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1.
Biopreserv Biobank ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38526566

RESUMO

Background: The population of blast cells among peripheral blood mononuclear cells (PBMCs) obtained from patients is a desirable specimen for analyzing gene expression in diseases including acute myeloid leukemia. Although the enrichment of blast cells often needs to be performed at a central laboratory, acceptable conditions for sample transport from clinical sites remain to be established. Methods: We evaluated storage temperature, duration, and tube type before initiating sample processing for the analysis of cluster of differentiation (CD)33+ myeloid cells among PBMCs as an alternative to CD34+/CD33+ blast cells. Results: CD33+ myeloid cells were successfully purified by MACS. The cell viability and the RNA integrity were sustained during storage up to 48 hours before sample processing. Storage at 4°C had minimal effects on gene expression, whereas storage at room temperature induced the senescence pathway, characterized by the expression of stress-inducible genes. A CPT tube was also better than an ethylenediaminetetraacetic acid tube for minimizing gene expression change. Conclusions: Our study provided important clues for establishing a sample handling approach for gene expression analysis with purified cell fractions from human PBMCs. To keep the variation of gene expression to a minimum, samples should be delivered at 4°C within 48 hours before processing.

2.
Head Neck Pathol ; 18(1): 13, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393494

RESUMO

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) are rare tumors recently characterized by the presence of both neuroendocrine and non-neuroendocrine components within the same tumor tissue. Although MiNEN found their place in the WHO classification for various organs, this composite tumor in the head and neck region remains exceptionally rare. We present a case of primary oral MiNEN in a 64-year-old male located on the left side of lower gingiva. Biopsy raised suspicion of neuroendocrine carcinoma (NEC) and the patient underwent partial mandibulectomy. The resected specimen showed two distinct components of NEC and squamous cell carcinoma (SCC) with the confirmation of immunohistochemical markers. There has been no sign of recurrence nor metastasis 6 years after the surgery. In addition, we have conducted a review of published cases with potential relevance to this entity, resulting in five cases. The diverse terminology reinforces the need for a standardized classification system of oral/head and neck MiNENs.


Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Escamosas , Tumores Neuroendócrinos , Masculino , Humanos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Escamosas/patologia , Pescoço/patologia
3.
BMC Oral Health ; 23(1): 595, 2023 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-37633917

RESUMO

BACKGROUND: The development of synchronous multiple primary cancers is one of the major causes of death in patients with head and neck cancer. Herein, we report a case of synchronous intraductal papillary mucinous carcinoma (IPMC), invasive in a patient with maxillary gingival carcinoma. CASE PRESENTATION: A 73-year-old female visited our hospital complaining of a mass on the left side of the maxillary gingiva. Intraorally, an exophytic tumor, 50 × 25 mm in size, was found on the gingiva of the left maxillary posterior, and a diagnosis of squamous cell carcinoma was revealed by cytology. Emission tomography/ computed tomography with 18 Fluorodeoxyglucose-Positron (18FDG- PET/ CT) showed increased accumulation in the left maxillary gingiva, the left side of cervical lymph nodes, and the main pancreatic duct. The pancreatic ductal tumor was performed the biopsy at esophagogastroduodenoscopy (EGD) and resulted in a pathological diagnosis of IPMC, invasive. The patient was diagnosed as synchronous double primary cancers consisting of maxillary gingival carcinoma cT4aN2bM0 and IPMC, invasive cT3N0M0. She refused radical treatment, and died 11 months later. CONCLUSION: 18FDG- PET/ CT, EGD and multidisciplinary approach is required for the detection and determining the treatment strategy of synchronous double primary cancers.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma de Células Escamosas , Neoplasias Gengivais , Feminino , Humanos , Idoso , Fluordesoxiglucose F18 , Gengiva , Adenocarcinoma Mucinoso/diagnóstico por imagem
4.
Int J Surg Case Rep ; 98: 107499, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36037640

