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1.
CA Cancer J Clin ; 72(1): 57-77, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34714553

RESUMO

Oral mucositis (OM) is a common, highly symptomatic complication of cancer therapy that affects patients' function, quality of life, and ability to tolerate treatment. In certain patients with cancer, OM is associated with increased mortality. Research on the management of OM is ongoing. Oral mucosal toxicities are also reported in targeted and immune checkpoint inhibitor therapies. The objective of this article is to present current knowledge about the epidemiology, pathogenesis, assessment, risk prediction, and current and developing intervention strategies for OM and other ulcerative mucosal toxicities caused by both conventional and evolving forms of cancer therapy.


Assuntos
Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias/terapia , Úlceras Orais/epidemiologia , Lesões por Radiação/epidemiologia , Estomatite/epidemiologia , Humanos , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Mucosa Bucal/efeitos da radiação , Úlceras Orais/diagnóstico , Úlceras Orais/etiologia , Úlceras Orais/psicologia , Prevalência , Qualidade de Vida , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Lesões por Radiação/psicologia , Índice de Gravidade de Doença , Estomatite/diagnóstico , Estomatite/etiologia , Estomatite/psicologia
2.
FASEB J ; 38(19): e70102, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39382026

RESUMO

Intestinal mucositis (IM) is one of the most serious side effects of the chemotherapeutic agent irinotecan (CPT-11). Astragalus membranaceus-Pueraria lobata decoction is from the ancient medical book Zhengzhihuibu, has been reported to be used for the treatment of diabetes and hypertension. However, the beneficial effect and mechanism of AP on chemotherapy intestinal mucositis (CIM) remain largely unknown. This study aimed to investigate the efficacy and mechanism of Astragalus membranaceus-Pueraria lobata decoction (AP) in treating CIM. The beneficial effect and mechanism of AP on chemotherapy intestinal mucositis (CIM) were detected using Drosophila model, and combination with RT qPCR, transcriptomics. AP supplementation could significantly alleviate the CPT-11-induced body injury in Drosophila, such as increasing the survival rate, recovering the impaired digestion, improving the movement, and repairing the reproduction and developmental processes. Administration of AP remarkably alleviated the IM caused by CPT-11, including inhibiting the excretion, repairing the intestinal atrophy, improving the acid-base homeostasis imbalance, and inhibiting the disruption of intestinal structure. Mechanistic studies revealed that the protective role of AP against CPT-11 induced intestinal injury was regulated mainly by inhibiting immune-related Toll and Imd pathways, and enhancing the antioxidant capacity. Taken together, these results suggest that AP may be a novel agent to relieve CIM.


Assuntos
Astragalus propinquus , Irinotecano , Animais , Astragalus propinquus/química , Irinotecano/farmacologia , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Drosophila melanogaster/efeitos dos fármacos
3.
Int J Cancer ; 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39150399

RESUMO

Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C-reactive protein, CRP) in children with ALL during high-dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (n = 52) and the ALLTogether1 protocol (n = 42), both with identical HDMTX procedures but different scheduling. One week post-HDMTX, citrulline dropped to median levels of 14.5 and 16.9 µM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (p = 0.11). In a protocol and neutrophil count-adjusted analysis, hypocitrullinaemia (<10 µmol/L) was associated with increased odds of BSI within 3 weeks from HDMTX (OR = 26.2, p = 0.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal- and systemic inflammation post-HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7 pg/mL, p < 0.0001) and CRP levels (10.0 vs. 1.0 mg/L, p < 0.0001). Both citrulline and CCL20 correlated with CRP for these patients (rs = -0.44, p = 0.0016 and rs = 0.35, p = 0.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.

4.
Curr Issues Mol Biol ; 46(9): 10545-10569, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39329977

RESUMO

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.

