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BACKGROUND: Pancreaticoduodenectomy has been associated with a high mortality rate and significant postoperative morbidity. Recently, perioperative oral care management has been reported to be effective in preventing postoperative pneumonia and surgical site infection. In this study, we examined the effect of perioperative oral care management in reducing complications after pancreaticoduodenectomy, including surgical site infection. METHODS: This retrospective multicenter study included 503 patients who underwent pancreaticoduodenectomy at 8 facilities between January 2014 and December 2016. Among these, 144 received perioperative oral management by dentists and dental hygienists (oral management group), whereas the remaining 359 did not (control group). The oral care management program included oral health instructions, removal of dental calculus, professional mechanical tooth cleaning, removal of tongue coating, denture cleaning, instructions for gargling, and tooth extraction. The participants were matched using propensity scores to reduce background bias. Various factors were examined for correlation with the development of complications. RESULTS: The incidence of organ/space surgical site infection was significantly lower in the oral management group than in the control group (8.0% vs 19.6%, P = .005). Multivariable logistic regression analysis revealed that hypertension and lack of perioperative oral management were independent risk factors for organ/space surgical site infection. Lack of perioperative oral management had an odds ratio of 2.847 (95% confidence interval 1.335-6.071, P = .007). CONCLUSION: Perioperative oral care management reduces the occurrence of surgical site infections after pancreaticoduodenectomy and should be recommended as a strategy to prevent infections in addition to antibiotic use.
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Neoplasias , Infección de la Herida Quirúrgica , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & control , Puntaje de Propensión , Pancreaticoduodenectomía/efectos adversos , Estudios Retrospectivos , Neoplasias/complicaciones , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
Lower third molar extraction is the most common surgical treatment among routine dental and oral surgical procedures. while the surgical procedures for lower third molar extraction are well established, the difficulty of tooth extraction and the frequency of postoperative complications differ depending on the patient's background. To establish a management protocol for the lower third molars, the prevalence of and risk factors for postoperative complications after lower third molar extraction were investigated in a large number of Japanese patients in a multicenter prospective study. During 6 consecutive months in 2020, 1826 lower third molar extractions were performed at the 20 participating institutions. The medical records of the patients were reviewed, and relevant data were extracted. The prevalence of and risk factors for postoperative complications were analyzed. The prevalence of postoperative complications after lower third molar extraction was 10.0%. Multivariate analysis indicated that age (≤32 vs >32, odds ratio [OR]: 1.428, 95% confidence interval [95% CI]: 1.040-1.962, P < .05), the radiographic anatomical relationship between the tooth roots and mandibular canal (overlapping of the roots and canal vs no close anatomical relationship between the roots and the superior border of the canal, OR: 2.078, 95% CI: 1.333-3.238, P < .01; overlapping of the roots and canal vs roots impinging on the superior border of the canal, OR: 1.599, 95% CI: 1.050-2.435, P < .05), and impaction depth according to the Pell and Gregory classification (position C vs position A, OR: 3.7622, 95% CI: 2.079-6.310, P < .001; position C vs position B, OR: 2.574, 95% CI: 1.574-4.210, P < .001) are significant independent risk factors for postoperative complications after lower third molar extraction. These results suggested that higher age and a deeply impacted tooth might be significant independent risk factors for postoperative complications after lower third molar extraction.
