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1.
Eur Arch Otorhinolaryngol ; 279(12): 5735-5740, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35680654

RESUMO

OBJECTIVE: To evaluate the feasibility and efficacy in selected T4a glottic cancer (thyroid cartilage invasion adherence to the anterior commissure) treated with frontolateral vertical partial laryngectomy (FLVPL) and laryngeal framework reconstruction using titanium mesh. METHODS: Six patients with the limited T4a glottic cancer with thyroid cartilage destruction adherence to the anterior commissure, underwent FLVPL from 2009 to 2016 in Sun Yat-Sen University Cancer Center. All patients were followed up postoperatively. RESULTS: All patients comprised radical tumor resection and favorable functional outcomes, and no aspiration and laryngeal stenosis were observed. According to postoperative pathology, four patients should go through postsurgical radiotherapy with a mean dose of 66 Gy. But one of them refused to undergo postoperative radiotherapy, who observed local recurrence in postcricoid area underwent total laryngectomy (TL) and ipsilateral selected neck dissection in post-surgery two year. During follow-up period, all patients were still alive, and five patients without local recurrence and distant metastases. CONCLUSION: FLVPL and laryngeal framework reconstruction using titanium mesh is one viable surgical procedure to obtain adequate oncologic and functional outcomes.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Laríngeas , Neoplasias da Língua , Humanos , Laringectomia/métodos , Neoplasias Laríngeas/patologia , Cartilagem Tireóidea/cirurgia , Cartilagem Tireóidea/patologia , Glote/cirurgia , Glote/patologia , Titânio , Carcinoma de Células Escamosas/patologia , Neoplasias da Língua/patologia , Estudos Retrospectivos
2.
Eur Arch Otorhinolaryngol ; 273(3): 555-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25480477

RESUMO

To explore the feasibility of endoscopic thyroidectomy via breast areola and axilla approach. The clinical data of 36 cases that underwent endoscopic thyroidectomy via breast areola and axilla approach from February 2012 to December 2013 were reviewed. All cases were completed, the mean operation time was 136.3 min (95-183 min), intraoperative blood loss was 15.8 ml (5-60 ml). The average hospitalization time was 5 days (4-6 days). There were no conversions to open surgery, no permanent nerve injuries, and no cases of hypoparathyroidism. Three patients had postoperative subcutaneous ecchymosis who were cured spontaneously after 1 month. Endoscopic thyroidectomy is safe and feasible for patients with thyroid diseases with good cosmetic results, and is worthy of being widely applied for patients who have cosmetic demand.


Assuntos
Axila , Endoscopia/métodos , Mamilos , Tireoidectomia/métodos , Adolescente , Adulto , Perda Sanguínea Cirúrgica , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Duração da Cirurgia , Doenças da Glândula Tireoide/cirurgia , Adulto Jovem
3.
J Transl Med ; 11: 59, 2013 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-23497344