5.
Cancer ; 130(1): 150-161, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37688396

RESUMO

BACKGROUND: This study investigated the influence of oral microbial features on the trajectory of oral mucositis (OM) in patients with squamous cell carcinoma of the head and neck. METHODS: OM severity was assessed and buccal swabs were collected at baseline, at the initiation of cancer treatment, weekly during cancer treatment, at the termination of cancer treatment, and after cancer treatment termination. The oral microbiome was characterized via the 16S ribosomal RNA V4 region with the Illumina platform. Latent class mixed-model analysis was used to group individuals with similar trajectories of OM severity. Locally estimated scatterplot smoothing was used to fit an average trend within each group and to assess the association between the longitudinal OM scores and longitudinal microbial abundances. RESULTS: Four latent groups (LGs) with differing patterns of OM severity were identified for 142 subjects. LG1 has an early onset of high OM scores. LGs 2 and 3 begin with relatively low OM scores until the eighth and 11th week, respectively. LG4 has generally flat OM scores. These LGs did not vary by treatment or clinical or demographic variables. Correlation analysis showed that the abundances of Bacteroidota, Proteobacteria, Bacteroidia, Gammaproteobacteria, Enterobacterales, Bacteroidales, Aerococcaceae, Prevotellaceae, Abiotrophia, and Prevotella_7 were positively correlated with OM severity across the four LGs. Negative correlation was observed with OM severity for a few microbial features: Abiotrophia and Aerococcaceae for LGs 2 and 3; Gammaproteobacteria and Proteobacteria for LGs 2, 3, and 4; and Enterobacterales for LGs 2 and 4. CONCLUSIONS: These findings suggest the potential to personalize treatment for OM. PLAIN LANGUAGE SUMMARY: Oral mucositis (OM) is a common and debilitating after effect for patients treated for squamous cell carcinoma of the head and neck. Trends in the abundance of specific microbial features may be associated with patterns of OM severity over time. Our findings suggest the potential to personalize treatment plans for OM via tailored microbiome interventions.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Microbiota , Estomatite , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/tratamento farmacológico
6.
Am J Physiol Gastrointest Liver Physiol ; 326(5): G504-G524, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38349111

RESUMO

Genotoxic agents such as doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mechanistic target of rapamycin complex 1 (mTORC1) in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fasting followed by refeeding at the time of DXR administration reduced damage and caused a spike in mTORC1 activity. However, continued fasting after DXR prevented the mTORC1 spike and damage reduction. Surprisingly, the mTORC1 inhibitor, rapamycin, did not block fasting/refeeding-induced reduction in DNA damage, suggesting that increased mTORC1 is dispensable for protection against the initial DNA damage response. In Ddit4-/- mice [DDIT4 (DNA-damage-inducible transcript 4) functions to regulate mTORC1 activity], fasting reduced DNA damage and increased intestinal crypt viability vs. ad libitum-fed Ddit4-/- mice. Fasted/refed Ddit4-/- mice maintained body weight, with increased crypt proliferation by 5 days post-DXR, whereas ad libitum-fed Ddit4-/- mice continued to lose weight and displayed limited crypt proliferation. Genes encoding epithelial stem cell and DNA repair proteins were elevated in DXR-injured, fasted vs. ad libitum Ddit4-/- intestines. Thus, fasting strongly reduced intestinal damage when normal dynamic regulation of mTORC1 was lost. Overall, the results confirm that fasting protects the intestines against DXR and suggests that fasting works by pleiotropic - including both mTORC1-dependent and independent - mechanisms across the temporally dynamic injury response.NEW & NOTEWORTHY New findings are 1) DNA damage reduction following a 24-h fast depends on the timing of postfast refeeding in relation to chemotherapy initiation; 2) fasting/refeeding-induced upregulation of mTORC1 activity is not required for early (6 h) protection against DXR-induced DNA damage; and 3) fasting increases expression of intestinal stem cell and DNA damage repair genes, even when mTORC1 is dysregulated, highlighting fasting's crucial role in regulating mTORC1-dependent and independent mechanisms in the dynamic recovery process.


Assuntos
Doxorrubicina , Intestino Delgado , Intestinos , Camundongos , Animais , Intestinos/fisiologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Adutos de DNA , Jejum/fisiologia
7.
Oncologist ; 29(3): e382-e391, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-37874927

