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1.
Exp Cell Res ; 383(2): 111503, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31336100

RESUMO

Hypoxic blood-brain barrier (BBB) dysfunction is a common feature of CNS diseases however mechanisms underlying barrier disturbance are still largely unknown. This study investigated the role of transforming growth factor ß (TGFß), a cytokine known to induce expression of the proprotein convertase Furin, in hypoxia-mediated barrier compromise. We show that exposure of brain endothelial cells (ECs) to hypoxia (1% O2) rapidly stimulates their migration. Additional exogenous TGFß (0.4 nM) exposure potentiated this effect and increased Furin expression in a TGFß type I receptor activin-like kinase 5 (ALK5) - dependent manner (prevented by 10 µM SB431542). Furin inhibition prevented hypoxia-induced EC migration and blocked TGFß-induced potentiation suggesting existence of a feedback loop. TGFß and Furin were also critical for hypoxia-induced BBB dysfunction. TGFß treatment aggravated hypoxia-induced BBB permeability but ALK5 or Furin blockade reversed injury-induced permeability changes. Thus during insult Furin compromises endothelial integrity by mediating the effects of TGFß. Targeting the Furin or ALK5 pathway may offer novel therapeutic strategies for improving BBB stability and CNS function during disease.

2.
Radiat Oncol ; 13(1): 194, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30285884

RESUMO

BACKGROUND: Radiation therapy is the standard radical treatment for nasopharyngeal carcinoma (NPC) but also causes transient as well as long-term complications. Patients who develop severe radiation-induced brainstem injuries have a poor prognosis due to the lack of effective medical therapies. However, the relationship between brainstem injury and radiation volume dose is unknown. In this study, we found that radiation-induced brainstem injury was significantly associated with brainstem dose per unit volume. METHODS: A retrospective analysis was performed on a consecutive cohort of 327 patients with NPC receiving IMRT from May 2005 to December 2014. Dose-volume data and long-term outcome were analyzed. RESULTS: The median follow-up duration was 56 months (range, 3-141 months), and six with T4 and two with T3 patients had radiation-induced brainstem injuries. The 3-year and 5-year incidences were 2.2% and 2.8%, respectively. The latency period of brainstem injury ranged from 9 to 58 months, with a median period of 21 months. The Cox regression analysis showed that brainstem radiation toxicity was associated with the T4 stage, D2% of gross tumor volume of nasopharyngeal primary lesions and their direct extensions (GTVnx), Dmax (the maximum point dose), D1%, D0.1cc (the top dose delivered to a 0.1-ml volume), and D1cc (the top dose delivered to a 1-ml volume) of the brainstem (p < 0.05). Receiver operating characteristic (ROC) curves showed that GTVnx D2% and the Dmax, D1%, D0.1cc, and D1cc of the brainstem were significant predictors of brainstem injury. The area under the ROC curve for these five parameters was 0.724, 0.813, 0.818, 0.818, and 0.798, respectively (p < 0.001), and the cutoff points 77.26 Gy, 67.85 Gy, 60.13 Gy, 60.75 Gy, and 54.58 Gy, respectively, were deemed as the radiation dose limit. CONCLUSIONS: Radiotherapy-induced brainstem injury was uncommon in patients with NPC who received definitive IMRT. Multiple dose-volume data may be the dose tolerance of radiation-induced brainstem injury.


Assuntos
Tronco Encefálico/patologia , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Lesões por Radiação/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Tronco Encefálico/efeitos da radiação , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Prognóstico , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos
3.
J Cancer ; 9(9): 1642-1651, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29760803

RESUMO

Background: This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods: A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results: After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

