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1.
J Oral Maxillofac Surg ; 81(9): 1094-1101, 2023 09.
Article in English | MEDLINE | ID: mdl-37277099

ABSTRACT

BACKGROUND: In the fall of 2021, granisetron was approved for postoperative nausea and vomiting (PONV) management in Japan. However, the comparative efficacy of droperidol and granisetron in the field of orthognathic surgery has not been determined. PURPOSE: We compare the efficacy of droperidol and granisetron for PONV prophylaxis following orthognathic surgery. STUDY DESIGN, SETTING, SAMPLE: We performed a retrospective cohort study of patients who underwent orthognathic surgery at a single institution from September 2020 to December 2022. Patients who had undergone Le Fort I osteotomy with sagittal split ramus osteotomy or isolated sagittal split ramus osteotomy were included. Patients were divided into three groups; the isolated droperidol (D), isolated granisetron (G), and droperidol with granisetron (DG) groups. General anesthesia was performed using total intravenous anesthesia for all patients; however, droperidol and granisetron were administered at the anesthesiologist's discretion. PREDICTOR VARIABLE: PONV prophylactic therapy included isolated droperidol, isolated granisetron, and droperidol with granisetron administration. OUTCOME VARIABLES: Postoperative nausea (PON) and postoperative vomiting (POV) were determined through medical examination within 48 hours following surgery. Secondary outcomes included complications due to droperidol and/or granisetron administration. COVARIATES: Age, sex, body mass index, Apfel's score, duration of surgery, duration of anesthesia, intraoperative blood loss, and type of surgery. ANALYSES: Statistical analysis was conducted using Fisher exact test, Mann-Whitney U test with Bonferroni correction for univariate comparison, and modified Poisson regression for comparison of PON and POV prophylactic efficacy for multivariate analyses. P values <.05 were considered statistically significant. RESULTS: Our study included 218 participants. There were no significant differences in covariates between groups D (n = 111), G (n = 52), and DG (n = 55). No significant difference in PON incidence was observed between groups. However, POV incidence was significantly lower in group DG than group D (relative risk, 0.21; 95% confidence interval, 0.05 to 0.86; P = .03). No significant difference in complication incidence was observed between groups. CONCLUSIONS AND RELEVANCE: Granisetron was as effective as droperidol for PONV management, while droperidol combined with granisetron was more effective than isolated droperidol for POV management. As compared to the use of each drug separately, their combination was considered safe, with no increase in complication rates.


Subject(s)
Antiemetics , Orthognathic Surgery , Humans , Droperidol/therapeutic use , Granisetron/therapeutic use , Postoperative Nausea and Vomiting/prevention & control , Retrospective Studies , Antiemetics/therapeutic use , Vomiting/drug therapy , Vomiting/prevention & control , Double-Blind Method
2.
J Dent Sci ; 17(2): 870-875, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35756779

ABSTRACT

Background/purpose: The epidemiology of infective endocarditis (IE) is under constant change due to the aging society and increases in antimicrobial-resistant pathogens. However, IE remains severe. This study aimed to review the current clinical characteristics of IE and the antimicrobial susceptibility of oral bacteria (OB) isolated from blood cultures to implement appropriate antimicrobial prophylaxis. Materials and methods: We retrospectively investigated the clinical features of 180 patients with IE in whom OB and pathogens except OB (eOB) were identified as causative microorganisms via blood cultures. The susceptibility of the OB group to eight antibiotics was examined by broth microdilution. Results: Among causative microorganisms, the isolation rate of staphylococci was slightly higher than that of OB; however, the difference was not significant (36.7% vs. 33.8%, p = 0.3203). The number of patients with underlying cardiac disease was significantly higher in the OB group than in the eOB group (53.7% vs. 34.1%, p = 0.0113). Only one ampicillin-resistant OB was detected (2.0%). OBs were significantly less susceptible to clarithromycin and azithromycin than to ampicillin (98.0% vs. 66.7% and 98.0% vs. 60.0%, p = 0.0003 and p = 0.0003, respectively). Moreover, OBs were significantly less susceptible to clarithromycin and azithromycin than to clindamycin (66.7% vs. 88.2% and 60.0% vs. 88.2%, p = 0.0301 and p = 0.0217, respectively). Conclusion: OBs were susceptible to ampicillin. However, the susceptibility of OBs to clarithromycin and azithromycin was significantly lower than that to ampicillin and clindamycin. These results are important and should help decisions regarding guide antimicrobial prophylaxis.