RESUMO

OBJECTIVES: Immune-related adverse events (irAEs) are common. Oral irAEs tend to cluster in patients who experience concurrent toxicities. We aimed to characterize the frequency and trajectory of non-oral irAEs in patients who developed oral irAEs, assess their relationship with non-oral irAEs, and compare those characteristics with patients without oral irAEs. METHODS: A retrospective chart review was conducted to identify patients who started ICIT between December 11, 2011, and September 15, 2019 (n = 4683) in the Mass General Brigham Registered Patient Data Registry. Demographic information, cancer diagnosis, ICIT regimen, treatment duration, and time and number of infusions to irAE onset were recorded. Non-oral irAEs were categorized into 13 groups. Patients with melanoma, pulmonary cancer, or head and neck cancer who had oral irAEs were then matched with those without oral irAEs to compare the prevalence of concomitant non-oral irAEs. RESULTS: Three hundred and fourteen patients with oral irAEs with a mean age of 65.9 ±â€…12.6 years (43.3% females) were included. Patients with multiple oral irAEs were more likely to have non-oral irAEs (OR: 2.7, 95% CI, 1.3-3.5), including cutaneous (OR: 1.7, 95% CI, 1.1-3.0), rheumatological (OR: 2.2, 95% CI, 1.1-4.2), thyroid (OR: 2.4, 95% CI, 1.2-4.9), and neurological irAEs (OR: 2.5, 95% CI, 1.0-6.3). Compared to matched patients with non-oral irAEs, patients with oral irAEs were more likely to have cutaneous (OR: 1.7, 95% CI, 1.0-2.8) and thyroid (OR: 2.86, 95% CI, 1.1-7.5) irAEs. The development of oral and non-oral irAEs is often coincidental. CONCLUSION: Patients who have non-oral irAEs should be monitored for development of oral irAEs for prompt management.


Assuntos
Antineoplásicos Imunológicos , Neoplasias Pulmonares , Melanoma , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Nivolumabe/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Estudos Retrospectivos , Melanoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico
8.
J Transl Med ; 22(1): 863, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39334314

RESUMO

Radiation-induced oral mucositis (RIOM) is a prevalent oral complication that occurs in individuals undergoing radiotherapy or radiation treatment for head and neck tumors. The presence of oral mucosal rupture and ulcerative lesions, which are the defining features of this condition, can significantly affect the quality of life of patients. Additionally, it can interfere with tumor therapy and contribute to an unfavorable prognosis. Current evidence suggests that cellular inflammation and programmed cell death are important factors in disease development. Moreover, thalidomide (THD) has been revealed to reduce the incidence and severity of RIOM in patients undergoing chemoradiotherapy for nasopharyngeal carcinoma. However, the mechanism through which THD improves RIOM remains unknown. This study aimed to investigate the role of LZTS3 in RIOM by analyzing various sequencing datasets and conducting knockdown and overexpression experiments. We used small interfering RNA transfection and LZTS3 overexpression, followed by validation through polymerase chain reaction, western blotting, flow cytometry, and enzyme-linked immunosorbent assay. In this study, we identified LZTS3 as a potential target for THD regulation in RIOM. Through a series of experiments, we confirmed that LZTS3 has the ability to inhibit the inflammatory response and apoptosis of cells. In addition, we also found that THD can regulate the expression of LZTS3 by upregulating, thereby affecting inflammatory response and apoptosis. We repeated these results in a live animal model. In summary, THD has the potential to reduce the occurrence of oral mucositis in patients by upregulating LZTS3 levels. These findings provide a promising avenue for future drug research and development to treat RIOM.


Assuntos
Apoptose , Citocinas , Células Epiteliais , Talidomida , Apoptose/efeitos dos fármacos , Talidomida/farmacologia , Talidomida/uso terapêutico , Humanos , Células Epiteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/efeitos da radiação , Citocinas/metabolismo , Animais , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/patologia , Mucosa Bucal/efeitos da radiação , Mucosa Bucal/metabolismo , Estomatite/metabolismo , Estomatite/patologia , Estomatite/etiologia , Estomatite/prevenção & controle , Mediadores da Inflamação/metabolismo , Camundongos , Inflamação/patologia
9.
Microb Pathog ; 193: 106785, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38971507

