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Journal of Oral Pathology & Medicine :... Nov 2023Apoptosis resistance of myofibroblasts is critical in pathology of irradiation-induced fibrosis and osteoradionecrosis of the jaw (ORNJ). However, molecular mechanism of...
BACKGROUND
Apoptosis resistance of myofibroblasts is critical in pathology of irradiation-induced fibrosis and osteoradionecrosis of the jaw (ORNJ). However, molecular mechanism of apoptosis resistance induced by irradiation in oral myofibroblasts remains largely obscure.
METHODS
Matched ORNJ fibroblasts and normal fibroblasts pairs from gingival were primarily cultured, and myofibroblast markers of α-SMA and FAP were evaluated by qRT-PCR and western blot. CCK8 assay and flow cytometric analysis were performed to investigate the cell viability and apoptosis under irradiation treatment. Autophagy-related protein LC3 and ATG7, and punctate distribution of LC3 localization were further detected. After inhibition of autophagy with inhibitor CQ and 3-MA, as well as transfected ATG7-siRNA, cell viability and apoptosis of ORNJ and normal fibroblasts were further assessed.
RESULTS
Compared with normal fibroblasts, ORNJ fibroblasts exhibited significantly higher α-SMA and FAP expression, increased cell, viability and decreased apoptosis under irradiation treatment. LC3-II and ATG7 were up-regulated in ORNJ fibroblasts with irradiation stimulation. After inhibition of irradiation-induced autophagic flux with lysosome inhibitor CQ, LC3-II protein was accumulated and punctate distribution of LC3 localization was increased in ORNJ fibroblasts. Moreover, autophagy inhibitor CQ and 3-MA enhanced the irradiation-induced apoptosis but inhibited viability of ORNJ fibroblasts. Silencing ATG7 with siRNA could obviously weaken irradiation-induced LC3-II expression, and promoted irradiation-induced apoptosis of ORNJ fibroblasts. After knockdown of ATG7, finally, p-AKT(Ser473) and p-mTOR(Ser2448) levels of ORNJ fibroblasts were significantly increased under irradiation.
CONCLUSION
Compared with normal fibroblasts, human gingival myofibroblasts are resistant to irradiation-induced apoptosis via autophagy activation. Silencing ATG7 may evidently inhibit activation of autophagy, and promote apoptosis of gingival myofibroblasts via Akt/mTOR pathway.
Topics: Humans; Apoptosis; Autophagy; Myofibroblasts; Proto-Oncogene Proteins c-akt; RNA, Small Interfering; TOR Serine-Threonine Kinases
PubMed: 37876026
DOI: 10.1111/jop.13490 -
Bulletin Du Cancer May 2024Osteoradionecrosis (ORN) is a late secondary iatrogenic complication of external radiotherapy for cancers of the upper aero-digestive tract. Despite the systematization... (Review)
Review
Osteoradionecrosis (ORN) is a late secondary iatrogenic complication of external radiotherapy for cancers of the upper aero-digestive tract. Despite the systematization of intensity-modulated radiotherapy and its potential for preserving salivary secretion and limiting the dose delivered to the supporting bone, ORN remains a feared and frequent complication. The objective of this literature review was to provide an overview of the management of ORN and to determine the key points that would make it possible to improve patient care. The diagnosis of ORN requires to eliminate tumor recurrence then is based on clinical arguments and imaging by CT or Cone Beam evolving in a chronic mode (more than 3-6 months). The harmonization of its classifications aims to offer comprehensive and multidisciplinary care as early as possible. Primary prevention is based on pre-therapeutic oral and dental preparation, then associated with fluoroprophylaxis if salivary recovery is insufficient and requires supervision of invasive dental care and prosthetic rehabilitation. Semi-automatic contouring tools make it possible to identify doses delivered to dental sectors and guide dental care with personalized dosimetric mapping. Conservative medical treatment is offered at an early stage where innovative medical treatments, highlighted by early studies, could be of interest in the future. In the event of advanced ORN, a non-conservative treatment is then proposed and frequently consists of interruptive mandibulectomy associated with reconstruction by bony free flap, the conditions of implantation remaining to be defined with the support of prospective clinical trials.