3.
J Med Case Rep ; 16(1): 6, 2022 Jan 03.
Article in English | MEDLINE | ID: mdl-34980242

ABSTRACT

BACKGROUND: The postoperative complications of mandibular fracture include malocclusion, infection, nonunion, osteomyelitis, and sensorial mental nerve dysfunction. However, there are no reports regarding postoperative dysphagia as a complication of mandibular fracture. Herein, we report a rare case of postoperative dysphagia caused by delayed mandibular fracture treatment in a patient with severe intellectual disability. CASE PRESENTATION: A 46-year-old Japanese male patient with severe intellectual disability fell down and struck his chin. The patient was referred to our department 10 days after the accident. Upon examination, he could not close his mouth because of severe left mandibular body fracture. Open reduction and internal fixation was performed under general anesthesia 16 days after sustaining the injury, and normal occlusion was eventually achieved. However, the patient could not swallow well a day after surgery. He was then diagnosed with postoperative dysphagia caused by disuse atrophy of muscles for swallowing based on videoendoscopic examination findings. Adequate dysphagia rehabilitation could not be facilitated because of the patient's mental status. Postoperative dysphagia did not improve 21 days after surgery. Therefore, percutaneous endoscopic gastrostomy was required. CONCLUSIONS: The treatment course of the patient had two important implications. First, postoperative dysphagia caused by disuse atrophy may occur if treatment is delayed in severe mandibular body fracture. Second, in particular, if a patient with severe intellectual disability develops postoperative dysphagia caused by disuse atrophy, adequate dysphagia rehabilitation cannot be facilitated, and percutaneous endoscopic gastrostomy may be required. Therefore, early open reduction and internal fixation is required for mandibular fracture in a patient with severe intellectual disability.


Subject(s)
Deglutition Disorders , Intellectual Disability , Mandibular Fractures , Deglutition Disorders/etiology , Fracture Fixation, Internal , Humans , Intellectual Disability/complications , Male , Mandible , Mandibular Fractures/surgery , Middle Aged
4.
Support Care Cancer ; 30(3): 2341-2348, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34738163

ABSTRACT

PURPOSE: This study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis. METHODS: The medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups. RESULTS: Among the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65-5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38-7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score-matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17-5.01; p = 0.016). CONCLUSION: The results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Bone Neoplasms , Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bone Density Conservation Agents/adverse effects , Bone Neoplasms/drug therapy , Denosumab/adverse effects , Diphosphonates/adverse effects , Humans , Propensity Score , Retrospective Studies , Zoledronic Acid/adverse effects
5.
Cancer Chemother Pharmacol ; 87(6): 871-877, 2021 06.
Article in English | MEDLINE | ID: mdl-33791853