RESUMO

OBJECTIVES: To assess the effect of probiotics in oral mucositis induced by chemotherapy or radiotherapy on patients with head and neck cancer (HNC). METHODS: The PubMed, Embase, Cochrane Library, Clinical trials were screened from January 2010 to April 2024. Randomized clinical trials (RCTs) comparing the efficacy of probiotics in treatment of oral mucositis in HNC were eligible. Outcomes of interest were incidence of oral mucositis and severe oral mucositis. The PROSPERO registration number was 42 022 384 685. The Cochrane risk-of-bias tool (RoB2) was used to assess methodological quality of studies and GRADE criteria (GRADEpro) was applied for rating the certainty of evidence. Meta-analysis was performed by using RevMan 5.4. RESULTS: A total of eight RCTs comprising 691 patients with HNC were included in this meta-analysis. Probiotics administration significantly reduced the incidence of SOM (RR = 0.60, 95%CI: 0.46-0.78, P = 0.0002). However, it showed no distinct advantage in reducing the overall incidence of oral mucositis (RR = 0.88, 95%CI: 0.76-1.02, P = 0.08). Subgroup analysis found more benefit for reducing SOM in multi-bacterial treated group (RR = 0.35, 95%CI: 0.17-0.73, P = 0.005) than mono-bacterial treated group (RR = 0.69, 95%CI: 0.58-0.82, P < 0.0001). In Addition, probiotics could reduce the incidence of SOM in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (RR = 0.43, 95%CI: 0.26-0.70, P = 0.0006). CONCLUSION: Probiotics reduced the incidence of SOM caused by chemotherapy or radiotherapy for HNC. The multi-bacterial combination therapy was more efficacious than the mono-bacterial therapy. Moreover, probiotics also reduced the incidence of SOM in nasopharyngeal carcinoma. However, the advantage of probiotics had not been established in the overall incidence of OM.


Assuntos
Neoplasias de Cabeça e Pescoço , Probióticos , Estomatite , Probióticos/uso terapêutico , Humanos , Estomatite/prevenção & controle , Estomatite/etiologia , Estomatite/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Incidência
10.
Scand J Immunol ; 100(4): e13399, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39073054

RESUMO

Oral mucositis (OM) is a severe side effect of anti-cancer therapy, with limited available treatments. Mesenchymal stem cells (MSCs) and their secreted extracellular vesicles (EVs) have demonstrated effective protection against OM. However, the underlying mechanism remains elusive. In the current study, we purified EVs secreted by human umbilical cord MSCs (hUC-MSC-EVs) and investigated their role in lipopolysaccharide (LPS)-induced human oral keratinocytes (HOKs). We observed that treatment with hUC-MSC-EVs significantly reduced the inflammatory response of HOKs to LPS induction. Through small RNA-seq using miRNAs extracted from hUC-MSC-EVs, we identified hsa-let-7e-5p as one of the most highly expressed miRNAs. Bioinformatic analysis data indicated that hsa-let-7e-5p may inhibit the NF-κB signalling pathway by targeting TAB2. Overexpression of the hsa-let-7e-5p inhibitor significantly attenuated the anti-inflammatory effect of hUC-MSC-EVs in LPS-induced HOKs, which could be reversed by the knockdown of TAB2. In addition, we administered hUC-MSC-EVs in a hamster model for OM and observed that these EVs alleviated OM phenotypes. Taken together, our observations suggest that hsa-let-7e-5p in hUC-MSC-EVs could protect the oral mucosa from OM by repressing TAB2 expression.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Vesículas Extracelulares , Queratinócitos , Lipopolissacarídeos , Células-Tronco Mesenquimais , MicroRNAs , Estomatite , MicroRNAs/genética , Humanos , Estomatite/metabolismo , Estomatite/terapia , Animais , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Cricetinae , Modelos Animais de Doenças , Cordão Umbilical/citologia , Mucosa Bucal/metabolismo , Células Cultivadas
11.
Strahlenther Onkol ; 200(7): 583-594, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38381142

RESUMO

BACKGROUND AND OBJECTIVE: Data on enteral tube feeding in head and neck cancer (HNC) patients undergoing chemoradiotherapy vary considerably between German institutions. This survey aims to investigate the management of feeding tubes in an interdisciplinary context across Germany. MATERIALS AND METHODS: Between December 2022 and May 2023, 70 participants (42 radiation oncologists, 12 medical oncologists, 14 head and neck surgeons, and 2 physicians covering several specialties) responded to our web-based survey. In addition to the type of institution (university hospital, private practice, etc.), their age, and professional experience (in years), participants were asked several questions on the indication and institutional policy for tube placement and management (prophylactic/reactive nasogastric or gastrostomy tube). All questions were mandatory single- or multiple-choice questions, while additional comments were possible by email. RESULTS: Most participants were employed at a university hospital (n = 52; 74.3%) and came from a radiation oncology background (n = 42; 60%). Fifty-four contributors (77.1%) reported that no nutritional risk screening prior to chemoradiotherapy was routinely performed, and 71.4% (n = 50) stated that no standardized protocol was used at the institution to set the indication for tube placement. Generally, policies and methods of tube feeding vary considerably between the individual institutions and specialties. However, the majority (n = 56, 80%) recommended a prophylactic percutaneous enteral gastrostomy (PEG) tube to their patients before chemoradiotherapy. Still, there was no consistent trend regarding the approach for reactive tube feeding. CONCLUSION: The policies and methods of tube feeding vary considerably between the individual institutions and specialties in Germany. In the era of individualized medicine, uniform protocols are difficult to establish. However, a baseline nutritional risk screening could simplify decision-making in clinical practice.