RESUMO

BACKGROUND: Protein tyrosine kinase 6 (PTK6), also known as breast tumor kinase (Brk), was a nonreceptor tyrosine kinase containing SH3, SH2, and tyrosine kinase catalytic domains. The deregulated expression of PTK6 was observed in various human cancers. However, little was known about PTK6 expression and its clinicopathological significance in human laryngeal squamous cell carcinoma (LSCC). MATERIALS: PTK6 expression was evaluated in 7 pairs of surgically resectable laryngeal tissues by Western blotting and in 13 pairs of surgically resectable laryngeal tissues by reverse transcription-PCR (RT-PCR). Using immunohistochemistry, we performed a retrospective study of the PTK6 expression levels on 134 archival LSCC paraffin-embedded samples. Prognostic outcomes correlated with PTK6 were examined using Kaplan-Meier analysis and Cox proportional hazards model. RESULTS: The PTK6 expression level was lower in LSCC tissues than in the adjacent noncancerous epithelial laryngeal tissues by Western blots and RT-PCR. By immunohistochemical analysis, we observed high expression of PTK6 in 25 of 76 (32.9%) adjacent noncancerous epithelial laryngeal tissues and in 39 of 134 (29.1%) of LSCC, respectively. Multivariate analysis demonstrated that pN status and the expression level of PTK6 (P < 0.05) were independent and significant prognostic factors. In the primary LSCC category, median DFS (disease free survival) of high, medium and low PTK6 expression patients were 88.5 months ,74.5 months and 49.0 months (log-rank test, P = 0.002); median OS (overall survival) of high, medium and low PTK6 expression patients were 88.5 months ,76.3 months and 65.7 months (log-rank test, P = 0.002). Reduced cytoplasmic PTK6 expression in LSCC was significantly associated with late pN status (P =0.005, r = 0.27), advanced pTNM stages (III and IV) (P =0.027, r = 0.147), and poor differentiated LSCC (P <0.0001, r = 0.486). In adjacent paracancerous laryngeal epithelial samples, median DFS of high, medium and low PTK6 expression patients were 92.6 months ,75.6 months and 48.5 months (log-rank test, P = 0.020); median OS of high, medium and low PTK6 expression patients were 92.9 months ,78.9 months and 74.6 months (log-rank test, P = 0.042). CONCLUSION: The present findings indicated that cytoplasmic PTK6 expression is a potential prognostic factor for survival in LSCC patients. High expression of PTK6 was associated with favorable OS and DFS in LSCC patients.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Laríngeas/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Tirosina Quinases/metabolismo , Idoso , Sequência de Bases , Western Blotting , Primers do DNA , Feminino , Humanos , Imuno-Histoquímica , Masculino , Prognóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa
4.
J Org Chem ; 78(1): 35-41, 2013 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-22946828

RESUMO

An efficient synthesis of the Stemona alkaloid (-)-sessilifoliamide J (1) in 12 steps and 7.7% overall yield from the known building block 8 is presented. The synthesis features the Corey lactonization reaction and a highly diastereoselective α-methylation reaction to build the spiro-lactone moiety.


Assuntos
Alcaloides/síntese química , Lactonas/síntese química , Compostos de Espiro/síntese química , Alcaloides/química , Lactonas/química , Estrutura Molecular , Compostos de Espiro/química , Stemonaceae/química , Estereoisomerismo
5.
J Oral Maxillofac Surg ; 71(5): 960-4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23298806

RESUMO

PURPOSE: The purpose of this study was to assess the clinical application and therapeutic efficacy of through-and-through cheek defects reconstructed with folded anterolateral thigh (ALT) flaps. PATIENTS AND METHODS: From January 2009 to May 2012, 10 patients with through-and-through cheek defects resulting from resection of cheek tumor underwent reconstruction with the folded ALT flap at Sun Yat-Sen University Cancer Center, Guangzhou, China. Surgical procedures in harvesting the ALT flap, as well as the surgical anatomy, are described, and the success rate is reported. RESULTS: All ALT flaps were fasciocutaneous flaps. One patient with a thrombotic event required operative exploration in the perioperative period. All 10 flaps were based on a single perforator for reconstruction of defects. In all 10 cases, the donor site was closed primarily for the ALT flap, leaving only a linear scar that was inconspicuous with normal clothing, and the thigh had no functional deficit. CONCLUSIONS: The free ALT flap has good pliability and can be folded for the reconstruction of both the inner and outer lining of through-and-through cheek defects. This flap presents good functional results at the recipient site with the additional advantages of minimal donor-site morbidity, a very acceptable esthetic result, and a high level of patient satisfaction.


Assuntos
Bochecha/cirurgia , Fáscia/transplante , Retalhos de Tecido Biológico/transplante , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Adulto , Idoso , Anastomose Cirúrgica/métodos , Estética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/cirurgia , Estadiamento de Neoplasias , Satisfação do Paciente , Retalho Perfurante/patologia , Estudos Retrospectivos , Gordura Subcutânea/cirurgia , Coxa da Perna/cirurgia , Coleta de Tecidos e Órgãos/métodos , Sítio Doador de Transplante/patologia , Resultado do Tratamento
6.
Org Biomol Chem ; 10(6): 1275-84, 2012 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-22183493