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Tercer Molar , Diente Impactado , Humanos , Japón/epidemiología , Mandíbula/cirugía , Tercer Molar/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Extracción Dental/efectos adversos , Diente Impactado/cirugíaRESUMEN
BACKGROUND: Surgical site infection is a common postoperative complication of colorectal cancer surgery, and surgical site infection increases medical costs, prolongs hospitalization, and worsens long-term prognosis. Perioperative oral care has been reported to be effective in preventing postoperative pneumonia, although there are only a few reports on its effectiveness in preventing surgical site infection. This study aimed to determine the role of perioperative oral care in surgical site infection prevention after colorectal cancer surgery. METHODS: In this study, 1,926 patients with colorectal cancer from 8 institutions were enrolled; 808 patients (oral care group) received perioperative oral care at the hospital's dental clinic, and 1,118 (control group) did not receive perioperative oral care. The data were matched by propensity score to reduce bias. Ultimately, a total of 1,480 patients were included in the analysis. RESULTS: The incidence of surgical site infection was significantly lower in the oral care group than in the control group (8.4% vs 15.7%, P < .001). Multivariate logistic regression analysis revealed 4 independent risk factors for surgical site infection: low albumin level, rectal cancer, blood loss, and lack of perioperative oral care. Lack of perioperative oral care had an odds ratio of 2.100 (95% confidence interval 1.510-2.930, P < .001). CONCLUSION: These results suggest that perioperative oral care can reduce the incidence of surgical site infection after colorectal cancer resection. Perioperative oral care may have an important role in the future perioperative management of colorectal cancer as a safe and effective method of surgical site infection prevention, although further validation in prospective studies is needed.
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Neoplasias Colorrectales , Infección de la Herida Quirúrgica , Neoplasias Colorrectales/cirugía , Humanos , Atención Perioperativa/métodos , Puntaje de Propensión , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Infección de la Herida Quirúrgica/prevención & controlRESUMEN
INTRODUCTION: This is a randomised, multi-centre, open-label, phase II study to evaluate the efficacy of betamethasone valerate ointment on radiation-induced oral mucositis in patients with head and neck cancer undergoing concomitant radiotherapy with cisplatin or cetuximab. METHODS AND ANALYSIS: The trial will take place at seven hospitals in Japan. Patients will be randomised (1:1) into betamethasone and control groups after the occurrence of grade 1 oral mucositis. In the betamethasone group, patients will use betamethasone valerate ointment five times a day, in addition to usual oral hygiene guidance. The primary endpoint is the incidence and onset time of grade 3 oral mucositis. The secondary endpoints are the incidence and onset time of grade 2 oral mucositis, incidence and onset time of oral candidiasis, completion of radiation therapy and adverse events. Target accrual is 102 patients with a two-sided type I error rate of 5% and 80% power to detect an 80% risk reduction in the incidence of grade 3 oral mucositis. ETHICS AND DISSEMINATION: This study was approved by the Clinical Research Review Board of Nagasaki University (No. CRB20-009). All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publication. The datasets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs071200013.
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Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Traumatismos por Radiación , Estomatitis , Valerato de Betametasona/uso terapéutico , Ensayos Clínicos Fase II como Asunto , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Estudios Multicéntricos como Asunto , Pomadas/uso terapéutico , Neoplasias Orofaríngeas/radioterapia , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Estomatitis/tratamiento farmacológico , Estomatitis/etiología , Estomatitis/prevención & controlRESUMEN
The prognosis of oral squamous cell carcinoma (OSCC) largely depends on the control of lymph node metastases. We evaluate the therapeutic efficacy of G47Δ, a third-generation oncolytic herpes simplex virus type 1 (HSV-1), in mouse tongue cancer models. Intratumoral injection with G47Δ prolonged the survival in all orthotopic models investigated. In both athymic and immunocompetent models, G47Δ injected into the tongue cancer swiftly traffics to the draining cervical lymph nodes and suppresses lymph node metastases. In the immunocompetent KLN205-MUC1 model, in which the metastatic cascade that tongue cancer patients commonly experience is reproduced, intratumoral G47Δ injection even immediately prior to a tumor resection prolonged survival. Cervical lymph nodes 18 h after G47Δ treatment showed the presence of G47Δ infection and an increase in CD69-positive cells, indicating an immediate activation of T cells. Furthermore, G47Δ injected directly into enlarged metastatic lymph nodes significantly prolonged the survival at an advanced stage. Whereas intratumorally injected oncolytic HSV-1 does not readily circulate in the blood stream, G47Δ is shown to traffic in the lymphatics swiftly. The use of G47Δ can lead to entirely new treatment strategies for tongue cancer and other OSCC at all clinical stages.