4.
World J Surg Oncol ; 15(1): 216, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-29202837

RESUMO

BACKGROUND: The purpose of this case series is to investigate the relationship between splenic thickness (ST) and postoperative outcomes after hepatic resection in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) patients. METHODS: The clinical data of 320 patients with HBV-associated HCC who had undergone liver resection were retrospectively analyzed. The value of ST in predicting postoperative outcomes was evaluated. RESULTS: A total of 320 patients were enrolled in the study. An increase in ST was significantly associated with an increase in portal vein diameter (PVD), indocyanine green retention rate 15 min (ICG R15), and total bilirubin (TBIL); however, it was negatively correlated with platelet count (PLT). Post-hepatectomy liver failure (PHLF) occurred in 35 (10.9%) patients. Multivariate logistic regression analysis showed that ST was an independent predictor of morbidity and mortality after hepatectomy. Meanwhile, ST was associated with an almost sixfold increased risk for developing perioperative complications (OR 5.678; 95% CI 2.873 to 11.224; P < 0.001) and almost 13-fold increased risk for mortality after hepatectomy (OR 13.007; 95% CI 1.238 to 136.627; P = 0.033).The area under the receiver operating characteristic (ROC) curve (AUC) of ST for predicting the incidence of PHLF was 0.754 (95% confidence interval (CI) 0.667 to 0.841; P < 0.001), with a sensitivity of 57.1% and a specificity of 82.5%, which were significantly greater than those of the ICG R15 level (AUC 0.670; 95% CI 0.560 to 0.779; P < 0.001). The critical value of ST was 43.5 mm. CONCLUSIONS: ST, which is an easy, inexpensive, and routinely available perioperative marker, showed a favorable predictive value for postoperative outcomes in HBV-associated HCC patients.


Assuntos
Carcinoma Hepatocelular/cirurgia , Falência Hepática/epidemiologia , Neoplasias Hepáticas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Baço/patologia , Adulto , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Hepatectomia/efeitos adversos , Vírus da Hepatite B/isolamento & purificação , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Fígado/cirurgia , Fígado/virologia , Falência Hepática/etiologia , Testes de Função Hepática , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Veia Porta/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Baço/diagnóstico por imagem
5.
Oncotarget ; 8(45): 79953-79963, 2017 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-29108377

RESUMO

Purpose: This study aimed to compare the efficacy of induction-concurrent (IC-CCRT) with concurrent-adjuvant (CCRT-AC) chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated by intensity-modulated radiotherapy (IMRT). Materials and Methods: Data on 834 patients with newly diagnosed, non-metastatic stage III-IVA (except T3N0) NPC receiving either IC-CCRT or CCRT-AC between July, 2004 and December, 2014 were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes of matched patients between IC-CCRT and CCRT-AC were compared. Results: The median follow-up duration is 45.2 months (range, 1.07-145.4 months). Overall, 309 pairs were selected by PSM. Univariate analysis revealed the CCRT-AC group achieved significantly higher 3-year DFS (83.9% vs. 78.7 %; P = 0.014) and OS (87.6% vs. 87.0%; P = 0.031). Multivariate analysis also identified treatment group (IC-CCRT vs. CCRT-AC) as an independent prognostic factor for 3-year DFS (HR, 1.546; 95% CI, 1.113-2.149; P = 0.009) and OS (HR, 1.487; 95% CI, 1.035-2.136; P = 0.032). Subgroup analysis revealed IC-CCRT was a protective factor for DMFS (HR, 0.145; 95% CI, 0.043-0.488; P = 0.002) in stage III disease; however, it could adversely affected DFS (HR, 2.009; 95% CI, 1.316-3.065; P = 0.001), OS (HR, 1.671; 95% CI, 1.060-2.636; P = 0.027) and DMFS (HR, 1.986; 95% CI, 1.155-3.416; P = 0.013) in stage IVA disease. Conclusions: CCRT-AC may be a more effective treatment modality in patients with stage IVA NPC disease, while IC-CCRT was superior in stage III disease.

6.
Oral Oncol ; 69: 26-32, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28559017

RESUMO

OBJECTIVES: Intensity-modulated radiotherapy (IMRT) has been applied in nasopharyngeal carcinoma (NPC) for nearly twenty years, while little is known about the ten-year survival outcomes. This study aimed at evaluating the 10-year survival outcomes for patients with NPC receiving IMRT. MATERIALS AND METHODS: Data on 614 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2004 and 2008 were retrospectively reviewed. Survival outcomes stratified by tumor stage were compared. RESULTS: The median follow-up duration was 112.7months (range, 7.6-156.8months) for the entire cohort. The 10-year local relapse-free survival rates for T1, T2 and T3 were 94.2%, 92.5% and 91.4% (P>0.05), respectively, and significantly higher than that of T4 disease (79.3%, P<0.05 for all rates). As N category increased from N0 to N3, the 10-year distant metastasis-free survival rates significantly decreased accordingly (P<0.01 for all rates). Furthermore, the 10-year overall survival rates were 100%, 87.1%, 75.5% and 55.6% for stage I, II, III and IV, respectively (P<0.05 except stage I and II). Multivariate analysis established tumor stage and age as independent prognostic factors. Late toxicities were assessable for 495 (80.6%) patients and most were Grade I/II damages. Xerostomia (387 of 489, 79.1%) and hearing impairment (212 of 495, 42.8%) remained the most troublesome. CONCLUSION: IMRT could achieve satisfactory survival outcomes for NPC patients with acceptable late toxicities. However, distant control still remains poor, especially for patients with N3 disease.