ABSTRACT

PURPOSE: Switch from zoledronic acid (ZA) to denosumab may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) owing to the additive effect of denosumab on the jawbone and residual ZA activities. We evaluated the risk of developing MRONJ in patients who received ZA, denosumab, or ZA-to-denosumab for the treatment of bone metastases. METHODS: The medical charts of patients with cancer who received denosumab or ZA for bone metastases were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. Primary endpoint was the evaluation of the risk of developing MRONJ in the ZA-to-denosumab group. Secondary endpoints were probability of MRONJ and the relationship between risk factors and the time to the development of MRONJ. RESULTS: Among the 795 patients included in this study, 65 (8.2%) developed MRONJ. The incidence of MRONJ was significantly higher in the ZA-to-denosumab group than in the ZA group [7/43 (16.3%) vs. 19/350 (5.4%), p = 0.007]. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment [hazard ratio (HR), 2.41; 95% confidence interval (CI), 1.37-4.39; p = 0.002], ZA-to-denosumab treatment (HR, 4.36; 95% CI, 1.63-10.54, p = 0.005), tooth extraction after starting ZA or denosumab (HR, 4.86; 95% CI, 2.75-8.36; p < 0.001), and concomitant use of antiangiogenic agents (HR, 1.78; 95% CI, 1.06-2.96; p = 0.030) were significant risk factors for MRONJ. CONCLUSION: Our results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.


Subject(s)
Bone Density Conservation Agents/adverse effects , Bone Density Conservation Agents/therapeutic use , Bone Neoplasms/drug therapy , Denosumab/adverse effects , Denosumab/therapeutic use , Jaw/drug effects , Osteonecrosis/chemically induced , Zoledronic Acid/therapeutic use , Aged , Angiogenesis Inhibitors/therapeutic use , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , Tooth Extraction/methods
6.
Support Care Cancer ; 29(8): 4763-4772, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33527228

ABSTRACT

PURPOSE: This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. METHODS: The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. RESULTS: Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). CONCLUSION: The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/epidemiology , Bone Density Conservation Agents/therapeutic use , Denosumab/therapeutic use , Zoledronic Acid/therapeutic use , Aged , Bone Density Conservation Agents/pharmacology , Denosumab/pharmacology , Diphosphonates/therapeutic use , Female , Humans , Male , Neoplasm Metastasis , Retrospective Studies , Treatment Outcome , Zoledronic Acid/pharmacology
7.
J Med Case Rep ; 15(1): 66, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33583426

ABSTRACT

BACKGROUND: Acquired hemophilia A is a rare coagulopathy caused by inhibitors of blood coagulation factor VIII. Patients with acquired hemophilia A have a higher mortality risk (5-10%) than those with congenital hemophilia. Moreover, there is no established evidence of management recommended for patients with acquired hemophilia A. Previous studies have reported the presence of hematomas in the oral cavities of patients with acquired hemophilia A, which were treated conservatively. Here, we describe the case of a patient with acquired hemophilia A, where emergency surgical hemostasis was required for large intraoral hematomas. CASE PRESENTATION: A 65-year-old Japanese man was referred to our hospital with a chief complaint of bleeding from large intraoral hematomas. On examination, he could not close his mouth because of the hematomas, which were bleeding spontaneously. Computed tomography angiography revealed no evidence of arteriovenous malformation, and blood test results showed that the activated partial thromboplastin time was elevated beyond the normal limit. To avoid a life-threatening hemorrhage from hematomas, emergency surgical hemostasis was performed with nasotracheal intubation using fiberoptic bronchoscopy. Hemostasis was successfully performed, as the hematomas were carefully removed. Moreover, the clinical course was successfully completed using intravenously administered activated prothrombin complex concentrate for hemostasis after operation. CONCLUSIONS: Acquired hemophilia A can cause a life-threatening hemorrhage without predictive factors. Intraoral hematoma may cause airway obstruction. There is no consensus regarding the management of hemorrhage in patients with acquired hemophilia A. As shown here, exophytic hematomas in the oral cavity can be safely removed and nasotracheal intubation with fiberoptic bronchoscopy may be useful in patients with coagulopathy disease.