RESUMO

INTRODUCTION AND IMPORTANCE: Pulmonary pleomorphic carcinoma (PPC) is a rare subtype of non-small cell lung cancer. No standard therapy has been established for advanced disease, which results in poor prognosis. Some cases of PPC metastasizing to mandibular gingiva have been reported, and the involved site in these reports is all unilateral mandible. CASE PRESENTATION: We report a case of PPC metastasizing to the anterior mandibular gingiva in a 68-year-old man. The patient was referred to our hospital with tumor bleeding and difficulty with intake. One month before, he had been diagnosed as PPC. The size of oral tumor was 28 × 25 mm, and we performed surgical resection. Although there was no recurrence of oral lesion, he died of systemic metastases after 3 months since the surgery. CLINICAL DISCUSSION: The prognosis of patients with metastatic tumor in oral region is poor. Radical treatment for oral lesion is often difficult due to the existence of other metastasis or the refractory, in particular cases with high grade malignancies such as PPC. On the other hand, because of the development of cancer treatment and the arrival of super-aging society, the number of patients with metastatic tumor in oral region has been expected to increase in future. CONCLUSION: PPC metastasizing to the gingiva of mandibular symphysis is extremely rare. If there are possibilities to improve the prognosis or quality of life, radical or palliative treatment for metastatic tumor in oral region should be performed.

5.
Cureus ; 14(4): e24171, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35463557

RESUMO

Nasotracheal intubation is generally used in maxillofacial and oral surgeries under general anesthesia. However, nasal intubation may cause various complications including epistaxis, retropharyngeal dissection, and intracranial penetration of the nasotracheal tube, which occurs in patients with basal skull defects or fractures. Therefore, nasotracheal intubation is usually contraindicated in such patients. Herein, we describe an alternative technique using a balloon catheter in nasotracheal intubation to avoid surgical airway management in a patient with a history of transsphenoidal surgery. The use of a balloon catheter may be a simple and safe method of nasotracheal intubation in patients with basal skull defects.

6.
Oral Oncol ; 120: 105453, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34265573

RESUMO

OBJECTIVES: To evaluate the ability of different imaging modalities to accurately detect bone invasion in oral squamous cell carcinomas. PATIENTS AND METHODS: Patients with oral squamous cell carcinoma, who were scheduled for mandibulectomy or maxillectomy, underwent clinical evaluation using five preoperative imaging diagnosis methods-contrast-enhanced MRI, CT, 99mTc scintigraphy (Tc scan), FDG-PET CT (PET/CT), and panoramic radiography. The sensitivity and specificity of each modality in detecting bone invasion were calculated by comparing the findings on the images with postoperative histopathological findings. In a subgroup of patients, we further assessed the ability of MRI and CT to detect the accurate extent of bone invasion, including the height, width, and depth in patients with pathological mandibular invasion. RESULTS: Overall, 50 patients were enrolled in this study, and nine patients with pathological mandibular invasion were included in our subgroup analysis. MRI was found to be the most useful method in detecting bone invasion, showing the highest sensitivity (88.9%) and negative predictive values (92.3%). CT (87.5% specificity and 77.8% sensitivity) was more specific than MRI, though less sensitive. Combined PET/CT was more sensitive (83.3%) and less specific (71.9%) than CT. Tc scan had high sensitivity (88.9%); however, the specificity was relatively low (71.9%). CONCLUSION: MRI was the most useful method in detecting bone invasion. A negative MRI result definitively excludes bone marrow invasion. In patients with positive MRI findings, a negative CT may be useful in ruling out bone marrow invasion.


Assuntos
Mandíbula/patologia , Neoplasias Bucais , Invasividade Neoplásica/diagnóstico por imagem , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fluordesoxiglucose F18 , Humanos , Imageamento por Ressonância Magnética , Neoplasias Bucais/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico por imagem , Tomografia Computadorizada por Raios X
7.
Auris Nasus Larynx ; 48(5): 1007-1012, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33824036

RESUMO

OBJECTIVE: Computer-aided design and computer-aided manufacturing (CAD/CAM) techniques are increasingly applied to mandibular reconstruction, but the superiority of this method in oral food intake has not been well established. Considering the extent of mandibular defects, this retrospective study was aimed to clarify the impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer. MATERIALS AND METHODS: We performed a retrospective review of 50 patients who had undergone segmental mandibulectomy with free flap reconstruction for locally advanced oral cancer. The patients' Functional Oral Intake Scale scores were measured at 3 months after surgery, and possible contributing factors including CAD/CAM mandibular reconstruction and the extent of mandibular defects for oral food intake were subjected to univariate analysis and multivariate logistic regression analysis. RESULTS: Multivariate logistic regression analysis showed that CAD/CAM mandibular reconstruction was independently associated with good oral intake, whereas both anterior or extensive mandibular resection and glossectomy were also independently associated with poor oral intake after surgery. CONCLUSION: The present study showed the positive impact of CAD/CAM mandibular reconstruction on chewing and swallowing function after surgery for locally advanced oral cancer for the first time.