RESUMO

The one-pot reductive coupling of N-acylcarbamates with activated alkenes is described. The method is based on partial reduction of N-acylcarbamates with DIBAL-H, followed by N-acyliminium ion formation and SmI(2)-mediated radical coupling with activated alkenes. Both acyclic and cyclic N-acylcarbamates can be used as stable substrates, and a range of activated alkenes serve as effective radical receptors. The reductive coupling of l-N-acylcarbamates 12/13 gave 2,5-disubstituted pyrrolidine derivatives in high trans-diastereoselectivities. The reductive coupling with penta-2,4-dienoate proceeded exclusively in a 1,6-addition fashion, producing a single non-conjugated E-isomer. On the basis of this method, a three-step construction of pyrrolo[1,2-a]azepin-5-one 16, the skeleton of many stemona alkaloids and lehmizidine alkaloids, and a seven-step synthesis of (-)-xenovenine (pyrrolizidine cis-223H, ent-6), the unnatural enantiomer of the frog/ant venom alkaloid possessing potent inhibitory activity towards nAChR channel, were achieved starting from L-12.


Assuntos
Alcenos/química , Azepinas/síntese química , Carbamatos/química , Pirróis/síntese química , Alcaloides de Pirrolizidina/síntese química , Azepinas/química , Estrutura Molecular , Oxirredução , Pirróis/química , Alcaloides de Pirrolizidina/química , Estereoisomerismo
7.
Eur Arch Otorhinolaryngol ; 269(7): 1845-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22116384

RESUMO

The free jejunum flap approach is the optimal option for circumferential pharyngolaryngectomy reconstruction. In this study, we designed a "watch window" for monitoring buried free jejunum flaps, thereby allowing us to assess graft viability. From 2007 to 2011, 14 patients with hypopharyngeal cancer underwent circumferential pharyngolaryngectomy that was reconstructed using a free jejunum flap at the Sun Yat-sen University Cancer Centre. During the closing of the neck incision, a "watch window" was designed for postoperative monitoring. Two patients experienced thrombosis of the pedicle. One was detected early and successfully rescued by removal of the thrombosis, the other one managed with a second free jejunum flap. The success rate of the buried flaps was 92.9%. No pharyngocutaneous fistulas or strictures occurred. All patients eventually resumed oral feeding and swallowing. The "watch window" technique for monitoring buried free jejunum flaps is simple, reliable and useful for finding vascular problems. Level of evidence Case series.


Assuntos
Neoplasias Hipofaríngeas/cirurgia , Jejuno/transplante , Monitorização Fisiológica/métodos , Esvaziamento Cervical , Complicações Pós-Operatórias/cirurgia , Trombose , Técnicas de Fechamento de Ferimentos , Intervenção Médica Precoce/métodos , Feminino , Sobrevivência de Enxerto , Humanos , Neoplasias Hipofaríngeas/patologia , Hipofaringe/patologia , Hipofaringe/cirurgia , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical/efeitos adversos , Esvaziamento Cervical/métodos , Avaliação de Resultados em Cuidados de Saúde , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Fluxo Sanguíneo Regional , Reoperação/métodos , Reprodutibilidade dos Testes , Retalhos Cirúrgicos/efeitos adversos , Retalhos Cirúrgicos/irrigação sanguínea , Trombose/etiologia , Trombose/cirurgia
8.
Artigo em Inglês | MEDLINE | ID: mdl-22327028

RESUMO

OBJECTIVE: To investigate the clinical therapeutic outcomes and neck node control of a pretreatment neck dissection in the chemoradiation protocol of organ preservation for N2-N3 of supraglottic and hypopharyngeal carcinoma. METHODS: Forty-six patients (group A) with untreated N2 or N3 squamous cell carcinoma of the supraglottis or hypopharynx underwent pretreatment neck dissection in a chemoradiation protocol, while 39 patients (group B) did not undergo pretreatment neck dissection in a chemoradiation protocol. Salvage surgeries were used for local or cervical node residual tumor or recurrence after chemoradiotherapy. RESULTS: In group A, the mean time between neck dissection and chemoradiation was 21 days (range 15-29). Only 3 patients (6.5%) experienced wound complications. A 'boost' of radiation of 12 Gy was delivered after 33 neck dissections (64.8%) in patients with extracapsular spread. The Kaplan-Meier 5-year overall survival rate was 42.5%. The 5-year overall survival rate and disease-specific survival rate in group A was 42.5 and 46.4%. The rate of neck node control in group A was better than that in group B (86.3 vs. 65.9%, p = 0.02). CONCLUSIONS: Pretreatment neck dissection in a chemoradiation protocol for supraglottic or hypopharyngeal carcinoma showed low complication rates, no delay for radiation, optimal radiation doses, and a high nodal disease control.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Hipofaríngeas/terapia , Esvaziamento Cervical/métodos , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Quimiorradioterapia/mortalidade , Feminino , Seguimentos , Glote/cirurgia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/patologia , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Pescoço/cirurgia , Esvaziamento Cervical/mortalidade , Recidiva Local de Neoplasia/mortalidade , Complicações Pós-Operatórias/mortalidade , Terapia de Salvação/métodos , Terapia de Salvação/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço
9.
J Org Chem ; 76(12): 4952-63, 2011 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-21574569