Assuntos
Quimiorradioterapia , Nutrição Enteral , Gastrostomia , Neoplasias de Cabeça e Pescoço , Intubação Gastrointestinal , Humanos , Alemanha , Neoplasias de Cabeça e Pescoço/terapia , Masculino , Inquéritos e Questionários , Padrões de Prática Médica/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde , Comunicação Interdisciplinar , Pessoa de Meia-Idade , Radio-Oncologistas
12.
Strahlenther Onkol ; 200(10): 895-902, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38926185

RESUMO

OBJECTIVES: To assess the predictive value of different dosimetric parameters for acute radiation oral mucositis (ROM) in head and neck cancer (HNCs) patients treated with carbon-ion radiotherapy (CIRT). METHODS: 44 patients with HNCs treated with CIRT were evaluated for acute ROM which was defined as severe when the score ≥3 (acute ROM was scored prospectively using the Radiation Therapy Oncology Group (RTOG) score system). Predictive dosimetric factors were identified by using univariate and multivariate analysis. RESULTS: Male gender, weight loss >5%, and total dose/fractions were related factors to severe ROM. In multivariate analysis, grade ≥3 ROM was significantly related to the Dmax, D10, D15, and D20 (P < 0.05, respectively). As the receiver operating characteristics (ROC) curve shows, the area under the curve (AUC) for D10 was 0.77 (p = 0.003), and the cutoff value was 51.06 Gy (RBE); The AUC for D15 was 0.75 (p = 0.006), and the cutoff value was 42.82 Gy (RBE); The AUC for D20 was 0.74 (p = 0.009), and the cutoff value was 30.45 Gy (RBE); The AUC for Dmax was 0.81 (p < 0.001), and the cutoff value was 69.33 Gy (RBE). CONCLUSION: Male gender, weight loss, and total dose/fractions were significantly association with ROM. Dmax, D10, D15 and D20 were identified as the most valuable predictor and we suggest a Dmax limit of 69.33 Gy (RBE), D10 limit of 51.06 Gy (RBE), D15 limit of 42.82 Gy (RBE), and D20 limit of 30.45 Gy (RBE) and for oral mucosa.


Assuntos
Radioterapia com Íons Pesados , Lesões por Radiação , Dosagem Radioterapêutica , Estomatite , Humanos , Masculino , Feminino , Estomatite/etiologia , Estomatite/radioterapia , Pessoa de Meia-Idade , Idoso , Radioterapia com Íons Pesados/efeitos adversos , Lesões por Radiação/etiologia , Adulto , Neoplasias de Cabeça e Pescoço/radioterapia , Idoso de 80 Anos ou mais , Doença Aguda , Redução de Peso/efeitos da radiação , Resultado do Tratamento , Fatores de Risco
13.
Inflamm Res ; 73(10): 1781-1801, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39180691

RESUMO

OBJECTIVE: Intestinal mucositis is one of the common side effects of anti-cancer chemotherapy. However, the molecular mechanisms involved in mucositis development remain incompletely understood. In this study, we investigated the function of receptor-interacting protein kinase 3 (RIP3/RIPK3) in regulating doxorubicin-induced intestinal mucositis and its potential mechanisms. METHODS: Intestinal mucositis animal models were induced in mice for in vivo studies. Rat intestinal cell line IEC-6 was used for in vitro studies. RNA­seq was used to explore the transcriptomic changes in doxorubicin-induced intestinal mucositis. Intact glycopeptide characterization using mass spectrometry was applied to identify α-1,2-fucosylated proteins associated with mucositis. RESULTS: Doxorubicin treatment increased RIP3 expression in the intestine and caused severe intestinal mucositis in the mice, depletion of RIP3 abolished doxorubicin-induced intestinal mucositis. RIP3-mediated doxorubicin-induced mucositis did not depend on mixed lineage kinase domain-like (MLKL) but on α-1,2-fucosyltransferase 2 (FUT2)-catalyzed α-1,2-fucosylation on inflammation-related proteins. Deficiency of MLKL did not affect intestinal mucositis, whereas inhibition of α-1,2-fucosylation by 2-deoxy-D-galactose (2dGal) profoundly attenuated doxorubicin-induced inflammation and mucositis. CONCLUSIONS: RIP3-FUT2 pathway is a central node in doxorubicin-induced intestinal mucositis. Targeting intestinal RIP3 and/or FUT2-mediated α-1,2-fucosylation may provide potential targets for preventing chemotherapy-induced intestinal mucositis.