Assuntos
Transplante Ósseo/métodos , Desenho Assistido por Computador , Fíbula/transplante , Osteotomia Mandibular/métodos , Reconstrução Mandibular/métodos , Neoplasias Bucais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Idoso , Deglutição/fisiologia , Ingestão de Alimentos , Feminino , Retalhos de Tecido Biológico , Humanos , Imageamento Tridimensional , Modelos Logísticos , Masculino , Mastigação/fisiologia , Neoplasias Bucais/patologia , Análise Multivariada , Estudos Retrospectivos , Escápula/transplante
8.
Transfus Apher Sci ; 60(4): 103144, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33893027

RESUMO

Fibrin glue from autologous plasma may prevent viral infection and allergic reaction. Moreover, this biomaterial contains growth factors such as TGF-ß and VEGF that promote reconstruction of the mucous membrane by stimulating fibroblast proliferation and angiogenesis. Thus, autologous fibrin glue is predicted to improve healing better than commercial fibrin glue. Here, we evaluated the effects of autologous fibrin glue on the crucial early phase of wound healing. Epithelial defects were introduced in rats and covered with polyglycolic acid (PGA) sheets with or without commercial or autologous fibrin glue. Wound healing was assessed for six weeks by histology and immunohistochemistry. Our results demonstrate that wounds covered with PGA sheets and autologous fibrin glue achieved efficient wound healing without complications such as local infection or incomplete healing. The rate of recovery of the regenerating epithelium in this group was superior to that in wounds covered with PGA sheets and commercial fibrin glue. Immunohistochemistry of laminin, cytokeratin, and VEGF confirmed fine and rapid epithelial neogenesis. Collectively, our results indicate that covering surgical wounds with autologous fibrin glue promotes wound healing and epithelialization, improves safety, and reduces the risks of viral infection and allergic reaction associated with conventional techniques.


Assuntos
Adesivo Tecidual de Fibrina/farmacologia , Ácido Poliglicólico/farmacologia , Pele/lesões , Cicatrização/efeitos dos fármacos , Ferimentos e Lesões/terapia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Ferimentos e Lesões/metabolismo
9.
Int J Clin Exp Pathol ; 13(7): 1633-1639, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32782682

RESUMO

Global standard fractionated radiotherapy (RT) for the treatment of malignancies consists of X-ray irradiation with 2-Gy/day, 5 days a week for 5-7 weeks. Recently, clinically relevant radioresistant (CRR) cells were first defined as cells that can continue to grow even after exposure to daily 2-Gy of X-rays for more than 30 days in vitro. To analyze the characteristics of radioresistant cancer cells, CRR oral cancer cells (CRR-OCCs) were established, and the expression level of interferon-stimulated exonuclease gene 20 (ISG20) was evaluated with qRT-PCR and immunohistochemical analysis. Our result revealed that the expression level of both ISG20 mRNA and its protein in CRR-OCCs were higher than those of corresponding parental cells. We concluded that ISG20 was statistically overexpressed in CRR-OCCs. ISG20 overexpression may be necessary for the radioresistant phenotype in CRR-OCCs, and targeting ISG20 of human cancer cells may lead to more efficient RT or chemoradiotherapy for eliminating cancer.