Subject(s)
Hemophilia A , Aged , Factor VIII , Hematoma/diagnostic imaging , Hematoma/etiology , Hematoma/therapy , Hemophilia A/complications , Hemophilia A/drug therapy , Hemostasis, Surgical , Humans , Male , Mouth
8.
Cureus ; 13(12): e20446, 2021 Dec.
Article in English | MEDLINE | ID: mdl-35047283

ABSTRACT

Infective endocarditis is an extremely serious disease that can present with a variety of clinical manifestations, including infection of valves and endocardium, in patients with cardiac disease, and is associated with risk factors such as invasive dental procedures, caries, and periodontal disease. On the other hand, it has been shown that perioperative oral function management before various surgeries, such as those for malignant tumors, cardiovascular disease, and transplantation, may prevent or reduce postoperative complications. Close coordination between the dentist and cardiac surgeon is especially necessary before heart valve surgery because of the risk of severe complications. The number of perioperative oral management procedures being performed in community dental clinics is increasing. In the absence of clear guidelines, the physician-in-charge usually determines how to best perform oral management while considering the patient's needs. We report a case of infective endocarditis occurring after perioperative oral management in a young patient with good oral hygiene. This case shows that standardization of the techniques and widespread dissemination of the guidelines are required. Patients should be counseled regarding the importance of maintaining oral hygiene from a young age. This case report should act as a cautionary tale not only for hospital clinicians but also for community medical and dental practitioners, as the number of such patients is expected to increase in the future.

9.
Case Rep Dent ; 2020: 8871148, 2020.
Article in English | MEDLINE | ID: mdl-33457021

ABSTRACT

Computer-assisted navigation plays an important role in modern craniomaxillofacial surgery. Although headpins and skull posts are widely used for the fixation of the reference frame, they require the use of invasive procedures. Headbands are easily displaced intraoperatively, thus reducing the accuracy of the surgical outcome. This study reported the utility of a novel splint integrated with a reference frame and registration markers for maxillary navigation surgery. A maxillary splint with a 10 cm resin handle was fabricated before surgery, to fix the reference frame to the splint. The splint was set after the incorporation of fiducial gutta-percha markers into both the splint and resin handle for marker-based pair-point registration. A computed tomography (CT) scan was acquired for preoperative CT-based planning. A marker-based pair-point registration procedure can be completed easily and noninvasively using this custom-made integrated splint, and maxillary navigation surgery can be performed with high accuracy. This method also provides maximum convenience for the surgeon, as the splint does not require reregistration, and can be removed temporarily when required. The splint-to-CT data registration strategy has potential applicability not only for maxillary surgery but also for otolaryngologic surgery, neurosurgery, and surgical repair after craniofacial trauma.

10.
Case Rep Dent ; 2019: 5421706, 2019.
Article in English | MEDLINE | ID: mdl-31467733

ABSTRACT

The common postoperative complications of the extraction of third molars are frequently reported; however, reports about osteomyelitis of the mandible caused by late fracture following third molar extraction are rare. Here, we report a case of osteomyelitis of the mandible caused by late fracture following third molar extraction. A 38-year-old Japanese man was referred to the surgery department with chief complaints of dull pain and swelling in the right masseteric region and paresthesia of his lower lip and mental region in March 2018. A family dentist removed his lower third molar in the right side in January 2018. When the patient was chewing an innards stew 23 days after the procedure, he heard a cracking sound from the right mandible. Thus, we diagnosed the patient as having osteomyelitis of the mandible caused by late fracture following third molar extraction and performed sequestrectomy and curettage under general anesthesia in April 2018. In conclusion, it is necessary to recognize the possibility that late fracture following third molar extraction can cause osteomyelitis. Furthermore, once osteomyelitis of the mandible caused by late fracture occurred, early and appropriate treatment is necessary because the osteomyelitis may progress rapidly and in some cases may result in pathological fracture.