Assuntos
Doxorrubicina , Fucosiltransferases , Galactosídeo 2-alfa-L-Fucosiltransferase , Camundongos Endogâmicos C57BL , Mucosite , Proteína Serina-Treonina Quinases de Interação com Receptores , Animais , Doxorrubicina/efeitos adversos , Mucosite/induzido quimicamente , Mucosite/metabolismo , Mucosite/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Fucosiltransferases/genética , Fucosiltransferases/metabolismo , Ratos , Linhagem Celular , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Masculino , Camundongos , Antibióticos Antineoplásicos/toxicidade , Antibióticos Antineoplásicos/efeitos adversos , Camundongos Knockout
14.
Pediatr Blood Cancer ; 71(6): e30966, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38556719

RESUMO

BACKGROUND: Oral mucositis (OM) is a painful and common complication of hematopoietic stem cell transplant (HSCT). The Children's Oncology Group recently published guidelines recommending photobiomodulation (PBM) for preventing and treating OM in pediatric HSCT patients. However, this is a rarely used intervention in pediatric hospitals. PROCEDURE: Patients undergoing allogeneic HSCT, or autologous HSCT for a neuroblastoma diagnosis, had PBM administered from the first day of conditioning to transplant Day +20. We successfully developed a standardized treatment protocol and workflow to ensure consistent and uniform delivery of PBM. In addition, clinical patient data were compared before and after PBM implementation. RESULTS: The administration of PBM at our center was feasible, but required dedicated staff. A registered nurse (RN) was determined to be the best fit to deliver PBM. Sixty-two patients received PBM from October 2022 to September 2023; patients from 2021 before PBM implementation were used for comparison. Patients receiving PBM were more likely (p = .03) to engage in teeth brushing (56/62 = 90%) compared to baseline (61/81 = 75%). Mean days of OM decreased from 11.3 to 9 days; patients who received PBM were less likely (p < .001) to be discharged on total parental nutrition (TPN) (11/62 = 18%) compared to baseline (50/82 = 61%). OM-related supportive care costs (TPN and patient-controlled anesthesia [PCA]) were lower (p = .02) for those who received PBM (median cost = $31,229.87 vs. $37,370.66). CONCLUSION: PBM, as the standard of care in the pediatric HSCT population, is safe, feasible, and well-tolerated. At our center, a dedicated RN was critical to providing standardized treatment and ensuring sustainability.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Terapia com Luz de Baixa Intensidade , Estomatite , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estomatite/etiologia , Estomatite/prevenção & controle , Estomatite/terapia , Criança , Masculino , Feminino , Terapia com Luz de Baixa Intensidade/métodos , Pré-Escolar , Adolescente , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Lactente , Seguimentos , Prognóstico
15.
Pediatr Blood Cancer ; : e31388, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39420503

RESUMO

Oral mucositis (OM) is a prevalent acute adverse effect of various cancer treatments. Accurate assessment of OM is vital for effective prevention and treatment strategies. However, a lack of validated pediatric instruments for evaluating OM can lead to unreliable data, and hinder interventional and epidemiological research. This study aims to evaluate the methods used for assessing OM in pediatric oncology patients. A systematic review of four databases and a manual search yielded 113 articles. Nine different scales were identified, with the World Health Organization (WHO) scale being the most commonly used (61.9%). The Children's International Mucositis Evaluation Scale (ChIMES) was used in 7.9% of the studies. Of the 8155 pediatric patients evaluated, 47.7% had both hematological malignancies and malignant solid tumors, while 46% had solely hematological malignancies. Despite the prevalence of the WHO scale, it lacks pediatric-specific criteria. Future OM research should incorporate validated tools like ChIMES for improved pediatric assessment.