10.
Ann Nucl Med ; 34(9): 643-652, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32564300

RESUMO

OBJECTIVE: A positron emission tomography (PET) scanner using a silicon photomultiplier (SiPM PET) in place of a photomultiplier tube significantly improves the spatial and time resolution. It may also improve the evaluation of smaller lesions compared to conventional (non-SiPM) PET scanners. We compared the maximum standardized uptake value (SUVmax), detection sensitivity, and morphological correlation using magnetic resonance imaging (MRI) for primary tongue squamous cell carcinoma between the SiPM PET and non-SiPM PET scanner. METHODS: We retrospectively reviewed the F-18 fluorodeoxyglucose (FDG) PET/CT features of tongue squamous cell carcinomas in consecutive, newly diagnosed, and pathologically verified patients. Twenty-five of 46 patients were scanned using SiPM PET scanner and the remaining 21 patients were scanned with a non-SiPM PET scanner. We compared the SUVmax and visual evaluation of primary tumor detectability, and the correlation between the PET-based and MRI-based tumor size (long axis, thickness, and volume). Differences in SUVmax and detection sensitivity for the primary tumor were analyzed using Welch's t test and Fisher's exact test, respectively. Correlations among the PET-based, MRI-based tumor size, and SUVmax were assessed using Spearman's rank correlation coefficient. RESULTS: SUVmax of both T1/T2 and T3/T4 primary tumors were significantly higher for the SiPM PET (T1/T2 mean SUVmax: 6.6 ± 4.3, T3/T4 mean SUVmax: 18.2 ± 9.8) than that for the non-SiPM PET (T1/T2 mean SUVmax: 3.4 ± 1.4, T3/T4 mean SUVmax: 10.2 ± 4.9) (P < 0.05). While all cases of T3/T4 primary tumors were detected by both PET scanners, the detection sensitivity for T1/T2 primary tumors was significantly higher for the SiPM PET (80%) than that for the non-SiPM PET (36.4%) (P < 0.05). MRI-based tumor size correlated significantly with SiPM PET-based tumor long axis (ρ = 0.74) and volume (ρ = 0.91), but not with the non-SiPM PET-based tumor long axis and volume in T1/T2 primary lesions. Correlation between MRI-based tumor size and SUVmax was significant in both PET scanners; however, no significant difference was observed between the two scanners. CONCLUSIONS: The SiPM PET provides better detection sensitivity and a reliable morphological correlation for the T1/T2 primary tongue tumors than the non-SiPM PET due to its high performance.


Assuntos
Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/instrumentação , Silício , Neoplasias da Língua/diagnóstico por imagem , Neoplasias da Língua/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Adulto Jovem
11.
J Oral Sci ; 61(3): 406-411, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31341120

RESUMO

Oral rehabilitation with prosthodontic treatment considerably influences the well-being and quality of life of patients after ablative oral tumor surgery. This study evaluated the effects of implant-supported prostheses (ISPs) on oral health-related quality of life (OHRQoL) and chewing ability in 10 patients who requested ISPs after mandibular oral tumor resection. OHRQoL was assessed using the Japanese version of the Oral Health Impact Profile (OHIP-49) before and one year after ISP placement. Chewing ability, including self-assessed masticatory ability and occlusal force, was examined at one year after ISP placement. The initial mean total OHIP-49 score of 65.3 ± 9.79 decreased to 46.0 ± 8.14 at one year after ISP placement. Mean OHIP-49 score decreased in all domains, whereas self-assessed masticatory ability increased within one year of ISP placement. There were no significant differences between prosthesis types with respect to the mean OHIP-49 score or self-assessed masticatory ability. In conclusion, ISP placement improves OHRQoL and the self-assessed masticatory ability. Moreover, the prosthesis type might not significantly affect OHRQoL.


Assuntos
Implantes Dentários , Neoplasias Mandibulares , Humanos , Mandíbula , Saúde Bucal , Qualidade de Vida , Inquéritos e Questionários
12.
J Pain Res ; 12: 377-385, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30705603

