Topics: Breast Neoplasms; Diarrhea; Fatigue; Female; Humans; Hyperglycemia; Palliative Care; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Signal Transduction; Stomatitis
PubMed: 31626273
DOI: 10.1093/annonc/mdz440 -
The Journal of Allergy and Clinical... Jun 2023Children and adults with autoinflammatory disorders, who often experience recurrent fevers, rashes, cold-induced symptoms, conjunctivitis, lymphadenopathy, recurrent...
Children and adults with autoinflammatory disorders, who often experience recurrent fevers, rashes, cold-induced symptoms, conjunctivitis, lymphadenopathy, recurrent infections, aphthous stomatitis, and abnormal blood cell counts, may present to the allergist/immunologist because the symptoms mimic allergies and disorders of immunity. In recent years, there has been increased recognition of non-monogenic autoinflammatory disorders, including periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome and syndrome of undifferentiated recurrent fevers. For many clinical practitioners, the natural history, diagnostic criteria, differential diagnoses, and preferred therapies remain challenging because of the presumed rarity of patients and the evolving field of autoinflammation. Here, we aim to provide a practical framework for the clinical allergist/immunologist to evaluate and treat this patient population.
Topics: Humans; Child; Adult; Stomatitis, Aphthous; Lymphadenitis; Pharyngitis; Fever; Lymphadenopathy; Nasopharyngitis; Syndrome
PubMed: 36958521
DOI: 10.1016/j.jaip.2023.03.014 -
Stomatologija 2023To analyze the latest systemic and topical recurrent aphthous stomatitis (RAS) treatment methods that could help patients in their daily lives.
AIM
To analyze the latest systemic and topical recurrent aphthous stomatitis (RAS) treatment methods that could help patients in their daily lives.
MATERIAL AND METHODS
A systematic literature review was performed of randomized control trials in English identified in MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (Cochrane Library), Researchgate, published between 2018 and 2023. Studies had to be performed in vivo.
RESULTS
34 randomized clinical trials matched all criterias and were included in systematic literature review. A wide variety of topical and systemic agents are suggested for the treatment of RAS.
CONCLUSION
Topical medications can promote the healing time of ulcers and relieve the pain, but most of the time can not decrease the frequency of RAS relapse. However, for continuous RAS, treatment with systemic medication should be considered.
Topics: Humans; Stomatitis, Aphthous; Pain; Recurrence
PubMed: 37436177
DOI: No ID Found -
Clinical and Experimental Dermatology Jan 2021
Topics: COVID-19; Humans; Male; Middle Aged; Stomatitis, Herpetic
PubMed: 33405295
DOI: 10.1111/ced.14402 -
Frontiers in Immunology 2023Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most frequent periodic fever syndrome in children. Its pathogenesis is still... (Clinical Trial)
Clinical Trial
INTRODUCTION
Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most frequent periodic fever syndrome in children. Its pathogenesis is still unknown, but some disease-modifying factors were observed. Several medications were tested for the long-term prophylaxis of inflammatory flares; however, none are standardly used.
METHODS
This prospective clinical trial enrolled 142 children (71 girls, 50%) meeting diagnostic criteria for PFAPA syndrome. We analysed selected clinical characteristics and compared laboratory parameters during the flare and attack-free period (at least two weeks after the attack). Moreover, we assessed the possible therapeutic effect of ketotifen on the duration of attack free-periods and clinical picture.
RESULTS
The mean age of patients was 6.81 ± 3.03 years and the mean age of onset of symptoms was 2.31 ± 2.02 years. No significant differences were observed between genders.We recorded a positive family history for PFAPA in 31.69% of patients. Attacks lasted for 2.8 ± 1.2 days, with intervals between attacks of 4 ± 1 weeks. We administered ketotifen in 111 (77.8%) patients, and a positive effect was observed in 86 (77.5%) of patients. We observed prolonged attack-free intervals in patients treated with ketotifen (14.7 ± 8.9 days in comparison with 4.4 ± 1.9 days before the treatment; p<0.001). The used dose of ketotifen was 0.08 ± 0.01 mg/kg/day. Mild side effects were observed in four patients (restlessness, irritability, agitation and constipation).