RESUMO

The SmI(2)-mediated radical coupling reactions of ß-hydroxylated pyrrolidine/piperidine aza-hemiacetals 8 and 9 and N,S-acetals 6 and 33 with α,ß-unsaturated compounds are described. This method allows a rapid access to ß-hydroxylated pyrrolidines, piperidines, pyrrolizidinones, and indolizidinones. Starting from N,S-acetal 33 and via a common intermediate 27, the alkaloids hyacinthacine A(2) (2), uniflorine A (3, 6-epi-casuarine), and the unnatural epimer 7-epi-casuarine (37) have been synthesized in four and five steps with overall yields of 34%, 16%, and 13%, respectively. The radical mechanism of the coupling reactions has been confirmed by controlled experiments, which also allowed deducing the anionic mechanism in the coupling between N,S-acetal 6 and carbonyl compounds. This demonstrates that the mechanisms of these SmI(2)-mediated reactions are switchable from Barbier-type anionic to radical by cooperative action of BF(3)·OEt(2) and t-BuOH.


Assuntos
Acetais/química , Alcaloides/síntese química , Compostos Aza/química , Indolizinas/síntese química , Iodetos/química , Pirróis/síntese química , Alcaloides de Pirrolizidina/síntese química , Samário/química , Radicais Livres/química , Hidroxilação , Estrutura Molecular , Estereoisomerismo
10.
Eur Arch Otorhinolaryngol ; 268(12): 1809-12, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21387188

RESUMO

This study compared the reliability, practicability and impact to donor site functionality of radial forearm (RF) and anterolateral thigh (ALT) flaps used for the reconstruction of head and neck soft-tissue defects. The clinical data of patients who underwent reconstruction using RF flaps (n = 53) and ALT flaps (n = 21) after tumour ablation were reviewed. Pedicle length, skin area harvested and flap survival rate were compared between the two flap types. A questionnaire was used to compare the patients' perceptions of donor site functionality. Pedicle length did not significantly differ between RF and ALT flaps (7.5 vs. 9 cm, p = 0.733). A significantly larger mean area of skin was harvested in the ALT group than in the RF group (65 vs. 38 cm(2), p = 0.001). Flap survival rates did not differ between the two groups (p = 0.554). Patients in the ALT group were more satisfied with the appearance of the donor sites than were those in the RF group (p = 0.029). Significantly more patients in the RF group complained of donor site numbness than in the ALT group (p = 0.014). No ALT group patients complained of movement impairment or weakness at the donor sites, but 10% of RF group patients experienced impairment (p = 0.014) and 35% felt weakness (p = 0.001). The ALT and RF flaps showed similar practicability and reliability for the reconstruction of soft-tissue defects, but ALT flaps had fewer impacts to donor site functionality than RF flaps.


Assuntos
Antebraço/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Transplante de Pele/métodos , Retalhos Cirúrgicos , Coxa da Perna/cirurgia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
11.
Head Neck ; 43(1): 98-107, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32985734