RESUMO

PURPOSE: Remifentanil is associated with acute opioid tolerance that can lead to increased postoperative consumption of opioid analgesics. The purpose of this study was to determine whether a low dose of ketamine prevents remifentanil-induced acute opioid tolerance and affects the neutrophil-lymphocyte ratio (NLR), a newly recognized biomarker of inflammation. MATERIALS AND METHODS: Forty patients undergoing orthognathic surgery were enrolled in this prospective, randomized, double-blind study and randomly assigned to intraoperative administration of one of the following anesthetic regimens: high-dose remifentanil (0.6 µg/kg/minute); low-dose remifentanil (0.2 µg/kg/minute); or high-dose remifentanil with ketamine (remifentanil 0.6 µg/kg/minute with 0.5 mg/kg ketamine just after induction followed by an intraoperative infusion of ketamine 5 µg/kg/minute until wound closure). Fentanyl by intravenous patient-controlled analgesia was used for postoperative pain control. Visual Analog Scale pain scores and fentanyl consumption were recorded in the first 24 hours postoperatively. Perioperative serum C-reactive protein level and NLR were also determined. RESULTS: Baseline characteristics were similar in the three study groups. There were no between-group differences in Visual Analog Scale pain scores during the study period. The high-dose remifentanil group had a significantly higher requirement for fentanyl than the other two groups. Addition of ketamine did not affect the C-reactive protein level but increased the NLR; this increase was associated with decreased fentanyl consumption. CONCLUSION: High-dose intraoperative remifentanil induced postoperative acute opioid tolerance that was prevented by infusion of low-dose ketamine. Ketamine increased the postoperative NLR associated with decreased fentanyl requirement for postoperative pain control.

13.
Anesth Prog ; 66(4): 211-217, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31891291

RESUMO

Epistaxis is one of the most common complications of nasotracheal intubation and can be life-threatening. However, there is little discussion in the current literature on the acute management of massive epistaxis after nasotracheal extubation. This is a report of 2 patients who experienced severe unanticipated nasal bleeding immediately after extubation, 1 after a surgical procedure for oral cancer and another after restorative dental treatment. In both cases the significant epistaxis was managed successfully with a Foley balloon catheter used to pack the posterior nasal cavity. The Foley catheter technique may be useful for managing and arresting sudden postextubation epistaxis.


Assuntos
Extubação , Epistaxe , Laringoscópios , Adulto , Idoso , Extubação/efeitos adversos , Reparação de Restauração Dentária , Epistaxe/etiologia , Epistaxe/terapia , Feminino , Humanos , Intubação Intratraqueal , Masculino , Neoplasias Bucais/cirurgia , Cavidade Nasal
14.
J Craniofac Surg ; 29(7): e713-e717, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30192292

RESUMO

INTRODUCTION: The relationship between impacted mandibular third molars with angle and condylar fractures is subject of many publications, yet their conclusions differ widely, hence the authors wanted to investigate this topic in their patients. METHODS: The authors designed a retrospective study including 241 patients who presented with angle and/or mandibular condyle fractures over a 13-year period at the authors' institution. The study variable was the presence/absence of third molars. The authors used the Pell and Gregory system to classify their position, whereas the angulation was classified using Archer classification. The outcome variables were the presence of angle and condylar fractures. Other study variables included fracture etiology. RESULTS: Assaults were the most frequent cause of angle fractures (62.7%), whereas falls were mostly responsible for condylar fractures (79.6%). Angle fractures were mostly isolated (66.3%), whereas condylar fractures were mostly associated with other fractures (62.6%). The majority of the angle fractures occurred in patients with third molars (63.6%), on the contrary the majority of the condylar fractures occurred in patients without mandibular third molars (78.3%). Angle fractures were mostly associated with fully erupted or superficially impacted third molars (90,9%). Finally in the presence of mesioangulated third molars, condylar fractures did not happen in 83.8% of patients. CONCLUSIONS: According to the authors' findings, fully erupted or superficially impacted mandibular third molars are a risk factor for angle fractures but at the same time a protective factor for the condyle. On the contrary, the absence of mandibular third molars "strengthens" the angle and represents a risk factor for condylar fractures.


Assuntos
Côndilo Mandibular/lesões , Fraturas Mandibulares/epidemiologia , Dente Serotino , Adolescente , Adulto , Feminino , Humanos , Masculino , Fraturas Mandibulares/etiologia , Pessoa de Meia-Idade , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Erupção Dentária , Dente Impactado/complicações , Dente Impactado/epidemiologia , Adulto Jovem
15.
J Craniomaxillofac Surg ; 45(9): 1458-1463, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28689686

RESUMO

The CryoSeal® FS System has been recently introduced as an automated device for the production of complete fibrin glue from autologous plasma, rather than from pool allogenic or cattle blood, to prevent viral infection and allergic reaction. We evaluated the effectiveness of complete autologous fibrin glue and polyglycolic acid (PGA) sheet wound coverings in mucosa defect oral surgery. Postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding were evaluated in 12 patients who underwent oral (including the tongue) mucosa excision, and received a PGA sheet and an autologous fibrin glue covering. They were compared with 12 patients who received a PGA sheet and commercial allogenic fibrin glue. All cases in the complete autologous fibrin glue group demonstrated good wound healing without complications such as local infection or incomplete cure. All evaluated clinical measures in this group were similar or superior to the commercial allogenic fibrin glue group. Coagulation and adhesion quality achieved with this method was comparable to that with a PGA sheet and commercial fibrin glue. Covering oral surgery wounds with complete autologous fibrin glue produced by an automated device was convenient, safe, and reduced the risk of viral infection and allergic reaction associated with conventional techniques.