DISCUSSION
Our data supports the use of ketotifen for long-term prophylaxis in children with PFAPA syndrome with positive effects on the attenuation of disease activity and the prolongation of attack-free periods. Further well-designed studies should confirm the preliminary data.
Topics: Child; Humans; Male; Female; Child, Preschool; Infant; Ketotifen; Stomatitis, Aphthous; Pharyngitis; Lymphadenitis; Lymphadenopathy; Syndrome; Anti-Inflammatory Agents
PubMed: 38143757
DOI: 10.3389/fimmu.2023.1302875 -
Biomolecules Aug 2023Reactive oxygen species (ROS) are highly reactive molecules generated in living organisms and an excessive production of ROS culminates in oxidative stress and cellular...
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 (HO) 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, < 0.01), H357 cells (53.48 ± 4.01, < 0.01), and OKF6 cells (48.64 ± 3.09, < 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.
Topics: Humans; Animals; Mice; Mucositis; Reactive Oxygen Species; Hydrogen Peroxide; Reproducibility of Results; Oxidative Stress; Stomatitis; Disease Models, Animal; Drug-Related Side Effects and Adverse Reactions; Fluorescent Dyes
PubMed: 37627304
DOI: 10.3390/biom13081239 -
Supportive care and antiviral treatments in primary herpetic gingivostomatitis: a systematic review.Clinical Oral Investigations Nov 2023Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic... (Review)
Review
OBJECTIVES
Herpes simplex virus 1 (HSV-1) is the main pathogen responsible for herpes infections. In 13-30% of the cases, primary HSV-1 leads to the primary herpetic gingivostomatitis (PHGS), often a self-limiting infection; however, it can limit the ability to drink/eat with, sometimes, the need for hospitalization. Multiple therapeutic methods have been proposed. This systematic review aims to collect and critically appraise the available evidence about the clinical management of PHGS.
MATERIALS AND METHODS
Literature search including three databases (PubMed, Scopus, Embase), study design, and data analysis were performed following PRISMA guidelines, according to the PICO tool (PROSPERO n° CRD42023391386). Risk of bias was assessed with RoB 2 and ROBINS-I.
RESULTS
Five studies on a total of 364 patients (average age: 7.6 years) were identified. The treatment regimens were summarized in acyclovir; acyclovir + honey; fluids and analgesic; maalox + diphenhydramine; lidocaine; chlorhexidine (CHX); CHX + ialuronic acid; CHX + Mucosyte®; antimicrobial photodynamic therapy (aPDT); topical antiviral; topical antiviral + aPDT; and others.
CONCLUSIONS
Although PHGS is a disease with a high worldwide prevalence, the lack of consensus about therapeutic management indicates gaps in existing evidence. Most of the proposed treatment consists in symptomatic drugs with empiric regimens which are ineffective for the viral replication. The main limit to realize randomized clinical trial is due to the rapid onset and remission of the disease. In fact, the diagnostic delay, estimated in 72 h, decreases the effectiveness of any antiviral drugs.
CLINICAL RELEVANCE
Out of the five studies included in this systematic review, only one was able to provide some weak evidence that ACV is an effective treatment, improving healing of oral lesions and reducing duration of symptoms.
Topics: Humans; Child; Stomatitis, Herpetic; Delayed Diagnosis; Antiviral Agents; Acyclovir; Lidocaine; Randomized Controlled Trials as Topic
PubMed: 37733027
DOI: 10.1007/s00784-023-05250-5 -
Medicina Oral, Patologia Oral Y Cirugia... Sep 2022Oral mucositis (OM) is an important acute adverse effect of anticancer therapy. This condition presents high morbidity and may lead to the suspension of anticancer... (Review)
Review
BACKGROUND
Oral mucositis (OM) is an important acute adverse effect of anticancer therapy. This condition presents high morbidity and may lead to the suspension of anticancer therapy.