11.
J Oral Implantol ; 44(5): 359-364, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29870295

ABSTRACT

Dental implant treatment is a highly predictable therapy, but when potentially lethal symptoms or complications occur, dentists must remove the implant fixture. Recently, reports on antiresorptive agent-related osteonecrosis of the jaw have increased in the field of dental implants, although the relationship between dental implant treatment and antiresorptive agents remains unclear. Here, we report a case of antiresorptive agent-related osteonecrosis of the jaw that developed after dental implant removal. A 67-year-old Japanese woman with a medical history of osteoporosis and 7 years of oral bisphosphonate treatment was referred to our hospital with a chief complaint of painful right mandibular bone exposure. A family dentist removed the dental implants from the right mandible using a trephine drill without flap elevation in August 2016. However, the healing was impaired; she was referred to our hospital 3 months after the procedure. We performed a sequestrectomy of the mandible under general anesthesia. In conclusion, this patient's course has two important implications: First, the removal of dental implants from patients who are prescribed oral bisphosphonates for long durations can cause antiresorptive agent-related osteonecrosis of the jaw. Second, meticulous procedures are required to prevent and treat the development of antiresorptive agent-related osteonecrosis of the jaw after dental implant removal.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Dental Implants , Osteonecrosis , Aged , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bone Density Conservation Agents/adverse effects , Diphosphonates/adverse effects , Female , Humans , Tooth Extraction
12.
J Oral Maxillofac Surg ; 76(10): 2122-2130, 2018 10.
Article in English | MEDLINE | ID: mdl-29782813

ABSTRACT

Actinomycosis is a rare, chronic, slowly progressive granulomatous disease caused by filamentous gram-positive anaerobic bacteria from the Actinomycetaceae family (genus Actinomyces). It has become a rare condition because of the widespread use of antibiotics. When clinical symptoms are not typical, diagnosis of this condition becomes difficult. This report describes a case involving an 82-year-old woman who was diagnosed with actinomycotic osteomyelitis of the mandible using matrix assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS). The patient was referred to the authors' department with chief complaints of swelling, multiple fistulae in the left preauricular region, and trismus. The authors performed fine-needle aspiration microbiology (FNAM) and identified Actinomyces oris using MALDI-TOF MS. A diagnosis of actinomycotic osteomyelitis of the mandible was made and the patient was treated with minocycline and extraction of the culprit tooth. The findings from this case have 2 important implications. First, for patients with clinically suspected actinomycosis, bacteriologic examinations should include not only surface swab tests but also FNAM; moreover, communication with the laboratory medical technologist is important to improve detection of the causative organisms. Second, MALDI-TOF MS could be an effective tool for improving the diagnosis and treatment outcomes of actinomycosis.


Subject(s)
Actinomycosis/diagnostic imaging , Mandibular Diseases/diagnostic imaging , Mandibular Diseases/drug therapy , Mandibular Diseases/microbiology , Osteomyelitis/diagnostic imaging , Osteomyelitis/microbiology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Actinomycosis/drug therapy , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Female , Humans , Magnetic Resonance Imaging/methods , Minocycline/therapeutic use , Osteomyelitis/drug therapy , Tomography, X-Ray Computed/methods , Treatment Outcome
13.
J Oral Implantol ; 43(5): 360-364, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28841394

ABSTRACT

Maxillary sinus floor augmentation is considered to play a critical role in dental implant treatment. Although many complications, such as maxillary sinusitis and infection, are well known, few reports are available on the risk of surgical ciliated cyst following the procedure. Here, we report a case of surgical ciliated cyst following maxillary sinus floor augmentation. A 55-year-old Japanese woman was referred to our hospital because of alveolar bone atrophy in the bilateral maxilla. We performed bilateral maxillary sinus floor augmentation by the lateral window technique without covering the window. The Schneiderian membrane did not perforate during the operation. She returned to our hospital after 9 years due to swelling of the left buccal region. Computerized tomography revealed a well-defined radiolucent area with radiodense border intraosseously localized in the left maxilla. We performed enucleation of the cyst with the patient under general anesthesia. Histological examination of the specimen showed a surgical ciliated cyst. In conclusion, the course of this patient has 2 important implications. First, the sinus membrane entrapped in the grafted bone without visible perforation and or tearing can develop into a surgical ciliated cyst. Second, there is a possibility that covering the lateral window tightly might prevent the development of a surgical ciliated cyst.


