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3.
Int J Oral Maxillofac Surg ; 52(10): 1025-1027, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36935282

RESUMO

Sialendoscopy is a minimally invasive technique used mainly in the diagnosis and treatment of obstructive salivary gland disorders. There has yet to be a report on its use in the diagnosis of metastatic disease. While metastatic cancer has been described in numerous head and neck anatomic subsites, it has not been reported to be found in a mucous plug in Stensen's duct. Sialendoscopy was performed in a 68-year-old female patient who presented with symptoms of ductal obstruction. Basket removal of a mucous plug was done and histopathological analysis of this specimen found adenocarcinoma. The overall clinical picture, imaging, and final histopathological results suggested that this patient had metastatic breast carcinoma to a mucous plug in Stensen's duct, the diagnosis of which was made with the aid of interventional sialendoscopy. This is the first report in which metastatic cancer was identified in a mucous plug in Stensen's duct. Sialendoscopy can be a useful tool to aid in the diagnosis of metastatic diseases in rare and unusual clinical situations.


Assuntos
Adenocarcinoma , Ductos Salivares , Feminino , Humanos , Idoso , Ductos Salivares/diagnóstico por imagem , Ductos Salivares/cirurgia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Endoscopia/métodos
4.
Int J Oral Maxillofac Surg ; 52(8): 839-846, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36653273

RESUMO

A protuberant shape and sufficient volume are the most important parameters for total tongue reconstruction. The conventional pectoralis major myocutaneous (PMMC) flap undergoes collapse due to atrophy of the denervated muscle. In a new technique, this flap was rolled up like sushi to reshape the neotongue. This study explored the feasibility and effect of the 'sushi roll' technique for precise total functional reconstruction of the tongue using a PMMC flap. Thirty patients scheduled for total glossectomy and PMMC flap reconstruction were recruited. The sushi roll technique was performed in 15 patients and the conventional repair in 15 patients. Outcomes were compared between the two groups. The flap survived in all 30 patients. The sushi roll group showed superior results to the conventional group in terms of time to oral alimentation (P = 0.012) and decannulation (P = 0.041), as well as swallowing function (P = 0.032), speech intelligibility (P < 0.001), shape (P < 0.001), and quality of life score (P < 0.001) at 12 months. The innovative sushi roll technique uses a folding method that utilizes the length rather than the thickness and width of the flap to maintain the volume and protuberance of the neotongue, which results in acceptable function and improved quality of life.


Assuntos
Retalho Miocutâneo , Neoplasias da Língua , Humanos , Músculos Peitorais/transplante , Qualidade de Vida , Neoplasias da Língua/cirurgia , Língua/cirurgia , Glossectomia/métodos
5.
Int J Oral Maxillofac Surg ; 51(1): 44-53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33865661

RESUMO

Spatial deviations of the temporomandibular joint (TMJ) after oncological mandibular reconstruction are important to the aesthetic and functional rehabilitation. The aim of this study was to clarify whether and how three dimensionally (3D) printed patient-specific surgical plates, and the preservation of the condyle or ramus, affect spatial deviations of the TMJ. A total of 33 patients who underwent mandibular reconstruction via computer-assisted surgery were included. Regarding absolute deviations, patients in the 3D-printed plate group showed smaller TMJ deviations compared to those in the conventional plate group. There was no difference in absolute deviations of the TMJ regardless of whether the condyle or ramus was preserved. Regarding physiological deviations, the impact on the contralateral TMJ was smaller in the 3D-printed plate group. Patients with both the condyle and ramus removed had significantly higher deviations of the condyle and joint space. In summary, 3D-printed patient-specific surgical plates improved the spatial accuracy of the TMJ. Under physiological conditions, TMJ deviations on the operated side were mainly affected by the preservation of the condyle. Removal of both the condyle and ramus caused more severe spatial interference to the TMJ; this should be further confirmed.