Topics: Humans; Osteoradionecrosis; Radiotherapy, Intensity-Modulated; Head and Neck Neoplasms; Primary Prevention; Dental Care; Neoplasm Recurrence, Local
PubMed: 38480057
DOI: 10.1016/j.bulcan.2024.01.008 -
Indian Journal of Otolaryngology and... Sep 2023
PubMed: 37636770
DOI: 10.1007/s12070-023-03639-y -
Anaerobe Aug 2023Members of the Actinomyces genus and Actinomyces-like organisms (ALOs; namely Actinotignum, Arcanobacterium, Schaalia and Varibaculum) are Gram-positive,... (Review)
Review
Members of the Actinomyces genus and Actinomyces-like organisms (ALOs; namely Actinotignum, Arcanobacterium, Schaalia and Varibaculum) are Gram-positive, non-spore-forming rods that are commensal members of the human oral cavity, gastrointestinal tract, female genital tract and skin microbiota. Cervicofacial actinomycosis or "lumpy jaw syndrome" - the chronic, suppurative granulomatous disease caused by Actinomyces spp. And ALOs - is characterized by an initially slow and unspecific disease-presentation, which often mimics other pathologies, followed by the formation of painful abscesses and severe tissue destruction. Actinomycosis has been described as a rare disease, however, reliable epidemiological data are lacking. In addition, there is increasing awareness regarding the role of Actinomyces spp. in the development of osteoradionecrosis and medication-related osteonecrosis of the jaw. The aim of this narrative review is to succinctly summarize the current advances regarding the microbiological, clinical, diagnostic and therapeutic aspects of cervicofacial actinomycosis, in addition to the roles of Actinomyces species and ALOs as members of the oral microbiota and in dental biofilm, in other dental infections (caries, root canal infection, periapical infection, periodontitis) and osteonecrosis of the jaw, in the context of recent taxonomic changes affecting the genus. Our paper aims to be a blueprint for dentists, other physicians, microbiologists and researchers regarding the multifaceted field of cervicofacial actinomycosis.
Topics: Female; Humans; Actinomyces; Actinomycosis; Actinomycosis, Cervicofacial; Mouth; Actinomycetaceae; Osteonecrosis
PubMed: 37482285
DOI: 10.1016/j.anaerobe.2023.102767 -
Oral Oncology Jan 2024Head and neck cancer ranks as the seventh most common cancer worldwide. Proton therapy is widely used in head and neck cancer. Osteoradionecrosis(ORN) is currently a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Head and neck cancer ranks as the seventh most common cancer worldwide. Proton therapy is widely used in head and neck cancer. Osteoradionecrosis(ORN) is currently a commonly investigated side effect of proton therapy. A meta-analysis is needed to investigate this topic.
MATERIAL/METHODS
Two authors searched three databases, including PubMed, Embase, and Cochrane Library; the search period was from inception to June 2023. The search keyword was set to be ((("osteoradionecrosis") OR ("osteonecrosis")) AND ("proton")).
RESULTS
We initially collected 410 articles, and after article selections, 22 articles remained in our systematic reviews. Due to the overlapping of patient populations, 17 studies were finally included in our meta-analysis. The pooled grade 3 or more ORN rate is 0.01(95 % CI = 0.01-0.03). Subgroup analysis showed that IMPT didn't reduce grade 3 or more ORN compared with 3DCPT (p = 0.15).
CONCLUSIONS
Our meta-analysis showed that severe ORN rarely occurred in proton therapy for head and neck cancer patients.