RESUMO

BACKGROUND: Surgical access for retropharyngeal lymph node (RPLN) dissection is difficult. We aimed to examine the efficacy of transcervical endoscopic RPLN dissection (TSE-RPLND) for recurrent RPLN in nasopharyngeal carcinoma (NPC). METHODS: From April 2013 to February 2019, a total of 31 patients with NPC diagnosed with RPLN recurrence underwent TSE-RPLND. The clinical characteristics, complications, and survival outcomes were retrospectively analyzed. RESULTS: The mean duration of surgery, quantity of bleeding and postoperative hospitalization stay were 347.9 minutes, 107.7 mL, and 8.7 days, respectively. After a median follow-up of 31.0 months, the 2-year locoregional relapse-free survival, distant metastasis-free survival, progression-free survival, and overall survival rates were 63.9%, 95.2%, 59.9%, and 83.3%, respectively. The long-term incidences of swallowing problems, permanent nutrient tube, tongue atrophy, and shoulder problems were 6 (19.4%), 3 (9.7%), 3 (9.7%), and 3 (9.7%), respectively. CONCLUSIONS: TSE-RPLND is an effective method to treat RPLN recurrence in NPC, but nerve injury-related complications should not be ignored.


Assuntos
Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Dissecação , Humanos , Excisão de Linfonodo , Linfonodos/cirurgia , Metástase Linfática , Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/cirurgia , Estudos Retrospectivos
12.
Parkinsons Dis ; 2020: 6378673, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005317

RESUMO

OBJECTIVE: The present study investigated the clinical features and correlates of poor nighttime sleepiness (PNS) in patients with Parkinson's disease (PD). METHODS: One hundred ten patients with PD (divided into PD-PNS group and PD-nPNS group) and forty-seven controls (nPD-PNS group) were enrolled in this study. Demographic information was collected. Patients were assessed according to the unified Parkinson's disease rating scale (UPDRS) and Hoehn-Yahr (H&Y) stage scale. Patients were also evaluated according to the Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), rapid eye movement sleep behavior disorder screening questionnaire (RBD-SQ), restless leg syndrome (RLS) diagnosis, Hamilton's depression scale (HAMD), and Hamilton's anxiety scale (HAMA). RESULTS: The prevalence of PNS was 55.45% (61/110) in patients with PD. The PD-PNS group tended to have a longer duration of disease, higher UPDRS-I and UPDRS-III scores, a higher percentage of RLS patients, and higher HAMA and HAMD scores than those of the PD-nPNS group. The PD-PNS group tended to have a higher percentage of RBD and RLS patients and higher HAMA and HAMD scores than those of the nPD-PNS group. Analysis of the PSQI components and PSQI impact factors showed that the PD-PNS group had worse subjective sleep quality (χ 2 = -2.267, P = 0.023), shorter sleep latency (χ 2 = -2.262, P = 0.024), fewer sleep medications (χ 2 = -4.170, P ≤ 0.001), worse daytime functioning (χ 2 = -2.347, P = 0.019), and an even higher prevalence of increased nocturia (χ 2 = 4.447, P = 0.035), nightmares (χ 2 = 7.887, P = 0.005), and pain (χ 2 = 9.604, P = 0.002) than those of the nPD-PNS group. Analysis also indicated that the PSQI global score positively correlated with BMI (r = 0.216, P < 0.05), H&Y stage (r = 0.223, P < 0.05), UPDRS-I (r = 0.501, P < 0.01), UPDRS-III (r = 0.425, P < 0.01), ESS (r = -0.296, P < 0.01), RBD (r = 0.227, P < 0.05), RLS (r = 0.254, P < 0.01), HAMA (r = 0.329, P < 0.01), and HAMD (r = 0.466, P < 0.01). In the final model, H&Y stage, RLS, UPDRS-III, and HAMD remained associated with the PQSI score (P ≤ 0.001, P ≤ 0.001, P = 0.049, P ≤ 0.001, respectively). CONCLUSIONS: Our data showed that PNS was common in patients with PD. H&Y stage, UPDRS-III, HAMD, and RLS were positively associated with PNS. Attention to the management of motor symptoms, RLS, and depression may be beneficial to nighttime sleep quality in patients with PD.