Assuntos
Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada , Taxa de Sobrevida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/tratamento farmacológico , Prognóstico , Adulto Jovem
7.
Hepatobiliary Pancreat Dis Int ; 15(6): 640-646, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27919854

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by a poor prognosis. Despite intensive research, markers for the early diagnosis, prognosis, and targeting therapy of PDAC are not available. This study aimed to investigate the protein expressions of Jagged1 and DLL4 in PDAC tumor, benign pancreatic and normal pancreatic tissues, and analyze the associations of the two proteins with the clinical and pathological characteristics of PDAC. METHODS: A total of 106 PDAC tumor tissues and 35 peritumoral tissues were collected from January 2000 to December 2011 at our hospitals. Thirteen normal pancreatic tissues and 55 benign pancreatic specimens were collected at the same period. Immunohistochemical staining was used to measure Jagged1 and DLL4 protein expressions in these tissues. RESULTS: The percentage of positive Jagged1 and DLL4 was significantly higher in PDAC than in normal pancreatic tissues, benign pancreatic tissues, and peritumoral tissues (P<0.01). The higher Jagged1 and DLL4 expressions in PDAC were significantly associated with poor differentiation, maximum tumor size >5 cm, invasion, regional lymph node metastasis, and TNM III/IV disease (P<0.05). In PDAC, Jagged1 expression positively correlated with DLL4 expression. Univariate Kaplan-Meier analysis showed that positive Jagged1 and DLL4 expressions were significantly associated with shorter survival in patients with PDAC. Multivariate Cox regression analysis showed that positive Jagged1 and DLL4 expressions were independent prognostic factors for poor prognosis of patients with PDAC. CONCLUSION: Positive Jagged1 and DLL4 expression is closely correlated with severe clinicopathological characteristics and poor prognosis in patients with PDAC.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Ductal Pancreático/química , Peptídeos e Proteínas de Sinalização Intercelular/análise , Proteína Jagged-1/análise , Neoplasias Pancreáticas/química , Adulto , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de Tempo , Regulação para Cima
8.
Sci Rep ; 6: 26378, 2016 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-27210263

RESUMO

We investigated the incidence of temporal lobe injury (TLI) in 132 nasopharyngeal carcinoma (NPC) patients who had undergone intensity-modulated radiotherapy (IMRT) in our hospital between March 2005 and November 2009; and identified significant dosimetric predictors of TLI development. Contrast-enhanced lesions or cysts in the temporal lobes, as detected by magnetic resonance imaging (MRI), were regarded as radiation-induced TLIs. We used the least absolute shrinkage and selection operator (LASSO) method to select Dmax (the maximum point dose) and the D1cc (the top dose delivered to a 1-mL volume) from 15 dose-volume-histogram-associated and four clinically relevant candidate factors; the Dmax and the D1cc were the most significant predictors of TLI development. We drew dose-response curves for Dmax and D1cc. The tolerance dose (TD) for the 5% and 50% probabilities of TLI development were 69.0 ± 1.6 and 82.1 ± 2.4 Gy for Dmax and 62.8 ± 2.2 and 80.9 ± 3.4 Gy for D1cc, respectively. The incidence of TLI in NPC patients after IMRT was higher than expected because the therapeutic window is narrow. High-quality longitudinal studies are needed to gain further insight into the complex spatiotemporal effects of non-uniform irradiation on TLI development in NPC patients.