Assuntos
Reconstrução Mandibular , Cirurgia Assistida por Computador , Placas Ósseas , Estética Dentária , Humanos , Côndilo Mandibular , Articulação Temporomandibular
6.
Int J Oral Maxillofac Surg ; 51(7): 886-891, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34920910

RESUMO

The purpose of this study was to investigate whether ameloblastoma with a high likelihood of recurrence can be predicted using random forest model, a machine learning algorithm. Data were collected from patients treated for ameloblastoma between 1999 and 2019 at the University of Hong Kong. Fourteen clinical parameters were used to grow the decision trees to classify patients with or without ameloblastoma recurrence in the follow-up period. The random forest algorithm was computed 100 times in the training cohort (n = 100) and verified in the testing cohort (n = 50). The receiver operating characteristic curve (ROC) and area under the curve (AUC) were used as the performance measurement of separability. One hundred and fifty patients (76 female, 74 male) were recruited, with a mean follow-up time of 103 months. Recurrence occurred in a total of 25 cases (16.7%) over the 20-year period. The AUC were calculated for the median and mean ROC curves; these were 0.777 and 0.825, respectively. The results showed that random forest model was able to predict recurrence of ameloblastoma with reliable accuracy. The four most important variables influencing ameloblastoma recurrence were the time elapsed from treatment, initial surgical treatment, tumour size, and radiographic presentation. This study provides insights into the detection of high-risk patient groups to monitor recurrence. Further application of random forest to other diseases could greatly benefit clinical decisions.


Assuntos
Ameloblastoma , Algoritmos , Ameloblastoma/diagnóstico por imagem , Ameloblastoma/cirurgia , Feminino , Humanos , Aprendizado de Máquina , Masculino
7.
Int J Oral Maxillofac Surg ; 50(7): 933-939, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33168369

RESUMO

The sagittal split ramus osteotomy (SSRO) and intraoral vertical ramus osteotomy (IVRO) are two common orthognathic procedures for the treatment of mandibular prognathism. This randomized clinical trial compared the surgical morbidities between SSRO and IVRO for patients with mandibular prognathism over the first 2 years postoperative. Ninety-eight patients (40 male, 58 female) with a mean age of 24.4±3.5 years underwent bilateral SSRO (98 sides) or IVRO (98 sides) as part or all of their orthognathic surgery. IVRO presented less short-term and long-term surgical morbidity in general. The SSRO group had a greater incidence of inferior alveolar nerve deficit at all follow-up time points (P< 0.01). There was more TMJ pain at 6 weeks (P= 0.047) and 3 months (P= 0.001) postoperative in the SSRO group. The SSRO group also presented more minor complications, which were related to titanium plate exposure and infection. There were no major complications for either technique in this study. Despite the need for intermaxillary fixation, IVRO appears to be associated with less surgical morbidity than SSRO when performed as a mandibular setback procedure to treat mandibular prognathism.


Assuntos
Má Oclusão Classe III de Angle , Prognatismo , Adulto , Feminino , Humanos , Masculino , Mandíbula/cirurgia , Osteotomia Mandibular , Morbidade , Osteotomia Sagital do Ramo Mandibular , Prognatismo/cirurgia , Adulto Jovem
8.
Int J Oral Maxillofac Surg ; 49(12): 1592-1594, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32620451

RESUMO

During sialoendoscopy, insertion of the endoscope through the ductal orifice is usually a challenging procedure, especially for beginners. Based on our experience, we have found that using the Kolenda Salivary Access Introducer Set is the most reliable and easily learned ductal access approach. We report details of the technique and discuss the advantages of this approach.