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Rac proteins, members of the Rho family of small GTP-binding proteins, have been implicated in transducing a number of signals for various biological mechanisms, including cell cytoskeleton organization, transcription, proliferation, migration, and cancer cell motility. Among human cancers, Rac proteins are highly activated by either overexpression of the genes, up-regulation of the protein, or by mutations that allow the protein to elude normal regulatory signaling pathways. Rac proteins are involved in controlling cell survival and apoptosis. The effects of Rac inhibition by the Rac-specific small molecule inhibitor NSC23766 or by transfection of dominant negative Rac (Rac-DN) were examined on three human-derived oral squamous cell carcinoma cell lines that exhibit different malignancy grades, OSC-20 (grade 3), OSC-19 (grade 4C), and HOC313 (grade 4D). Upon suppression of Rac, OSC-19 and HOC313 cells showed significant decreases in Rac activity and resulted in condensation of the nuclei and up-regulation of c-Jun N-terminal kinase (JNK), leading to caspase-dependent apoptosis. In contrast, OSC-20 cells showed only a slight decrease in Rac activity, which resulted in slight activation of JNK and no change in the nuclei. Fibroblasts treated with NSC23766 also showed only a slight decrease in Rac activity with no change in the nuclei or JNK activity. Our results indicated that apoptosis elicited by the inhibition of Rac depended on the extent of decreased Rac activity and the malignant state of the squamous cell carcinoma. In addition, activation of JNK strongly correlated with apoptosis. Rac inhibition may represent a novel therapeutic approach for cancer treatment.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Proteínas de Unión al GTP rac/metabolismo , Aminoquinolinas/farmacología , Apoptosis/efectos de los fármacos , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Proteína Quinasa 8 Activada por Mitógenos/metabolismo , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Pirimidinas/farmacología , Transducción de Señal/efectos de los fármacos , Transfección/métodosRESUMEN
Patients develop a number of oral complications during cancer treatments. Oral bacteria are associated with the onset of dental focal infections and the progression of oral mucositis. Dental focal infections are frequently associated with the systemic onset of bacteremia, sepsis, and pneumonia. The degeneration of oral function with these complications may become an obstacle to cancer treatments. Although comprehensive oral management, including oral care, the removal of dental focal infections, and improvements in oral function with dentures, is conducted for cancer patients in Japan, few studies have assessed its efficacy.The aim of the present study was to investigate the incidence of dental/oral complications in cancer patients with perioperative oral managements (POMs) based on a large number of case series with a multicenter retrospective analysis.The medical records of cancer patients with POMs were retrospectively reviewed and the incidence of oral complications and efficacy of oral management were investigated.A total of 2744 cancer patients with POMs (1684 males and 1080 females, mean age 65.9â±â13.0âyears) were included and investigated in the present study. Among these patients, 2097 (76.4%) started POM before the initiation of cancer treatments, with 2130 (77.6%) receiving oral care only and 391 (14.2%) being subjected to invasive treatments, such as tooth extraction. The incidence of dental focal infections during the period of cancer treatments was 8.2%. The most frequent infection was acute periodontitis, including alveolar abscesses (112 patients, 4.1%). The incidence of grade 2 and 3 oral mucositis was 2.8%. Prolonged fever was observed in 113 patients (4.1%), with 7 having dental focal infections (6.2%). These incidence rates were lower than those reported previously.Based on analyses of a large number of patients, the present results support the efficacy of oral management in cancer patients. However, further studies are needed to establish adequate oral management guidelines for cancer patients.