Topics: Humans; Osteoradionecrosis; Proton Therapy; Head and Neck Neoplasms; Retrospective Studies
PubMed: 38035508
DOI: 10.1016/j.oraloncology.2023.106649 -
Current Opinion in Supportive and... Mar 2024Osteoradionecrosis (ORN) is a devasting complication of radiation therapy (RT), especially in head and neck cancers (HNC), and is still poorly understood. The aim of... (Review)
Review
PURPOSE OF REVIEW
Osteoradionecrosis (ORN) is a devasting complication of radiation therapy (RT), especially in head and neck cancers (HNC), and is still poorly understood. The aim of this review is to report its incidence and consider the risk factors associated with ORN to highlight prevention strategies to decrease its incidence.
RECENT FINDINGS
The average incidence of ORN is between 2% and 23%, with incidence decreasing in more recent years with the introduction of modern RT technology and better oral health care. Smoking, diabetes mellitus, oropharyngeal and oral cavity cancers, pre- and post-RT dental extractions and a total radiation dose of over 60 Gy were all identified as risk factors for ORN. In prevention, strategies were mainly structured around minimising risk factors or targeting possible mechanisms of ORN's pathophysiology.
SUMMARY
At present, the controversy surrounding the risk factors and pathogenesis of ORN makes it difficult to establish a set of prevention guidelines for its incidence. In order to achieve this, more research examining its aetiology must be conducted as well as a universal staging system within which ORN may be classified.
Topics: Humans; Osteoradionecrosis; Head and Neck Neoplasms; Smoking; Risk Factors; Retrospective Studies
PubMed: 38170197
DOI: 10.1097/SPC.0000000000000690 -
Oral Oncology Oct 2023Oral toxicities such as osteoradionecrosis can be minimized by dental screening and prophylactic dental care prior to head and neck (HN) radiation therapy (RT). However,...
Oral toxicities such as osteoradionecrosis can be minimized by dental screening and prophylactic dental care prior to head and neck (HN) radiation therapy (RT). However, limited information is available about how dental insurance interacts with prophylactic dental care and osteoradionecrosis. To address this gap in knowledge, we conducted a cohort study of 2743 consecutive adult patients treated with curative radiation for HN malignancy who underwent pre-radiation dental assessment and where required, prophylactic dental treatment. Charts were reviewed to determine patient demographics, dental findings, dental treatment and development of osteoradionecrosis following radiation. Three insurance cohorts were identified: private-insured (50.4 %), public-insured (7.3 %), being patients with coverage through government-funded disability and welfare programs, and self-pay (42.4 %). More than half the public-insured patients underwent prophylactic pre-radiation dental extractions, followed by self-pay patients (44 %) and private-insured patients (26.6 %). After a median follow-up time of 4.23 years, 6.5 % of patients developed osteoradionecrosis. The actuarial rate of osteoradionecrosis in the public-insured patients was 14.7 % at 5-years post-RT, compared to 7.5 % in private-insured patients and 6.7 % in self-pay patients. On multivariable analysis, dental insurance status, DMFS160, age at diagnosis, sex, tumor site, nodal involvement, years smoked and gross income were all significant risk factors for tooth removal prior to HN radiation. However, only public-insured status, tumor site and years smoked were significant risk factors for development of osteoradionecrosis. Our findings demonstrate that lack of comprehensive dental coverage (patients who self-pay or who have limited coverage under public-insured programs) associates strongly with having teeth removed prior to HN RT. Nearly 1 in 6 patients covered under public-insurance developed osteoradionecrosis within 5 years of completing their treatment. Well-funded dental insurance programs for HN cancer patients might reduce the number of pre-RT extractions performed in these patients, improving quality of life post-RT.
Topics: Adult; Humans; Osteoradionecrosis; Cohort Studies; Quality of Life; Insurance, Dental; Head and Neck Neoplasms; Tooth Extraction; Retrospective Studies
PubMed: 37499325
DOI: 10.1016/j.oraloncology.2023.106527 -
Medicine and Pharmacy Reports Jan 2024The aim of this retrospective study was to identify the clinical, radiological, and histological characteristics of patients diagnosed with osteonecrosis of the jaw...