Assuntos
Encefalopatias/epidemiologia , Carcinoma/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Radioterapia de Intensidade Modulada/efeitos adversos , Lobo Temporal/lesões , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Encefalopatias/diagnóstico por imagem , Encefalopatias/etiologia , Criança , Relação Dose-Resposta à Radiação , Feminino , Humanos , Incidência , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Radiometria , Dosagem Radioterapêutica , Estudos Retrospectivos , Lobo Temporal/efeitos da radiação , Resultado do Tratamento , Adulto Jovem
9.
Fluids Barriers CNS ; 12: 4, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25879623

RESUMO

BACKGROUND: Undisturbed functioning of the blood-brain barrier (BBB) crucially depends on paracellular signaling between its associated cells; particularly endothelial cells, pericytes and astrocytes. Hypoxic and ischemic injuries are closely associated with disturbed BBB function and the contribution of perivascular cells to hypoxic/ischemic barrier regulation has gained increased attention. Regardless, detailed information on the basal hypoxic/ischemic responses of the barrier-associated cells is rare and the outcome of such cell-specific responses on BBB modulation is not well understood. This study investigated crucial parameters of hypoxic/ischemic adaptation in order to characterize individual perivascular cell responses to stress conditions. METHODS: The brain microvascular endothelial cell line RBE4 (EC cell line) as well as primary rat brain endothelial cells (ECs), pericytes (PCs) and astrocytes (ACs) were exposed to 24 and 48 hours of oxygen deprivation at 1% and 0.2% O2. All primary cells were additionally subjected to combined oxygen and glucose deprivation mimicking ischemia. Central parameters of cellular adaptation and state, such as HIF-1α and HIF-1 target gene induction, actin cytoskeletal architecture, proliferation and cell viability, were compared between the cell types. RESULTS: We show that endothelial cells exhibit greater responsiveness and sensitivity to oxygen deprivation than ACs and PCs. This higher sensitivity coincided with rapid and significant stabilization of HIF-1α and its downstream targets (VEGF, GLUT-1, MMP-9 and PHD2), early disruption of the actin cytoskeleton and metabolic impairment in conditions where the perivascular cells remain largely unaffected. Additional adaptation (suppression) of proliferation also likely contributes to astrocytic and pericytic tolerance during severe injury conditions. Moreover, unlike the perivascular cells, ECs were incapable of inducing autophagy (monitored via LC3-II and Beclin-1 expression) - a putative protective mechanism. Notably, both ACs and PCs were significantly more susceptible to glucose than oxygen deprivation with ACs proving to be most resistant overall. CONCLUSION: In summary this work highlights considerable differences in sensitivity to hypoxic/ischemic injury between microvascular endothelial cells and the perivascular cells. This can have marked impact on barrier stability. Such fundamental knowledge provides an important foundation to better understand the complex cellular interactions at the BBB both physiologically and in injury-related contexts in vivo.


Assuntos
Adaptação Fisiológica , Barreira Hematoencefálica/fisiopatologia , Isquemia Encefálica/fisiopatologia , Hipóxia Encefálica/fisiopatologia , Actinas/metabolismo , Animais , Astrócitos/metabolismo , Astrócitos/fisiologia , Autofagia , Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/metabolismo , Hipóxia Celular , Linhagem Celular , Células Endoteliais/metabolismo , Células Endoteliais/fisiologia , Expressão Gênica , Hipóxia Encefálica/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Pericitos/metabolismo , Pericitos/fisiologia , Ratos
10.
Lung Cancer ; 84(1): 7-12, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24548340

RESUMO

BACKGROUND AND PURPOSE: Hypofractionated radiotherapy has been the principal curative treatment option for early stage NSCLC patients who are medically inoperable or those who refuse surgery and achieved favorable clinical outcomes. Evidence demonstrated that the linear quadratic model widely used in normally fractionated radiotherapy cannot work well to fit outcome data by use of BED to predict the effect of hypofractionation schemes. New models and the related metrics need to be developed to quantify the effect of high-dose ablative regimens for early stage NSCLC. PATIENTS AND METHODS: Trials using hypofractionated radiotherapy without chemotherapy to treat early stage (T1 or T2N0M0) primary NSCLC and providing information on patient numbers, age, T stage and local control rates were eligible. The endpoint was local relapse and the covariates analyzed were total radiotherapy dose, dose per fraction or combinations of the two parameters, treatment duration, T stage and median age of patients within the trial. The model used was a multivariate logistic regression. RESULTS: 19 trials were included (767 patients) in which 90 patients suffered local relapse. Only total dose × dose per fraction (D × d) and stage T had statistically significant effect on local control. Smaller T stage (p=0.000) and increasing D × d (p=0.006) were associated with improved probability of local control. In contrast, BED10 had no significant impact on local control, which probably indicated that D × d might be a more effective metric than BED10 to predict tumor control rate and assess the efficacy of the large dose fractionation schemes for early stage NSCLC. CONCLUSIONS: BED was not an ideal metric to estimate the effect of the schemes of high-dose ablative radiotherapy for early stage NSCLC, and total dose × fraction dose could be considered as a comparable index, though the result need to be further validated.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Fracionamento da Dose de Radiação , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Dosagem Radioterapêutica , Relação Dose-Resposta a Droga , Humanos , Estadiamento de Neoplasias , Resultado do Tratamento
11.
Vaccine ; 28(32): 5370-6, 2010 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-20573581