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Antineoplásicos/efectos adversos , Neoplasias/terapia , Estomatitis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Japón/epidemiología , Masculino , Persona de Mediana Edad , Atención Perioperativa , Estudios Retrospectivos , Factores de Riesgo , Estomatitis/etiología , Estomatitis/prevención & control , Adulto JovenRESUMEN
Postoperative hemorrhage after tooth extraction is a critical and clinically important issue for clinicians and patients receiving anticoagulants. The purpose of the present study was to investigate the prevalence of and risk factors for postoperative hemorrhage after lower third molar extraction in Japanese patients receiving warfarin therapy. A total of 142 patients who underwent lower third molar extraction between January 2010 and December 2016 were included, and their medical records were retrospectively reviewed. The prevalence of and risk factors for postoperative hemorrhage were investigated. The prevalence of postoperative hemorrhage after lower third molar extraction was significantly higher in patients receiving warfarin than in healthy subjects (21.8% vs 0.7%, P < 0.001). The cutoff value for PT-INR was 2.11 based on a receiver-operating characteristic analysis. A multivariate analysis indicated that an elevated PT-INR value [hazard ratio (HR) 3.798, 95% confidence interval (CI) 1.400-10.467, P < 0.01], preoperative antibiotic administration (HR 4.434, 95% CI 1.591-14.775, P < 0.01), difficulties with intraoperative hemostasis (HR 16.298, 95% CI 2.986-110.677, P < 0.01), and higher serum creatinine levels (HR 7.465, 95% CI 1.616-39.576, P < 0.05) are significant predictors of postoperative hemorrhage after lower third molar extraction. Multivariate correlations were observed between risk factors including an elevated PT-INR value, preoperative antibiotic administration, and higher serum creatinine levels, and postoperative hemorrhage after lower third molar extraction in patients receiving warfarin therapy. Clinicians need to consider these risk factors for postoperative hemorrhage after the lower third molar extraction and monitor PT-INR in patients receiving warfarin therapy.
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Tercer Molar , Warfarina , Anticoagulantes , Humanos , Relación Normalizada Internacional , Japón , Hemorragia Posoperatoria , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Extracción DentalRESUMEN
Treatment strategies of medication-related osteonecrosis of the jaw (MRONJ) are controversial. Recently, surgical treatment has been reported as superior to nonsurgical treatment, but the contribution discontinued antiresorptive agent use during MRONJ treatment remains unclear. This study aimed to evaluate the efficacy of drug holidays and treatment strategies in MRONJ cases. Four-hundred and twenty-seven patients with MRONJ treated at nine hospitals from 2009 to 2017 were included in this multicenter retrospective study. Multivariate Cox regression analysis showed that the primary disease (osteoporosis or malignant tumor), diabetes, serum albumin, and treatment method (surgical or nonsurgical) were significantly correlated with the cure rate. The cumulative 1-year cure rates in the surgical and nonsurgical treatment groups were 64.7% and 18.2%, respectively. However, discontinuing antiresorptive agents did not influence the treatment outcome in the cohort overall, or in 230 patients after performing propensity score matching among the discontinuation and continuation groups. When stratifying by treatment method, antiresorptive agent discontinuation significantly increased the cure rate in patients with osteoporosis who underwent nonsurgical treatment. In patients with malignant tumors undergoing nonsurgical therapy, discontinuing the antiresorptive agent was associated with a better treatment outcome, but not with statistical significance. In contrast, drug holidays showed no effect on improving outcomes in patients with both osteoporosis and malignant tumors who underwent surgical therapy. Thus, regardless of the primary disease, discontinuing antiresorptive agents during treatment for MRONJ may not be necessary and may be helpful in some cases. Future prospective trials should examine this question further.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos/tratamiento farmacológico , Conservadores de la Densidad Ósea/uso terapéutico , Anciano , Estudios de Cohortes , Femenino , Humanos , Estudios Longitudinales , Masculino , Análisis Multivariante , Puntaje de Propensión , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Postoperative pneumonia can be a fatal complication that may occur after lung resection in cancer patients. Some reports have shown that the incidence of postoperative pneumonia is decreased after esophageal surgery by perioperative oral care; however, there exist no data to suggest that a lack of perioperative oral care can be a risk factor for postoperative pneumonia after lung resection. To investigate the association between the preventive effect of oral care and postoperative pneumonia, we conducted a multicenter, retrospective study of lung cancer patients who underwent lung resection. METHODS: Between January 2014 and December 2016, a total of 721 patients underwent lung resections at 1 of the 6 hospitals included in our study. Among 721 patients, 280 (38.8%) received perioperative oral care, and the remaining 441 (61.2%) did not receive any such care. Propensity score matching was performed to minimize selection biases associated with the comparison of retrospective data between the oral care and control groups. RESULTS: Of the 721 patients, 54 (7.5%) experienced postoperative pneumonia involving 13 of the 280 patients (4.6%) in the oral care group and 41 of the 441 patients (9.3%) in the control group (P = .02). On propensity score analysis, a significant difference was also found between oral care intervention and incidence of postoperative pneumonia (P = .002). CONCLUSION: Our results suggest that perioperative oral care is an effective method to decrease the occurrence of postoperative pneumonia in patients who have undergone lung resection.