13.
Medicine (Baltimore) ; 98(49): e18245, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804352

RESUMO

BACKGROUND: Optimal glycemic control is required to restrain the increase of cardiovascular events in patients with type 2 diabetes. The effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular events and mortality in those patients are not well established. This meta-analysis was conducted to assess the effects of SGLT2 inhibitors on cardiovascular events and mortality in patients with type 2 diabetes. METHODS: We conducted a systematic literature search of Medline, Embase and Cochrane Library and included randomized controlled trials (RCTs) of 3 different SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin) that evaluated the effects on cardiovascular outcomes and mortality in the final meta-analysis. The intervention arm was defined either as SGLT2 inhibitor monotherapy or as SGLT2 inhibitor add-on to other non-SGLT2 inhibitor antidiabetic agents (ADAs). RESULTS: Forty-two trials with a total of 61,076 patients with type 2 diabetes were included in the meta-analysis. Compared with the control, SGLT2 inhibitor treatment was associated with a reduction in the incidence of major adverse cardiovascular events (MACEs) (OR = 0.86, 95% CI 0.80-0.93, P < .0001), myocardial infarction (OR = 0.86, 95% CI 0.79-0.94, P = .001), cardiovascular mortality (OR = 0.74, 95% CI 0.67-0.81, P < .0001) and all cause mortality (OR = 0.85, 95% CI 0.79-0.92, P < .0001). However, the risk of ischemic stroke was not reduced after SGLT2 inhibitor treatment in patients with type 2 diabetes (OR = 0.95, 95% CI 0.85-1.07, P = .42). CONCLUSION: These data suggest a decreased risk of harm with SGLT2 inhibitor as a class with respect to cardiovascular events and mortality.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Humanos
14.
Cell Prolif ; 52(2): e12536, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30341788

RESUMO

OBJECTIVES: The present study aimed to reveal expression status of the neddylation enzymes in HNSCC and to elucidate the anticancer efficacy and the underlying mechanisms of inhibiting neddylation pathway. MATERIALS AND METHODS: The expression levels of neddylation enzymes were estimated by Western blotting in human HNSCC specimens and bioinformatics analysis of the cancer genome atlas (TCGA) database. Cell apoptosis was evaluated by Annexin V fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) stain and fluorescence-activated cell sorting (FACS). Small interfering RNA (siRNA) and the CRISPR-Cas9 system were used to elucidate the underlying molecular mechanism of MLN4924-induced HNSCC apoptosis. RESULTS: Expression levels of NAE1 and UBC12 were prominently higher in HNSCC tissues than that in normal tissues. Inactivation of the neddylation pathway significantly inhibited malignant phenotypes of HNSCC cells. Mechanistic studies revealed that MLN4924 induced the accumulation of CRL ligase substrate c-Myc that transcriptionally activated pro-apoptotic protein Noxa, which triggered apoptosis in HNSCC. CONCLUSIONS: These findings determined the over-expression levels of neddylation enzymes in HNSCC and revealed novel mechanisms underlying neddylation inhibition induced growth suppression in HNSCC cells, which provided preclinical evidence for further clinical evaluation of neddylation inhibitors (eg, MLN4924) for the treatment of HNSCC.


Assuntos
Apoptose/efeitos dos fármacos , Ciclopentanos/farmacologia , Inibidores Enzimáticos/farmacologia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteína NEDD8/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Pirimidinas/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Proteína NEDD8/agonistas , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
15.
Laryngoscope ; 129(2): 387-395, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30325027

RESUMO

OBJECTIVE: To compare survival effects of comprehensive neck dissection (CND) and selective neck dissection (SND) for patients with nasopharyngeal carcinoma (NPC) with only regional failure. METHODS: A total of 294 recurrent T0N1-3M0 NPC patients who underwent neck dissection in Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China, between January 1984 and February 2014, were enrolled in the survival and interaction analyses. Using propensity scores to adjust for potential prognostic factors, an additional well-balanced cohort of 210 patients was constructed by matching each patient who received SND with one patient who underwent CND (1:1); the differences were then compared between SND and CND in terms of overall survival (OS), local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), and distant metastasis-free survival (DMFS). RESULTS: Both univariate and multivariate analyses showed that SND was not inferior to CND (P > 0.05) but demonstrated that extracapsular spread (ECS) (hazard ratio [HR] 3.49, 95% confidence interval [CI] 2.30-5.29, P < 0.001), recurrent N stage (rN stage) (HR 1.96, 95% CI 1.29-2.97, P = 0.002), and positive margins (HR 3.67, 95% CI 2.40-5.62, P < 0.001) were independent poor prognostic factors for OS. The interaction effects between the dissection style and each independent factor were not significant for OS, LRFS, RRFS, or DMFS (P > 0.05). Furthermore, no survival differences were found between SND and CND in the case-matched cohort in terms of OS, LRFS, RRFS, or DMFS (P = 0.550, 0.930, 0.214, and 0.146, respectively). CONCLUSION: With a similar radical dissection extent around the tumor rather than dissection of extensive lymph region distal to the lesion, SND is not inferior to CND for patients with NPC with only cervical failure. ECS, rN stage, and positive margins were adverse independent prognostic factors for patients with NPC. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:387-395, 2019.