Subject(s)
Cysts , Dental Implants , Sinus Floor Augmentation , Cysts/etiology , Female , Humans , Maxilla , Maxillary Sinus , Middle Aged , Sinus Floor Augmentation/adverse effects
14.
Angew Chem Int Ed Engl ; 53(6): 1659-63, 2014 Feb 03.
Article in English | MEDLINE | ID: mdl-24453181

ABSTRACT

Helical carbon and graphite films from helical poly(3,4-ethylenedioxythiophene) (H-PEDOT) films synthesized through electrochemical polymerization in a chiral nematic liquid-crystal (N*-LC) field are prepared. The microscope investigations showed that the H-PEDOT film synthesized in the N*-LC has large domains of one-handed spiral morphology consisting of fibril bundles. The H-PEDOT films exhibited distinct Cotton effects in circular dichroism spectra. The highly twisted N*-LC with a helical pitch of smaller than 1 µm produced the H-PEDOT film with a highly ordered morphology. The spiral morphologies with left- and right-handed screws were observed for the carbon films prepared from the H-PEDOT films at 800 °C and were well correlated with the textures and helical pitches of the N*-LCs. The spiral morphologies of the precursors were also retained even in the graphite films prepared from the helical carbon films at 2600 °C.

15.
Mol Cancer Res ; 12(1): 58-68, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24307696

ABSTRACT

UNLABELLED: NF-E2-related factor 2 (NRF2) is a master transcriptional regulator that integrates cellular stress responses and is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1) at the posttranslational level. In human cancers, aberrantly stabilized NRF2, either by mutation of NRF2 or KEAP1, plays a vital role in chemoresistance and tumor cell growth through the transcriptional activation of target genes, suggesting that targeted inhibition of NRF2 is a potential therapy for NRF2-stabilized tumors. MicroRNAs (miRNA) are endogenous small noncoding RNAs that can negatively regulate gene expression by interfering with the translation or stability of target transcripts. Moreover, tumor-suppressor miRNAs have been suggested to be useful for cancer treatment. Here, a reporter-coupled miRNA library screen identified four miRNAs (miR-507, -634, -450a, and -129-5p) that negatively regulate the NRF2-mediated oncogenic pathway by directly targeting NRF2. Importantly, downregulation of these miRNAs, in addition to the somatic mutation of NRF2 or KEAP1, is associated with stabilized NRF2 and poor prognosis in esophageal squamous cell carcinoma (ESCC). Furthermore, administration of a miR-507 alone or in combination with cisplatin inhibited tumor growth in vivo. Thus, these findings reveal that miRNA-based therapy is effective against NRF2-stabilized ESCC tumors. IMPLICATIONS: This study determines the potential of miRNA-based molecular diagnostics and therapeutics in NRF2-stablized tumors.


Subject(s)
Carcinoma, Squamous Cell/drug therapy , Esophageal Neoplasms/drug therapy , Intracellular Signaling Peptides and Proteins/genetics , MicroRNAs/pharmacology , NF-E2-Related Factor 2/genetics , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/mortality , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival , Cisplatin/pharmacology , Down-Regulation , Esophageal Neoplasms/genetics , Esophageal Neoplasms/mortality , Esophageal Squamous Cell Carcinoma , Female , Gene Expression Regulation , HeLa Cells , Humans , Kelch-Like ECH-Associated Protein 1 , Male , Mice , Mice, Inbred BALB C , MicroRNAs/biosynthesis , MicroRNAs/genetics , Middle Aged , Molecular Diagnostic Techniques , Mutation , Prognosis , RNA Interference , RNA, Small Interfering
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