Assuntos
Bandagens , Adesivo Tecidual de Fibrina , Doenças da Boca/cirurgia , Boca/cirurgia , Ácido Poliglicólico , Adesivos Teciduais , Cicatrização , Autoenxertos , Curativos Biológicos , Humanos , Mucosa Bucal/cirurgia , Neoplasias Bucais/cirurgia , Procedimentos Cirúrgicos Bucais , Lesões Pré-Cancerosas/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Língua/cirurgia
16.
Exp Ther Med ; 13(1): 247-253, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28123497

RESUMO

Investigation of cyclooxygenase (COX)-2 in dentigerous cyst and ameloblastoma may help to improve understanding of the nature and behavior of odontogenic cysts and tumors, and in addition may eventually represent a definitive target for a pharmacological approach in the management of these lesions. The aim of this study was to evaluate COX-2 expression and its correlation with the proliferation of odontogenic epithelium in these lesions. Dentigerous cysts (n=16) and ameloblastomas (n=17) were evaluated. Detection of Ki-67 and COX-2 protein expression was conducted by immunohistochemistry. Data were statistically analyzed using Mann-Whitney U test and Spearman's rank correlation coefficient. No significant differences were found in the expression of Ki-67 and COX-2 between dentigerous cysts and ameloblastomas (P>0.05). A significant positive correlation (P=0.018) and highly significant positive correlation (P=0.004) were found between Ki-67 and COX-2 expression in the odontogenic epithelium of dentigerous cyst and ameloblastoma, respectively. COX-2 was expressed in the odontogenic epithelium of dentigerous cyst and ameloblastoma. It may contribute to local extension of these lesions by increasing the proliferation of their odontogenic epithelial cells.

17.
Biochem Biophys Res Commun ; 488(4): 648-654, 2017 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-28087278

RESUMO

Protein translation is highly activated in cancer tissues through oncogenic mutations and amplifications, and this can support survival and aberrant proliferation. Therefore, blocking translation could be a promising way to block cancer progression. The process of charging a cognate amino acid to tRNA, a crucial step in protein synthesis, is mediated by tRNA synthetases such as prolyl tRNA synthetase (PRS). Interestingly, unlike pan-translation inhibitors, we demonstrated that a novel small molecule PRS inhibitor (T-3861174) induced cell death in several tumor cell lines including SK-MEL-2 without complete suppression of translation. Additionally, our findings indicated that T-3861174-induced cell death was caused by activation of the GCN2-ATF4 pathway. Furthermore, the PRS inhibitor exhibited significant anti-tumor activity in several xenograft models without severe body weight losses. These results indicate that PRS is a druggable target, and suggest that T-3861174 is a potential therapeutic agent for cancer therapy.


Assuntos
Fator 4 Ativador da Transcrição/metabolismo , Aminoacil-tRNA Sintetases/antagonistas & inibidores , Antineoplásicos/farmacologia , Inibidores Enzimáticos/farmacologia , Ácidos Picolínicos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Pirrolidinonas/farmacologia , Aminoacil-tRNA Sintetases/metabolismo , Animais , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Ácidos Picolínicos/química , Pirrolidinonas/química , Relação Estrutura-Atividade
18.
Mol Cancer Ther ; 16(2): 273-284, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27903753