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Higiene Bucal , Atención Perioperativa/métodos , Neumonectomía/efectos adversos , Neumonía/epidemiología , Complicaciones Posoperatorias/epidemiología , Anciano , Femenino , Humanos , Neoplasias Pulmonares/cirugía , Masculino , Persona de Mediana Edad , Neumonía/etiología , Neumonía/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
The aim of this study was to investigate the effectiveness of oral care in prevention of postoperative pneumonia associated with esophageal cancer surgery.Postoperative pneumonia is a severe adverse event associated with esophageal cancer surgery. It is thought to be caused by aspiration of oropharyngeal fluid containing pathogens. However, the relationship between oral health status and postoperative pneumonia has not been well investigated.This study included 539 patients with esophageal cancer undergoing surgery at 1 of 7 university hospitals. While 306 patients received perioperative oral care, 233 did not. Various clinical factors as well as occurrence of postoperative pneumonia were retrospectively evaluated. Propensity-score matching was performed to minimize selection biases associated with comparison of retrospective data between the oral care and control groups. Factors related to postoperative pneumonia were analyzed by logistic regression analysis.Of the original 539 patients, 103 (19.1%) experienced postoperative pneumonia. The results of multivariate analysis of the 420 propensity score-matched patients revealed longer operation time, postoperative dysphagia, and lack of oral care intervention to be significantly correlated with postoperative pneumonia.The present findings demonstrate that perioperative oral care can reduce the risk of postoperative pneumonia in patients undergoing esophageal cancer surgery.
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Atención Odontológica/métodos , Neoplasias Esofágicas/cirugía , Atención Perioperativa/métodos , Neumonía/prevención & control , Complicaciones Posoperatorias/prevención & control , Anciano , Estudios de Casos y Controles , Trastornos de Deglución/prevención & control , Hospitales Universitarios , Humanos , Persona de Mediana Edad , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event that may inhibit the treatment of primary disease and remarkably influence the patient's quality of life. The treatment methods for MRONJ, nonsurgical and surgical, are controversial, with no agreement as to which method provides the best outcome and should therefore be recommended. This multicenter retrospective study aimed to investigate the treatment methods and outcome in a large number of patients with MRONJ in Japan, utilizing propensity score matching analysis. A total of 361 patients with MRONJ, at eight hospitals, were registered in this study retrospectively. Various demographic and treatment-related variables were examined and analyzed to determine their correlation with the treatment outcome. After propensity score matching for treatment methods (nonsurgical versus surgical treatment), 176 patients were analyzed by logistic regression. It was shown that those with low-dose administration of an antiresorptive agent and surgical treatment had better outcomes. Furthermore, in 159 patients who underwent surgical treatment, those who underwent extensive surgery experienced significantly better treatment outcomes than those who underwent conservative surgery. This is the first study to compare treatment methods for MRONJ using propensity score matching analysis. The results indicated that extensive surgical treatment should be performed as first-choice therapy for patients with MRONJ. © 2017 American Society for Bone and Mineral Research.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos/cirugía , Puntaje de Propensión , Anciano , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Femenino , Humanos , Masculino , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
The prognosis for patients with advanced esophageal or head-and-neck squamous cell carcinoma (ESCC or HNSCC) remains poor, and the identification of additional oncogenes and their inhibitors is needed. In this study, we evaluated the sensitivities of several ESCC and HNSCC cell lines to HER inhibitors (cetuximab, erlotinib, and afatinib) in vitro and found two cell lines that were hypersensitive to afatinib. Sequence analyses for the afatinib-targeted HER family genes in the two cell lines revealed that one cell line had a previously reported activating EGFR L861Q mutation, whereas the other had an HER4 G1109C mutation of unknown function. No amplification of HER family genes was found in either of the two cell lines. The phosphorylation level of HER4 was elevated in the HER4 G1109C mutation-overexpressed HEK293 cell line, and the mutation had a transforming potential and exhibited tumorigenicity in an NIH3T3 cell line, indicating that this HER4 mutation was an activating oncogenic mutation. Afatinib dramatically reduced the phosphorylation level of EGFR or HER4 and induced apoptosis in the two cell lines. In vivo, tumor growth was also dramatically decreased by afatinib. In a database, the frequencies of HER family gene mutations in ESCC or HNSCC ranged from 0% to 5%. In particular, HER4 mutations have been found relatively frequently in HNSCC. Considering the addiction of cancer cells to activating oncogenic EGFR or HER4 mutations for proliferation, HNSCC or ESCC with such oncogenic mutations might be suitable for targeted therapy with afatinib. Mol Cancer Ther; 15(8); 1988-97. ©2016 AACR.