Assuntos
Ductos Salivares , Endoscopia , Ductos Salivares/diagnóstico por imagem , Ductos Salivares/cirurgia
9.
J Dent Res ; 99(11): 1252-1261, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32527169

RESUMO

Areca nut (AN) chewing contributes to an increase of oral squamous cell carcinoma (OSCC) cases in South and Southeast Asia; however, genomic events underlying the carcinogenesis process of AN-related OSCC remain unclear. Here, we comprehensively describe the genomic and transcriptome alterations of 113 Chinese OSCC patients (89 AN related and 24 AN negative) by whole-exome sequencing and RNA sequencing, and we compared the genomic differences between AN-related and AN-negative samples by integrating sequencing data of 325 OSCC patients from The Cancer Genome Atlas database and 50 from a published Taiwanese study. We identified 11 significantly mutated genes for OSCC, including 4 novel ones (ATG2A, WEE1, DST, and TSC2), of which WEE1 and ATG2A mutated with significantly higher rates in AN-related samples (P = 0.04 and P = 0.003, respectively). Mutational signature analysis revealed that AN-related OSCCs were specially characterized by the genomic signature of mismatch repair deficiency (dMMR), which could also predict the prognosis status of AN-related OSCC. In addition, an elevated PD-L1 expression was also observed in both AN-related patients (P = 3.71 × 10-11) and those with a high dMMR level (P = 1.99 × 10-4). Further differential expression analysis and in vitro experiments confirmed the role of dMMR in the development of OSCC induced by AN exposure. Taken together, this study first revealed the molecular profiles and highlighted the role of dMMR in AN-related OSCC among the Chinese population and identified that AN-related OSCC may represent a potential cohort for effective anti-PD-1/L1 immunotherapy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Areca/efeitos adversos , Neoplasias Encefálicas , Carcinoma de Células Escamosas/genética , Neoplasias Colorretais , Genômica , Humanos , Neoplasias Bucais/genética , Síndromes Neoplásicas Hereditárias , Nozes
10.
Zhonghua Liu Xing Bing Xue Za Zhi ; 41(4): 514-519, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32344474

RESUMO

Objective: To investigate the influence of the prevalence and co-prevalence of risk factors for metabolic syndrome on the scores of different levels of metabolic syndrome in people receiving physical examination in Urumqi. Methods: Using the 2017 Xinjiang Health Examination Database, a total of 175 927 people from 7 districts and 1 county in Urumqi were selected as subjects. Face-to-face survey and body measurements were used to collect cardiovascular risk factors and metabolic syndrome scores. Metabolic syndrome scores were used. For the 0-5 points at 6 levels, χ(2), χ(2) trend test, correlation analysis of ordered variable Kendall's tau-b, and logistic regression analysis of ordered results were used to analyze the influence of prevalence and co-prevalence of behavioral risk factors on the MS scores. Results: The percentages of 6 metabolic syndrome scores in the sample population were 23.82%, 27.87%, 22.41%, 16.03%, 8.02%, and 1.85%, respectively. The scores of metabolic syndrome were different in different age groups, ethnic groups, groups with different drinking rates, and groups with different dietary types, with the differences all significant (P<0.05).The MS score in men increased with the increase of oil/salt rate and excessive drinking rate (P<0.01). The score in women increased with the increase of the current smoking rate, oil/salt rate, and increased with the decrease of physical activity (P≤0.01). There was no significant difference in the distribution of regular drinking rates between different score groups (P>0.05). The scores of metabolic syndrome increased with the increase of risk factors (P<0.05). Ordered results logistic analysis found that in the men with ≥3 risk factors and the metabolic syndrome score was 1.15 (1.06-1.26) times higher than that in the men without risk factor, as well as in women with 2 risk factors and≥3 risk factors. The metabolic syndrome scores were 1.38 (1.22-1.55), 2.02 (1.53-2.66) times higher than those in the women without risk factors. Conclusions: The physical examination group in Urumqi, the more the metabolic syndrome disease behavior risk factors clustered, the higher the metabolic syndrome score was. Therefore, comprehensive intervention measures should be taken to control the different forms of metabolic syndrome to prevent the occurrence and progress of the disease.