RESUMO

Dysregulation of lysine (K)-specific demethylase 1A (LSD1), also known as KDM1A, has been implicated in the development of various cancers, including leukemia. Here, we describe the antileukemic activity and mechanism of action of T-3775440, a novel irreversible LSD1 inhibitor. Cell growth analysis of leukemia cell lines revealed that acute erythroid leukemia (AEL) and acute megakaryoblastic leukemia cells (AMKL) were highly sensitive to this compound. T-3775440 treatment enforced transdifferentiation of erythroid/megakaryocytic lineages into granulomonocytic-like lineage cells. Mechanistically, T-3775440 disrupted the interaction between LSD1 and growth factor-independent 1B (GFI1B), a transcription factor critical for the differentiation processes of erythroid and megakaryocytic lineage cells. Knockdown of LSD1 and GFI1B recapitulated T-3775440-induced transdifferentiation and cell growth suppression, highlighting the significance of LSD1-GFI1B axis inhibition with regard to the anti-AML effects of T-3775440. Moreover, T-3775440 exhibited significant antitumor efficacy in AEL and AMKL xenograft models. Our findings provide a rationale for evaluating LSD1 inhibitors as potential treatments and indicate a novel mechanism of action against AML, particularly AEL and AMKL. Mol Cancer Ther; 16(2); 273-84. ©2016 AACR.


Assuntos
Antineoplásicos/farmacologia , Transdiferenciação Celular/efeitos dos fármacos , Histona Desmetilases/antagonistas & inibidores , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Complexos Multiproteicos/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras/metabolismo , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Análise por Conglomerados , Biologia Computacional/métodos , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Hematopoese/genética , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Camundongos , Terapia de Alvo Molecular , Ligação Proteica , Proteínas Proto-Oncogênicas/genética , Proteínas Repressoras/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Craniomaxillofac Surg ; 44(8): 964-8, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27341770

RESUMO

Polyglycolic acid (PGA) sheets and commercial fibrin glue are commonly used to cover open wound surfaces in oral surgery. Compared to commercial fibrin glue composed of pooled allogeneic blood, autologous fibrin glue is less expensive and poses lower risks of viral infection and allergic reaction. Here, we evaluated postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding in 24 patients who underwent partial glossectomy plus the application of a PGA sheet and an autologous fibrin glue covering (autologous group) versus 11 patients in whom a PGA sheet and commercial fibrin glue were used (allogeneic group). The evaluated clinical measures were nearly identical in both groups. Remarkable wound surface granulation was recognized in two cases in the autologous group. No complications were observed in either group, including viral infection or allergic reaction. Abnormal postoperative bleeding in the wound region was observed in one case in the allogeneic group. Coagulation and adhesion of the autologous fibrin glue were equivalent to those of conventional therapy with a PGA sheet and commercial fibrin glue. Thus, our results show that covering wounds with autologous fibrin glue and PGA sheets may help avoid the risks of viral infection and allergic reaction in partial glossectomy cases.


Assuntos
Adesivo Tecidual de Fibrina , Glossectomia , Ácido Poliglicólico , Ferida Cirúrgica , Procedimentos Cirúrgicos sem Sutura , Adesivos Teciduais , Adulto , Idoso , Feminino , Glossectomia/efeitos adversos , Glossectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Hemorragia Pós-Operatória
20.
Med Mol Morphol ; 49(2): 76-82, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26439725

RESUMO

The number of people afflicted with oral carcinoma in Japan has increased in recent years. Although preoperative neoadjuvant therapy with cisplatin and 5-fluorouracil are performed, chemotherapeutic response varies widely among the patients. With the aim of establishing novel indices to predict the therapeutic response to chemotherapy, we investigated the relationship between morphological features of pre-treatment oral carcinoma nuclei and the chemotherapeutic response using quantifying morphology of cell nuclei in pathological specimen images. We measured 4 morphological features of the nucleus of oral squamous cell carcinoma cases classified by the response to chemotherapy: No Change (NC) group, Partial Response (PR) group and Complete Response (CR) group. Furthermore, we performed immunohistochemical staining for p53 and Ki67 and calculated their positive rates in cancer tissues. Compactness and symmetry of the nucleus were significantly higher and nuclear edge response was significantly lower in cancer cells with lower chemotherapeutic responses compared high chemotherapeutic responders. As for positive rates of p53 and Ki67, there were no significant differences between any of the response groups. Morphological features of cancer cell nuclei in pathological specimens are sensitive predictive factors for the chemotherapeutic response to oral squamous cell carcinoma.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Forma do Núcleo Celular , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Forma do Núcleo Celular/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo
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