16.
J Am Acad Dermatol ; 91(5): 805-815, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38307144

RESUMO

Photobiomodulation (PBM) is an emerging treatment modality in dermatology with increasing office and home-based use. PBM is the use of various light sources in the red light (620-700 nm) and near-infrared (700-1440 nm) spectrum as a form of light therapy. PBM is often administered through low-level lasers or light-emitting diodes. Studies show that PBM can be used effectively to treat conditions secondary to cancer therapies, alopecia, ulcers, herpes simplex virus, acne, skin rejuvenation, wounds, and scars. PBM offers patients many benefits compared to other treatments. It is noninvasive, cost-effective, convenient for patients, and offers a favorable safety profile. PBM can be used as an alternative or adjuvant to other treatment modalities including pharmacotherapy. It is important for dermatologists to gain a better clinical understanding of PBM for in-office administration and to counsel patients on proper application for home-use devices to best manage safety and expectations as this technology develops. PBM wavelengths can induce varied biological effects in diverse skin types, races, and ethnicities; therefore, it is also important for dermatologists to properly counsel their skin of color patients who undergo PBM treatments. Future clinical trials are necessary to produce standardized recommendations across conditions and skin types.


Assuntos
Dermatologia , Terapia com Luz de Baixa Intensidade , Dermatopatias , Humanos , Terapia com Luz de Baixa Intensidade/métodos , Terapia com Luz de Baixa Intensidade/efeitos adversos , Terapia com Luz de Baixa Intensidade/instrumentação , Dermatopatias/radioterapia , Dermatopatias/terapia , Dermatologia/métodos , Rejuvenescimento , Envelhecimento da Pele/efeitos da radiação , Alopecia/radioterapia , Alopecia/terapia , Acne Vulgar/radioterapia , Acne Vulgar/terapia , Cicatriz/radioterapia , Cicatriz/terapia , Cicatriz/etiologia
17.
Curr Oncol Rep ; 26(4): 391-399, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38502418

RESUMO

PURPOSE OF REVIEW: It is recognized that patients undergoing cancer treatment experience different adverse effects depending on the type of therapy they received. The objective of this work is to provide a scientific evidence-based protocol for oral care in cancer patients. Cancer resection surgery, chemotherapy, and radiotherapy can cause important complications that impact patients' quality of life. RECENT FINDINGS: Cancer patients, from the moment of diagnosis to the end of treatment and subsequent follow-up, have diverse care needs, both from a systemic and local point of view. The implementation of oral care protocols before, during, and after cancer therapy is essential because it helps to identify risk factors for the development of predictable oral complications. It is essential to establish that all cancer patients, before starting treatment, undergo a systematic dental check-up to avoid limitations during treatment and also alter their quality of life. Regular professional oral care maintenance and follow-up programs are essential to maintaining a patient's long-term oral health.


Assuntos
Neoplasias , Estomatite , Humanos , Estomatite/etiologia , Estomatite/terapia , Qualidade de Vida , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Oncologia , Odontologia
18.
Pediatr Transplant ; 28(5): e14820, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38977381

RESUMO

BACKGROUND: There is a lack of studies analyzing the association between oral mucositis (OM) and nutritional imbalance in children during hematopoietic stem cell transplantation (HSCT). The aim of this study was to compare the risk factors for OM and nutritional imbalance during HSCT in pediatric patients with nonmalignant diseases (NMD) and malignant diseases (MD). METHODS: Data on age, sex, primary disease, transplantation type, conditioning regimen, GVHD prophylaxis, gastrointestinal toxicity, OM, percent body weight loss or gain, nutritional repositioning, and overall survival (OS) were retrospectively collected from the 132 medical records. The data were then compared between patients with NMD (n = 70) and MD (n = 62). RESULTS: OM had a similar severity between the groups. The primary risk factor for OM in the NMD group was the conditioning regimen with busulfan, while in the MD group it was GVHD prophylaxis with cyclosporin and methotrexate. OM did not have an impact on body weight loss or gain in any of the groups. In the NMD, body weight gain due to fluid overload was more pronounced and associated with a lower age range. OS was similar between the groups and was not affected by OM. CONCLUSIONS: OM pattern was similar in pediatric patients with or without MD, but the factors that determined these oral lesions were different. There were disparities in body weight changes between the two groups, and these changes were not associated to OM.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Estado Nutricional , Estomatite , Condicionamento Pré-Transplante , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Feminino , Masculino , Criança , Pré-Escolar , Estomatite/etiologia , Estudos Retrospectivos , Adolescente , Lactente , Condicionamento Pré-Transplante/métodos , Condicionamento Pré-Transplante/efeitos adversos , Fatores de Risco , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias/complicações
19.
Biomed Eng Online ; 23(1): 101, 2024 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-39396020