Assuntos
Doenças Cardiovasculares/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Povo Asiático , China/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Assunção de Riscos , Fumar/epidemiologia
11.
Int J Oral Maxillofac Surg ; 49(10): 1351-1354, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31982237

RESUMO

Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a benign lymphoproliferative lesion related to iatrogenic or age-related immunosuppression in patients with prior Epstein-Barr virus (EBV) infection. Although the clinical presentation may resemble malignant disease, the course of EBVMCU is indolent, and regression is expected when immunosuppression is reduced. We present a case of EBVMCU in the gingiva of a 59-year-old male patient with long-standing pemphigus vulgaris. The initial presentation was suspicious for oral cavity cancer, which was ruled out by biopsy. After reduction of immunosuppression, the ulceration regressed and an area of exposed necrotic bone remained. Complete healing was achieved after sequestrectomy and primary closure with a local gingival flap.


Assuntos
Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Infecções por Vírus Epstein-Barr/complicações , Gengiva , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera
12.
Int J Oral Maxillofac Surg ; 49(8): 1016-1019, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31892445

RESUMO

Segmental mandibular defects require reconstruction. The fibula flap serves as a versatile flap in restoring mandibular contour and bony height. With the advances in computer-aided design and additive manufacturing technology, an innovative "one-piece" patient-specific reconstruction plate to facilitate double-barrel fibula flap shaping and bone securing was developed; the plate is described in this study. The "one-piece" plate is fabricated with individualized specifications and is mainly composed of three components: the long-bar reconstruction plate, a short-bar plate, and connecting bars. Our initial experiences showed that mandibular reconstructive surgery was greatly facilitated by the "one-piece" reconstruction plate for double-barrel fibula flap reconstruction and achieved satisfactory outcomes. A well-designed clinical trial is required to confirm the superiority of the "one-piece" reconstruction plate in the future. ClinicalTrials.gov registration: NCT03057223.


Assuntos
Retalhos de Tecido Biológico , Reconstrução Mandibular , Procedimentos de Cirurgia Plástica , Cirurgia Assistida por Computador , Transplante Ósseo , Desenho Assistido por Computador , Fíbula , Humanos , Mandíbula/cirurgia
13.
Int J Oral Maxillofac Surg ; 49(1): 13-21, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31230767

RESUMO

Three-dimensionally (3D) printed patient-specific surgical plates have been proposed to facilitate mandibular reconstruction and are attracting extensive attention. We have recently reported the high accuracy of 3D-printed patient-specific surgical plates used in head and neck reconstruction. Based on this previous work, the current study proposes a novel 'surgeon-dominated' approach to the design of 3D-printed patient-specific surgical plates. The aim of this proof-of-concept study was to explore the workflow and technical procedures of the surgeon-dominated approach. The workflow includes virtual surgery, the design and printing of patient-specific surgical devices, and real surgery. The prototype of the patient-specific surgical plate was designed by surgeons and further optimized for 3D printing by engineers. Different types of mandibular defect were tested to confirm the wide applicability of this approach. Cases in which this approach was used were reviewed and the duration of time spent on each case studied. Based on a total of 16 patients, the time spent on virtual surgery and plate design was 18.83±13.19hours, and the time taken for 3D printing, post-processing, and product delivery was 162.9±55.15hours. Therefore, this novel surgeon-dominated approach is feasible and time-saving, which would likely promote the wide application of patient-specific surgical plates and lead to a new era of 'digitization and precision' in mandibular reconstruction. ClinicalTrials.gov registration: NCT03057223.