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Antineoplásicos/farmacología , Carcinoma de Células Escamosas/genética , Transformación Celular Neoplásica/genética , Neoplasias Esofágicas/genética , Neoplasias de Cabeza y Cuello/genética , Mutación , Quinazolinas/farmacología , Receptor ErbB-4/genética , Afatinib , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Receptores ErbB/genética , Receptores ErbB/metabolismo , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Femenino , Células HEK293 , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Ratones , Familia de Multigenes , Células 3T3 NIH , Fosforilación , Receptor ErbB-4/metabolismo , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas de Cabeza y Cuello , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Ameloblastoma with bone formation is rare. We report a case of a 55-year-old woman with ameloblastoma accompanied by prominent osteoplasia. Histopathological examination exhibited an abundant stromal component between tumor nests. Therefore, she was diagnosed as the desmoplastic variant, except for the numerous bone trabeculae. The distinction between new bone formation and invasion of the bone marrow poses a problem. A thin rim of fibrous bone that can be accentuated by Masson-trichrome staining suggests the former.
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Ameloblastoma/patología , Neoplasias Mandibulares/patología , Osificación Heterotópica/patología , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana Edad , Osteoblastos/patologíaAsunto(s)
Artritis Infecciosa/inducido químicamente , Conservadores de la Densidad Ósea/efectos adversos , Neoplasias Óseas/secundario , Difosfonatos/efectos adversos , Imidazoles/efectos adversos , Trastornos de la Articulación Temporomandibular/inducido químicamente , Anciano , Antineoplásicos/efectos adversos , Artritis Infecciosa/complicaciones , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/microbiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/complicaciones , Neoplasias Óseas/tratamiento farmacológico , Resistencia a Medicamentos , Farmacorresistencia Bacteriana Múltiple , Humanos , Masculino , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/tratamiento farmacológico , Trastornos de la Articulación Temporomandibular/microbiología , Irrigación Terapéutica , Estreptococos Viridans , Ácido ZoledrónicoAsunto(s)
Adenolinfoma/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Metástasis Linfática/diagnóstico por imagen , Neoplasias Mandibulares/diagnóstico por imagen , Neoplasias Primarias Múltiples/diagnóstico por imagen , Neoplasias de la Parótida/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Tomografía Computarizada por Rayos X/métodos , Anciano , Carcinoma de Células Escamosas/secundario , Diagnóstico Diferencial , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Radiografía PanorámicaRESUMEN
We have previously reported that Monad, a novel WD40 repeat protein, potentiates apoptosis induced by tumor necrosis factor-alpha and cycloheximide. By affinity purification and mass spectrometry, RNA polymerase II-associated protein 3 (RPAP3) was identified as a Monad binding protein and may function with Monad as a novel modulator of apoptosis pathways. Here we report that Reptin, a highly conserved AAA + ATPase that is part of various chromatin-remodeling complexes, is also involved in the association of RPAP3 by immunoprecipitation and confocal microscopic analysis. Overexpression of RPAP3 induced HEK293 cells to death after UV-irradiation. Loss of RPAP3 by RNAi improved HeLa cell survival after UV-induced DNA damage and attenuated the phosphorylation of H2AX. Depletion of Reptin reduced cell survival and facilitated the phosphorylation on H2AX. These results suggest that RPAP3 modulates UV-induced DNA damage by regulating H2AX phosphorylation.