RESUMO

Peri-implantitis (PI), a pathological condition associated with plaque, affects the tissues around dental implants. In addition, peri-implant mucositis (PIM) is a precursor to the destructive inflammatory PI and is an inflammation of the soft tissues surrounding the dental implant. It is challenging to eradicate and regulate the PI treatment due to its limited effectiveness. Currently, there is a significant interest in the development and research of additional biocompatible materials to prevent the failure of dental implants. Nanotechnology has the potential to address or develop solutions to the significant challenge of implant failure caused by cytotoxicity and biocompatibility in dentistry. Nanoparticles (NPs) may be used as carriers for the release of medicines, as well as to make implant coatings and supply appropriate materials for implant construction. Furthermore, the bioactivity and therapeutic efficacy of metal NPs in peri-implant diseases (PID) are substantiated by a plethora of in vitro and in vivo studies. Furthermore, the use of silver (Ag), gold (Au), zinc oxide, titanium oxide (TiO2), copper (Cu), and iron oxide NPs as a cure for dental implant infections brought on by bacteria that have become resistant to several medications is the subject of recent dentistry research. Because of their unique shape-dependent features, which enhance bio-physio-chemical functionalization, antibacterial activity, and biocompatibility, metal NPs are employed in dental implants. This study attempted to provide an overview of the application of metal and metal oxide NPs to control and increase the success rate of implants while focusing on the antimicrobial properties of these NPs in the treatment of PID, including PIM and PI. Additionally, the study reviewed the potential benefits and drawbacks of using metal NPs in clinical settings for managing PID, with the goal of advancing future treatment strategies for these conditions.


Assuntos
Implantes Dentários , Nanopartículas Metálicas , Peri-Implantite , Peri-Implantite/tratamento farmacológico , Peri-Implantite/terapia , Nanopartículas Metálicas/química , Humanos , Implantes Dentários/efeitos adversos , Animais , Mucosite/tratamento farmacológico , Estomatite/tratamento farmacológico , Estomatite/etiologia
20.
Support Care Cancer ; 32(9): 597, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162830

RESUMO

OBJECTIVES: This study aimed to evaluate the severity of oral mucositis and the contributing factors among cancer patients undergoing chemotherapy. METHODS: This study was planned cross-sectional. The study was conducted at a medical oncology clinic between January and July 2022. The sample consisted of 245 patients with cancer receiving chemotherapy. Data were collected using a personal, oral health and disease-related characteristics questionnaire and the World Health Organization Oral Mucositis Assessment Scale by researchers. Intraoral examination of the patients was carried out by researchers. The data were analyzed by independent-sample t-tests, Chi-square tests, paired-sample t-tests, and multivariate logistic regression (p < 0,05). RESULTS: The patients had mean age 62.31 ± 10.70. Patients of 32.7% were with lung cancer. 52%of the patients (n = 128) receiving chemotherapy developed oral mucositis. The independent variables the presence chronic disease(OR:1.85), chemotherapy protocol (OR:3.52) and the dependent variables ECOG performance score (OR:2.25) were variable that affected the development of oral mucositis (p < 0.05). Patients of 35.5% were oral mucositis score of 1. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis (p < 0.05). In addition, oral mucositis was more prevalent in patients with chronic diseases other than cancer (57%), those who used medication continuously (57.2%), those with oral and dental diseases (56.9%), those who had dental check-ups before cancer treatment (79.2%), and those who had information about oral mucositis(70.2%) (p < 0.05). CONCLUSION: In conclusion, nearly half of the patients (52%, n = 128) receiving chemotherapy developed oral mucositis and of all patients of 35.5% had an oral mucositis score of 1 in the second round of chemotherapy. Patients those who had breast cancer, who received doxorubicin or cyclophosphamide chemotherapy protocols, and who had previously developed oral mucositis were found to have a higher rate of oral mucositis.


Assuntos
Antineoplásicos , Neoplasias , Estomatite , Humanos , Estomatite/induzido quimicamente , Estomatite/epidemiologia , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Idoso , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Antineoplásicos/efeitos adversos , Inquéritos e Questionários , Índice de Gravidade de Doença , Fatores de Risco , Adulto , Modelos Logísticos
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