Assuntos
Reconstrução Mandibular , Procedimentos de Cirurgia Plástica , Cirurgiões , Cirurgia Assistida por Computador , Placas Ósseas , Desenho Assistido por Computador , Humanos , Mandíbula , Impressão Tridimensional
14.
Int J Oral Maxillofac Surg ; 49(7): 862-866, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31852586

RESUMO

The facial artery pedicle nasolabial island flap (FAPNIF) is widely used for oral and maxillofacial reconstruction. However, its use in reconstruction after malignant tumour resection is limited by the possibility of ipsilateral cervical lymph node metastasis along the facial artery. Through fine dissection, it was found that the contralateral FAPNIF can be used to repair the defect after buccal carcinoma resection. The aim of this study was to evaluate the clinical outcomes of the contralateral FAPNIF for buccal defect repair. From 2013 to 2016, 30 patients underwent the repair of a buccal defect with a contralateral FAPNIF after tumour resection. Clinical outcomes and complications were recorded and quality of life was evaluated preoperatively and at 3, 6, and 12 months postoperative. The flaps survived in all 30 cases. Mean mouth opening was 2.50±0.14cm at 1 month, 3.22±0.25cm at 6 months, and 3.35±0.23cm at 12 months postoperative. With regard to patient quality of life, adverse effects included impaired aesthetics, pain, and difficulty eating; these usually subsided within 1year after surgery. The contralateral FAPNIF is easily harvested and is a safe and effective option for the repair of medium-sized buccal defects after the resection of carcinoma.


Assuntos
Neoplasias Bucais/cirurgia , Procedimentos de Cirurgia Plástica , Artérias , Estética Dentária , Humanos , Qualidade de Vida , Retalhos Cirúrgicos
15.
Int J Oral Maxillofac Surg ; 48(10): 1300-1306, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31084977

RESUMO

Ameloblastoma is a benign odontogenic tumour showing locally aggressive characteristics. This retrospective study was performed to investigate the long-term treatment outcomes of ameloblastoma and to evaluate the risk factors for recurrence. The study was conducted in the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, the University of Hong Kong and covered the years 1990-2017. Patient demographic data, radiographic pattern and findings, clinical findings, tumour site and size, World Health Organization classification, treatment modality, histological pattern, duration of follow-up, and timing of recurrence were recorded and analyzed. The potential risk factors were analyzed by Kaplan-Meier and Cox regression tests. The cases of a total of 128 patients were reviewed; 65 were male and 63 were female. The mean follow-up period was 117 months. The 5-, 10-, and 15-year recurrence rates were 9.3%, 17.6%, and 24.4%, respectively. Kaplan-Meier and Cox regression tests showed that recurrence was significantly associated with radiographic pattern, tumour size, and treatment modality. Multiple regression analysis for these three variables demonstrated that treatment modality was the only independent prognostic factor for recurrence. This study showed that radical resection is the only significant factor for a low recurrence rate of ameloblastoma and patients require long-term follow-up for late-onset recurrence.


Assuntos
Ameloblastoma , Feminino , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia , Estudos Retrospectivos , Fatores de Risco
16.
J Dent Res ; 98(3): 304-312, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30513244

RESUMO

Magnesium (Mg) has been known to play vital roles in regulating growth and various metabolic processes. In recent years, the association between Mg and tumorigenesis has raised more and more attention. However, the effects of Mg on the progression of head and neck carcinoma (HNC), as well as the mechanism behind it, remain undefined. In this study, the roles of Mg in tumorigenic activities were tested in CAL27 and FaDu cells as well as in a xenograft tumor model in nude mice. We demonstrated that a moderate increase in extracellular Mg contributed to the proliferation, migration, and invasion of 2 HNC cell lines, while the addition of Mg in drinking water promoted the growth of xenograft tumors in mice without altering their serum Mg levels. Moreover, TRPM7, a major Mg transporter, was shown to be essential for the tumorigenic activities of HNC and the Mg-induced promotive effects on HNC cells and was further shown to be associated with the activation of AKT/mTOR (mammalian target of rapamycin) signaling. In a preliminary clinical study, we determined the Mg ion concentrations in the stimulated saliva from 72 patients with nasopharynx carcinoma and 12 healthy individuals. Our data revealed that the salivary Mg levels of subjects with nasopharynx carcinoma were significantly higher than those of the healthy controls. This is correlated with our finding showing TRPM7 to be overexpressed in tumor tissues harvested from 9 patients with HNC. Therefore, we can conclude that salivary Mg level, within a certain range, could act as a risk factor for the progression of HNC, which involves the activation of AKT/mTOR signaling pathways through the TRPM7 channel. The control of salivary Mg level and the intervention of TRPM7 should not be ignored during the study of HNC.