Assuntos
Carcinoma Nasofaríngeo/cirurgia , Neoplasias Nasofaríngeas/cirurgia , Esvaziamento Cervical/mortalidade , Esvaziamento Cervical/métodos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Pescoço/patologia , Pescoço/cirurgia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
16.
Eur J Surg Oncol ; 45(11): 2143-2150, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31253544

RESUMO

BACKGROUND: We aimed to explore whether the anatomic extent of lymph node metastases (AE-LNM) could independently predict prognosis of node-positive major salivary gland carcinoma (MaSGC). METHODS: A total of 376 pathologically node-positive MaSGC patients were identified from the Surveillance, Epidemiology and End Results database and constituted the training cohort. Using the X-Tile program, these patients were divided into three groups based on AE-LNM degrees. Discrimination of overall survival (OS) and disease-specific survival (DSS) was evaluated and compared with the 8th American Joint Committee on Cancer (AJCC) pN classification. The results were externally validated by 220 patients in a Chinese multicenter cohort (Validation cohort). RESULTS: Using the training cohort, AE-LNM was divided into Extent 1 (spread to parotid LNs or level I), Extent 2 (spread to level II-IV) and Extent 3 (spread to level V or bilateral LNs or rare LNs). Regarding both OS and DSS, the AE-LNM model revealed clear separation of survival curves, while the pN classification failed to discriminate the prognosis of pN1 and pN2 patients. When we incorporated both the AE-LNM model and AJCC pN classification into the same multivariate Cox analyses, AE-LNM was still an independent prognostic factor, while the AJCC pN classification lost its significance. These results were externally validated by the validation cohort. CONCLUSION: AE-LNM is an independent nodal prognosticator for node-positive MaSGC and may have improved discriminative ability over the current AJCC pN classification. Integration of anatomic extent of LNM into the current AJCC N classification could be considered.


Assuntos
Adenocarcinoma/patologia , Linfonodos/patologia , Neoplasias das Glândulas Salivares/patologia , Adulto , Idoso , Carcinoma de Células Acinares/patologia , Carcinoma Adenoide Cístico/patologia , Carcinoma Ductal/patologia , Carcinoma Mucoepidermoide/patologia , China , Estudos de Coortes , Feminino , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Parotídeas/patologia , Prognóstico , Programa de SEER , Taxa de Sobrevida , Estados Unidos
18.
Cancer Manag Res ; 10: 4523-4535, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30349385

RESUMO

BACKGROUND: Global data demonstrate minimal improvement in the survival rate for oral cavity cancer (OCC) patients. We wished to know whether or not clinical features and survival rate have changed over time for OCC patients receiving initial treatment and follow-up at a large cancer center in China. METHODS: Clinical features and survival data were collected on patients diagnosed during the successive decades of 1960-1969 (n=253), 1970-1979 (n=497), 1980-1989 (n= 659), 1990-1999 (n=793), and 2000-2009 (n=1,160) at the Sun Yat-sen University Cancer Center. RESULTS: Over time, the overall 5-year survival rate for OCC patients was 52.0%. According to tumor localization, this rate was 71.4% for lip cancer, 56.3% for oral tongue cancer, and 42.7% for other parts of the oral cavity. From the 1960s to the 2000s, the 5-year survival rate steadily improved from 47.8% to 55.6% (P<0.001). Survival steadily decreased with age and was higher for women than for men in the 3 most recent decades. The survival rate for male patients was constant over time, while the rate for female patients improved dramatically. Obvious trends in clinical features over time included the following: increasing age of patients, increasing proportions of localized disease at diagnosis, decreasing proportions of diagnoses of lip cancer, decreasing proportions of diagnoses of squamous cell carcinoma, and decreasing proportions of non-surgical treatment approaches. CONCLUSION: The survival rate has steadily improved for OCC patients at this cancer center.