MATERIAL AND METHODS
We reviewed the literature on the pathobiology of OM and the properties of erythromycin (EM), to consider the possibility of its use for the prevention and treatment of OM. We searched the PubMed, Scopus and Web of Science databases and selected complete articles published in English or Spanish that met the inclusion criteria. The search terms "erythromycin", "inflammation", "immunomodulation" and "oral mucositis" were used.
RESULTS
The control of free radicals, transcription factors and pro-inflammatory cytokines has been considered as the key to the management of OM. EM has the ability to modulate oxidative stress, acts on the transcriptional system and inhibits the production of several cytokines that have been directly implicated in OM pathobiology.
CONCLUSIONS
The present review suggests that EM could be effective in the treatment of OM. Experimental studies investigating the use of EM in OM should be encouraged.
Topics: Cytokines; Erythromycin; Humans; Mucositis; Stomatitis
PubMed: 35717620
DOI: 10.4317/medoral.25439 -
International Journal of Molecular... Apr 2022With the development of psychology and medicine, more and more diseases have found their psychological origins and associations, especially ulceration and other mucosal... (Review)
Review
With the development of psychology and medicine, more and more diseases have found their psychological origins and associations, especially ulceration and other mucosal injuries, within the digestive system. However, the association of psychological factors with lesions of the oral mucosa, including oral squamous cell carcinoma (OSCC), burning mouth syndrome (BMS), and recurrent aphthous stomatitis (RAS), have not been fully characterized. In this review, after introducing the association between psychological and nervous factors and diseases, we provide detailed descriptions of the psychology and nerve fibers involved in the pathology of OSCC, BMS, and RAS, pointing out the underlying mechanisms and suggesting the clinical indications.
Topics: Carcinoma, Squamous Cell; Humans; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Stomatitis, Aphthous
PubMed: 35563151
DOI: 10.3390/ijms23094760 -
Cancer Treatment and Research... 2023Radiation-induced oral mucositis (RIOM) is one of the common toxic reactions from ionizing radiation and normal tissue injuries as a complication of radiation therapy... (Review)
Review
Radiation-induced oral mucositis (RIOM) is one of the common toxic reactions from ionizing radiation and normal tissue injuries as a complication of radiation therapy and chemotherapy. Radiation therapy is an option for the treatment of head and neck cancer (HNC). The use of natural products is an alternative therapy for RIOM. This review aimed to describe the effectiveness of natural-based products (NBPs) in reducing the severity, pain score, incidence, oral lesion size, and other symptoms such as dysphagia, dysarthria, and odynophagia. This systematic review follows the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Pubmed, ScienceDirect, and Ebscohost-CINAHL Plus databases were used for article searches. The inclusion criteria were studies published from 2012 to 2022 with full text available, in English, a study in humans, and a Randomized Clinical Trial (RCT) that evaluate the effect of NBPs therapy in RIOM patients diagnosed with HNC. This study's population was HNC patients who had oral mucositis after receiving radiation or chemical therapy. The NBPs were manuka honey, thyme honey, aloe vera, calendula, zataria multiflora, Plantago major L., and turmeric. Eight of the twelve included articles showed significant effectiveness against RIOM in various parameters, such as a decrease in severity, incidence rate, pain score, oral lesion size, and the other symptoms of oral mucositis such as dysphagia and burning mouth syndrome. This review concludes that NBPs therapy is effective for RIOM in HNC patients.
Topics: Humans; Deglutition Disorders; Head and Neck Neoplasms; Radiation Injuries; Randomized Controlled Trials as Topic; Stomatitis
PubMed: 37209466
DOI: 10.1016/j.ctarc.2023.100720