Assuntos
Carcinoma , Neoplasias de Cabeça e Pescoço , Magnésio/metabolismo , Canais de Cátion TRPM/metabolismo , Animais , Proliferação de Células , Humanos , Camundongos , Camundongos Nus , Proteínas Serina-Treonina Quinases , Proto-Oncogene Mas , Transdução de Sinais
17.
Int J Oral Maxillofac Surg ; 47(5): 585-594, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29395670

RESUMO

Venous compromise is still the most common cause of free flap failure. The use of two venous anastomoses has been advocated to reduce venous compromise. However, the effectiveness of this approach remains controversial. A systematic review and cumulative meta-analysis was performed to assess the effect of one versus two venous anastomoses on venous compromise and free flap failure in head and neck microsurgical reconstruction. A total of 27 articles reporting 7389 flaps were included in this study. On comparison of one versus two venous anastomoses, the odds ratio (OR) for flap failure was 1.66 (95% confidence interval 1.11-2.50; P=0.014) and for venous compromise was 1.50 (95% confidence interval 1.10-2.05; P=0.011), suggesting a significant increase in the flap failure rate and venous compromise rate in the single venous anastomosis group. These results show that the execution of two venous anastomoses has significant effects on reducing the vascular compromise and free flap failure rate in head and neck reconstruction.


Assuntos
Anastomose Cirúrgica/métodos , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/cirurgia , Microcirurgia/métodos , Procedimentos de Cirurgia Plástica/métodos , Sobrevivência de Enxerto , Humanos , Complicações Pós-Operatórias/prevenção & controle
18.
Int J Oral Maxillofac Surg ; 47(5): 595-602, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29366529

RESUMO

The medial upper arm has previously been proposed as a potential free flap donor site, but the clinical application of such flaps in head and neck reconstruction has not been popular. The preliminary results of the clinical application of medial upper arm free flaps in oral cavity reconstruction are reported here. Five patients with oral cancer underwent surgical resection and neck dissection, with simultaneous reconstruction using a medial upper arm free flap. Functional outcomes were investigated using the University of Washington Quality of Life Questionnaire. Sensory-motor functions of the upper arm donor site were recorded before and after surgery. Four flaps were successfully transferred. One flap was abandoned during surgery because of a lack of perforators, and a forearm flap was used instead. All patients survived without loco-regional recurrence or distant metastasis. Functional outcomes, especially swallowing and speech, were satisfactory. The donor site scar was well hidden, with no functional impairment. This initial experience shows that the medial upper arm free flap represents an alternative perforator flap for oral cavity microsurgical reconstruction. The well-hidden scar and better texture match compared with other flaps make it suitable for oral cavity reconstruction.


Assuntos
Braço/irrigação sanguínea , Carcinoma Adenoide Cístico/cirurgia , Carcinoma de Células Escamosas/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias Bucais/cirurgia , Procedimentos Cirúrgicos Bucais/métodos , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento
19.
Oral Dis ; 21(4): 470-7, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25482163