19.
Chin J Cancer ; 35(1): 89, 2016 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-27729091

RESUMO

BACKGROUND: The increasing incidence of radiation-induced osteosarcoma of the maxilla and mandible (RIOSM) has become a significant problem that can limit long-term survival. The purpose of this study was to analyze the association of clinicopathologic characteristics with treatment outcomes and prognostic factors of patients who developed RIOSM after undergoing radiotherapy for nasopharyngeal carcinoma (NPC). METHODS: We reviewed the medical records of 53,760 NPC patients admitted to Sun Yat-sen University Cancer Center during the period August 1964 to August 2012. Of these patients, 47 who developed RISOM and met inclusion criteria were included in this study. Two of these 47 patients refused treatment and were then excluded. RESULTS: For all patients treated for NPC at Sun Yat-sen University Cancer Center during the study period, the total incidence of RIOSM after radiotherapy was 0.084% (47/53,760). Two patients (4.4%) had metastases at the diagnosis of RIOSM. Thirty-nine of the 45 (86.7%) patients underwent surgery for RIOSM; most patients (24/39; 61.5%) who underwent resection had gross clear margins, with 15 patients (38.5%) having either a gross or microscopic positive margin. All patients died. The 1-, 2-, and 3-year overall survival (OS) rates for the entire cohort of 45 patients were 53.3%, 35.6% and 13.5%, respectively. The independent prognostic factors associated with high OS rate were tumor size and treatment type. CONCLUSIONS: RISOM after radiotherapy for NPC is aggressive and often eludes early detection and timely intervention. Surgery combined with postoperative chemotherapy might be an effective treatment to improve patient survival.


Assuntos
Neoplasias Mandibulares/etiologia , Neoplasias Maxilares/etiologia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Osteossarcoma/etiologia , Radioterapia/efeitos adversos , Neoplasias Ósseas/etiologia , Neoplasias Ósseas/patologia , Neoplasias Ósseas/cirurgia , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/cirurgia , Neoplasias Maxilares/patologia , Neoplasias Maxilares/cirurgia , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/patologia , Neoplasias Induzidas por Radiação/cirurgia , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/cirurgia , Osteossarcoma/patologia , Osteossarcoma/cirurgia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
J Clin Hypertens (Greenwich) ; 16(10): 760-5, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25113653

RESUMO

The authors aimed to investigate the relationship between serum gamma-glutamyltransferase (GGT) and prehypertension, as well as the modification of other metabolic risk factors in a large cohort of Chinese individuals. The data were collected via a community-based health examination survey in central China. Blood pressure, body mass index (BMI), and levels of GGT, fasting blood glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lipid indicators were measured. In total, data from 18,302 patients with available biomarkers were included in the present study. Elevated blood pressure was associated with increased GGT concentration (P<.001). After adjusting for age, sex, BMI, fasting blood glucose, lipid indicators, AST, and family history of hypertension, the association between GGT levels and prehypertension remained significant (P=.021). The adjusted odds ratios (95% confidence interval) for prehypertension across quintiles of GGT level were 1.00, 1.057 (1.012-1.334), 1.068 (0.916-1.254), 1.024 (0.851-1.368), and 1.272 (1.027-1.593), respectively. In stratified analyses, the association between GGT levels and prehypertension was significant in women but was not significant in men. Moreover, additive effect of BMI and age on the effect of GGT levels on prehypertension (both P for interaction <.001) was observed. In summary, GGT levels were positively associated with prehypertension in women, independent of other metabolic factors. Furthermore, BMI and age may amplify the effects of GGT levels on prehypertension. These findings suggest that monitoring the levels of GGT could help in the diagnosis and monitoring of prehypertension.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pré-Hipertensão/sangue , Pré-Hipertensão/diagnóstico , gama-Glutamiltransferase/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Glicemia/metabolismo , Índice de Massa Corporal , China , Estudos de Coortes , Feminino , Predisposição Genética para Doença/genética , Inquéritos Epidemiológicos , Humanos , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Pré-Hipertensão/genética , Distribuição Aleatória , Fatores de Risco , Adulto Jovem
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