RESUMO

Mucosal immune responses act as the first line of defense against dental caries. In this study, an optimal vaccination strategy was developed to enhance anti-caries mucosal immune responses. Mice and rats were vaccinated intranasally firstly with plasmid pCIA-P encoding PAc antigen of Streptococcus mutans and then with rPAc, or with pCIA-P for twice, or with rPAc protein for twice, respectively. The potential of inducing mucosal and systemic immune responses to special antigens was measured by ELISA. In addition, antibody type, cytokine production and protection effectiveness against dental caries were also evaluated. Although all immunized groups developed immune responses, the antibody responses in the DNA prime-protein boost group were stronger compared with those elicited by either the DNA vaccine or the protein vaccine. In particular, the Th1-biased response that was established by the DNA immunization was diverted to Th1/Th2-mixed response following the rPAc protein boost. Moreover, protection against S. mutans challenge was obtained in the rats treated with the DNA prime-protein boost regimen, as shown by a significant reduction in dental caries lesion, compared with the control groups immunized with the DNA or protein only. All these findings may provide useful information about effective mucosal vaccines against dental caries.


Assuntos
Cárie Dentária/prevenção & controle , Infecções Estreptocócicas/prevenção & controle , Vacinas Estreptocócicas/imunologia , Streptococcus mutans/imunologia , Vacinas de DNA/imunologia , Administração Intranasal , Animais , Anticorpos Antibacterianos/sangue , Formação de Anticorpos , Proteínas de Bactérias/imunologia , Citocinas/análise , Cárie Dentária/imunologia , Feminino , Imunidade Celular , Imunidade nas Mucosas , Imunização Secundária , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/imunologia , Organismos Livres de Patógenos Específicos , Infecções Estreptocócicas/imunologia
12.
Surgery ; 146(5): 854-60, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19744458

RESUMO

BACKGROUND: Isolated segmentectomy VIII is a technically demanding operative procedure and is reported only rarely. To our knowledge, no reports on anatomic segmentectomy based on an intrahepatic approach have been described. For cirrhotic patients with hepatocellular carcinoma (HCC) limited to segment VIII, this is a parenchyma-preserving hepatectomy that can be tolerated. METHODS: Eighteen patients with HCC underwent anatomic segment VIII segmentectomy from January 2005 to January 2008 in our institution. The operative techniques, postoperative, and oncologic outcomes were reviewed. RESULTS: Anatomic segmentectomy VIII was feasible with the technology described herein in all patients. The perioperative and oncologic outcomes were comparable with those of other similar hepatic resections. The median follow-up time was 28 months. The 3-year survival rate was 65%. CONCLUSION: Although complex and technically demanding, an intrahepatic Glissonian approach for anatomic segmentectomy of segment VIII is an oncologically radical but parenchyma-sparing hepatic resection. In terms of preserving greater functioning liver parenchyma, it may be a safe and effective alternative to extensive hepatectomy.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/complicações , Feminino , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
13.
Hepatogastroenterology ; 56(96): 1730-4, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20214226

RESUMO

BACKGROUND/AIMS: Intraoperative bleeding remains a major concern during mesohepatectomy because of doubled area of cut surface and proximity to important intrahepatic vascular structures. Preliminary extrahepatic exposure and looping of the main hepatic veins with the possibility of clamping them in association with total or partial vascular inflow occlusion, can lead to substantially reducing intraoperative bleeding. METHODOLOGY: From January 2003 to July 2008, preliminary exposure and looping of the main hepatic veins was performed in 67 patients undergoing mesohepatectomy. Among these patients, mesohepatectomy was performed with clamping of more than one of the main hepatic veins in 47 patients. We report the results obtained in those patients. RESULTS: Total vascular inflow occlusion with Pringle maneuver or partial vascular inflow occlusion based on an intrahepatic approach was used in all patients. The amount of intraoperative blood loss averaged (580 +/- 308) (range 180 to 4500) ml. No macroscopic tumor residue was encountered. There were no hospital deaths and the morbidity rate was 25.7%. The mean hospital stay was 11.2 days (range, 9-26). CONCLUSIONS: Our study showed that preliminary extrahepatic control of the main hepatic veins was a safe and technically feasible maneuver. During mesohepatectomy, clamping more than one of the main hepatic veins, in association with total or partial vascular inflow occlusion, is efficacious in reducing intraoperative bleeding.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Veias Hepáticas , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Eur J Oral Sci ; 116(4): 319-23, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18705799