RESUMO

OBJECTIVES: Adenoid cystic carcinoma (ACC) is one of the most common salivary gland cancers. The prognosis of adenoid cystic carcinoma is poor for its high frequency of distant metastases and insensitivity to chemotherapy or molecular therapies. This study investigated the effect of Obatoclax on adenoid cystic carcinoma cells and its cytotoxic mechanism. METHODS: Western blot, transmission electron microscopy, and pEGFP-LC3 plasmids transfection were carried out to detect autophagy in ACC cells treated with Obatoclax. 3-MA and RNA interference against Beclin 1 and ATG5 were used to inhibit autophagy. Then we used Western blot and Hochest 33342 staining for apoptosis assessment. Finally, cell viability was assessed by MTT assay. RESULTS: We found that Obatoclax induced cytoprotective autophagy which depended on ATG5 and partly on Beclin 1 in adenoid cystic carcinoma cells. Furthermore, pharmacologically inhibiting Obatoclax-induced autophagy promoted apoptosis. Downregulation of Beclin 1 or ATG5 attenuated the cytotoxicity of Obatoclax by suppressing both autophagy and apoptosis. Finally, when apoptosis was pharmacologically inhibited, autophagic cell death was initiated in adenoid cystic carcinoma cells treated with Obatoclax. CONCLUSION: In summary, Beclin 1 and ATG5 play important roles in regulating both Obatoclax-induced autophagy and apoptosis in adenoid cystic carcinoma.


Assuntos
Proteína 5 Relacionada à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Carcinoma Adenoide Cístico/tratamento farmacológico , Pirróis/farmacologia , Neoplasias das Glândulas Salivares/tratamento farmacológico , Autofagia/genética , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proteína 5 Relacionada à Autofagia/genética , Proteína Beclina-1/antagonistas & inibidores , Proteína Beclina-1/genética , Carcinoma Adenoide Cístico/genética , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Indóis , Prognóstico , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia
20.
Horm Metab Res ; 46(10): 722-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25028793

RESUMO

Lipoapoptosis is the main form of pancreatic ß-cell death in diabetes. Adiponectin is an adipocyte-derived hormone, which has anti-apoptosis effect in numerous cells. The present study was designed to explore the role of the 'extrinsic' (death receptor-induced) and the 'intrinsic' (mitochondrial) pathways in pancreatic ß-cell lipoapoptosis and the anti-apoptosis effect of adiponectin on pancreatic ß-cells. Palmitate (0.4 mmol/l) or oleate (0.4 mmol/l) was used to induce the apoptosis of Min 6 cells for 24 h. Z-LETD-FMK or Z-IEHD-FMK (40 µM) was used to inhibit the activity of caspase-8 or -9. When adiponectin was used, Min 6 cultures were pretreated in the absence or presence of fAd (5 µg/ml) for 2 h and then subjected to palmitate for 24 h. Apoptosis was evaluated using Annexin V-Cy3 kit. The expression levels of cleaved caspase-3, -8, -9, B-cell lymphoma 2 (BCL-2), and Bax were examined by Western blotting. Palmitate-induced pancreatic ß-cell apoptosis was accompanied by the activation of caspase-8, -9, and -3. Blockade of caspase-9 rather than caspase-8, showed an inhibitory effect on caspase-3 activation. Moreover, adiponectin treatment prevented palmitate-induced apoptosis by inhibition of caspase-9 activation, but not of caspase-8, and induced an upregulation of BCL-2 and a downregulation of Bax in protein level. Both extrinsic and intrinsic pathways are activated in pancreatic ß-cell lipoapoptosis, and the intrinsic apoptosis pathway is the major one. Adiponectin prevents pancreatic ß-cells from apoptosis by inhibition of intrinsic apoptosis pathway via regulation of the BCL2 family. Therefore, protection of intrinsic apoptosis pathway is a potential therapeutic strategy for diabetes.


Assuntos
Adiponectina/metabolismo , Apoptose , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Adiponectina/genética , Animais , Caspase 3/genética , Caspase 3/metabolismo , Caspase 8/genética , Caspase 8/metabolismo , Caspase 9/genética , Caspase 9/metabolismo , Linhagem Celular , Camundongos , Mitocôndrias/enzimologia , Mitocôndrias/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transdução de Sinais , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
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