AIM
The aim of this retrospective study was to identify the clinical, radiological, and histological characteristics of patients diagnosed with osteonecrosis of the jaw (ONJ) and treated at the Oral and Maxillo-Facial Surgery Clinic of the Emergency Clinical County Hospital of Targu Mures between 2017 and 2022. The study aimed to analyze correlations between patient characteristics, particularly their history of bone modifying agent use or local radiotherapy during cancer treatment, in order to identify specific patient profiles that could aid in evaluating treatment response and guide individualized treatment strategies.
METHODS
Fifty-two patients diagnosed with ONJ were included in the study. The patients were divided into two groups based on their medical history: the bone modifying agent use group and the radiotherapy group. Clinical, radiological, and histological data were collected and analyzed. Statistical analysis, including p-values, was performed to compare patient characteristics between the two groups.
RESULTS
Patients in the radiotherapy group were significantly older than those in the bone modifying agent use group (66 years vs. 56.9 years, p=0.001). There was a higher proportion of males in the radiotherapy group compared to the bone modifying agent use group (90% vs. 22%, p<0.001). Jaw involvement was more prevalent in the radiotherapy group compared to the bone modifying agent use group (95% vs. 66%, p=0.018). Histological analysis showed a similar frequency of Actinomyces species in both groups (50% vs. 34%, p=0.264).
CONCLUSIONS
The findings of this study suggest the existence of two distinct patient profiles based on their treatment history (bone modifying agent use vs. radiotherapy) in ONJ. Patients in the radiotherapy group were older, predominantly male, and exhibited a higher prevalence of jaw involvement. Histological analysis revealed no significant differences in Actinomyces species frequency between the two groups. These distinct patient profiles may indicate different responses to treatment, emphasizing the need for individualized treatment strategies tailored to specific patient characteristics. Further research is warranted to validate these findings and develop personalized approaches for managing ONJ.
PubMed: 38344330
DOI: 10.15386/mpr-2610 -
Supportive Care in Cancer : Official... Oct 2023To investigate the survival rate in implants placement in irradiated and non-irradiated bone in patients undergoing head and neck cancer (HNC) treatment. We focused on... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To investigate the survival rate in implants placement in irradiated and non-irradiated bone in patients undergoing head and neck cancer (HNC) treatment. We focused on the consequences of the main complications, such as osteoradionecrosis and peri-implantitis.
METHODS
An electronic search conducted by PRISMA protocol was performed. Full texts were carefully assessed, and data were assimilated into a tabular form for discussion and consensus among the expert panel. The quality assessment and the risk of bias are verified by Joanna Briggs Institute checklist (JBI) and The Newcastle-Ottawa Scale (NOS), and Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) assessment tool.
RESULTS
A total of 452 records were identified in the based on our PICOs strategy and after screening, 19 articles were included in the descriptive analysis of the review. Totaling 473 implants placed in irradiated and non-irradiated bone, and 31.6% of the patients were over 60 years of age. 57.9%) performed implant placement in a period of 12 months or more after the ending of radiotherapy. Only 5 studies had a follow-up period longer than 5 years after implant placement, of which three were used for the meta-analysis. In the meta-analysis of 5-year survival rate, analysis of implants in irradiated bone was assessed; a random effect model was used and a weighted proportion (PP) of 93.13% (95% CI: 87.20-99.06; p < 0.001), and in the 5-year survival rate, analysis of implants in non-irradiated bone was analysed; a fixed effect model was used and a weighted proportion (PP) of 98.52% survival (95% CI: 97.56-99.48, p < 0.001).
CONCLUSIONS
Survival rates of implants placed in irradiated bone are clinically satisfactory after a follow-up of 5 years, with a fewer percentage than in implants placed in non-irradiated bone after metanalyses performed.
Topics: Humans; Middle Aged; Aged; Bone-Anchored Prosthesis; Head and Neck Neoplasms
PubMed: 37851170
DOI: 10.1007/s00520-023-08088-5