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Proteínas Portadoras/metabolismo , Daño del ADN , ADN Helicasas/metabolismo , Histonas/metabolismo , Rayos Ultravioleta , ATPasas Asociadas con Actividades Celulares Diversas , Proteínas Reguladoras de la Apoptosis , Proteínas Portadoras/fisiología , Muerte Celular/efectos de la radiación , Línea Celular , ADN Helicasas/fisiología , Humanos , FosforilaciónRESUMEN
We have previously reported that Monad, a novel WD40 repeat protein, potentiates apoptosis induced by tumor necrosis factor-alpha(TNF-alpha) and cycloheximide (CHX). By affinity purification and mass spectrometry, we identified RNA polymerase II-associated protein 3 (RPAP3) as a binding protein of Monad. Overexpression of RPAP3 in HEK 293 potentiated caspase-3 activation and apoptosis induced by TNF-alpha and CHX. In addition, knockdown of RPAP3 by RNA interference resulted in a significant reduction of apoptosis induced by TNF-alpha and CHX in HEK293 and HeLa cells. These results raise the possibility that RPAP3, together with Monad, may function as a novel modulator of apoptosis pathway.
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Proteínas Reguladoras de la Apoptosis/metabolismo , Apoptosis , Proteínas Portadoras/fisiología , Secuencia de Aminoácidos , Proteínas Portadoras/química , Proteínas Portadoras/genética , Línea Celular , Clonación Molecular , Humanos , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , ARN Mensajero/metabolismo , Secuencias Repetitivas de Aminoácido , Distribución TisularRESUMEN
Cancer invasion and metastasis are highly complex processes and a serine protease urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been postulated to play a central role in the mediation of cancer progression. Of note, malignant tumor urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor levels have been found to vary considerably, and to be related to patient prognosis. In mouse models, the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system has been studied extensively as a target for anticancer therapy using a variety of approaches. In this review, we discuss the advances in the various modalities that have been used to target the urokinase-type plasminogen activator/urokinase-type plasminogen activator receptor system, including protein-based and peptide-based drugs, antisense therapy, and RNA interference technology. In particular, preclinical mouse model studies that used human tumor xenografts are reviewed.
Asunto(s)
Neoplasias/terapia , Receptores de Superficie Celular/genética , Activador de Plasminógeno de Tipo Uroquinasa/genética , Animales , Antineoplásicos/farmacología , Elementos sin Sentido (Genética)/uso terapéutico , Sistemas de Liberación de Medicamentos , Marcación de Gen , Terapia Genética/métodos , Humanos , Ratones , Modelos Biológicos , Interferencia de ARN , Receptores de Superficie Celular/antagonistas & inhibidores , Receptores del Activador de Plasminógeno Tipo Uroquinasa , Transducción de Señal , Activador de Plasminógeno de Tipo Uroquinasa/antagonistas & inhibidoresRESUMEN
There have been reports of strong correlations between poor prognosis in various cancers and concomitant expression of urokinase-type plasminogen activator (uPA) and its surface receptor (uPAR). We and others have previously shown that the uPA system plays a significant role in a subset of head and neck squamous cell carcinoma. In the present study, we found that uPAR is required for invasion and metastasis of highly malignant oral cancer cells (OSC-19). Treating OSC-19 cells with antisense oligonucleotides (AS) targeting uPAR resulted in a dramatic decrease of uPAR mRNA expression. Furthermore, pretreatment with AS or siRNA targeting uPAR inhibited progression of OSC-19 cells in experimental models. These results suggest that overexpression of uPAR increases the invasiveness and metastasis of OSC-19 cells, and that uPAR is a promising therapeutic target for regulation of progression of oral cancer.