RESUMO

Matrix metalloproteinase-1 (MMP-1) 1G/2G (-1,607) polymorphisms have been identified and shown to influence the transcription of the MMP-1 gene. In order to compare the expression of MMP-1 with different MMP-1 gene promoter alleles after force loading, human periodontal ligament (PDL) cells were cultured and genotyped into three alleles by polymerase chain reaction and restriction endonuclease cleavage. The three genotypes of PDL cells were centrifuged and the expression of MMP-1 mRNA and protein were determined by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that centrifugal force upregulated the expression of both MMP-1 mRNA and protein in all three genotypes of PDL cells. The induction of MMP-1 by force was significantly greater in cells with a 2G/2G genotype or a 1G/2G genotype than in cells homozygous for the 1G allele. The MMP-1 mRNA and protein levels were significantly higher for cells with the 2G allele than for cells with the 1G/2G allele or the 1G allele. These results suggest that a single nucleotide polymorphism in the -1,607 bp MMP-1 promoter region might be associated with the difference observed in the endogenous expression of MMP-1 in PDL cells under mechanical force.


Assuntos
Análise do Estresse Dentário , Metaloproteinase 1 da Matriz/biossíntese , Metaloproteinase 1 da Matriz/genética , Ligamento Periodontal/enzimologia , Adolescente , Alelos , Células Cultivadas , Centrifugação , Feminino , Genótipo , Humanos , Metaloproteinase 1 da Matriz/análise , Ligamento Periodontal/citologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
17.
J Ocul Pharmacol Ther ; 21(6): 445-53, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16386086

RESUMO

Timolol-loaded poly(D,L-lactide-co-glycolide; PLGA) films were prepared for achieving the long-term intraocular pressure (IOP) lowering effect on glaucoma treatment. The physicochemical properties and in vivo effects of films were determined and characterize the delivery system. PLGA, span 20, propylene glycol (PG), and timolol base were dissolved in dichloromethane (DCM) and kept in a stainless mold; timolol films were prepared after the evaporation of DCM. Timolol disc-shape film preparation (TDF), containing 1 mg of timolol in 0.37 cm(2) area, was fabricated by using a trephine and placed onto the cul de sac of alpha-chymotrypsin-induced ocular hypertension rabbits for assessing the IOP lowering effect. The prepared films characterized a Young's modulus ranged from 1.13 to approximately 2.49 MPa, and related to the content percentages of PLGA, PG, and the residual DCM. The timolol film could maintain drug release for 1 week. Following a single-dose application in ocular hypertension rabbits, the prepared TDF could achieve a long-term IOP lowering effect and maintain the IOP change (in comparison with baseline) of approximately 7 mmHg within 1 week. The aqueous humor levels of timolol were low within a range of 0.8 to approximately 0.24 microg/mL for the initial 24 h and less than 0.15 microg/mL for 4-7 days. The investigated film formulation might be potentially developed for the application of long-term ocular delivery systems.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Pressão Intraocular/efeitos dos fármacos , Hipertensão Ocular/tratamento farmacológico , Poliglactina 910/química , Timolol/uso terapêutico , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/química , Antagonistas Adrenérgicos beta/farmacocinética , Animais , Humor Aquoso/efeitos dos fármacos , Humor Aquoso/metabolismo , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Masculino , Hipertensão Ocular/fisiopatologia , Coelhos , Solubilidade , Propriedades de Superfície , Resistência à Tração , Fatores de Tempo , Timolol/administração & dosagem , Timolol/química , Timolol/farmacocinética , Resultado do Tratamento
18.
Ai Zheng ; 23(11): 1325-8, 2004 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-15522183

RESUMO

BACKGROUND & OBJECTIVE: Waldeyer's ring is the most vulnerable site outside lymph nodes in non-Hodgkin's lymphoma (NHL). Its imaging features in NHL of early stage were similar with those of squamous epithelial cancer, which often leads to misdiagnosis. This study was to discuss imaging features of Waldeyer's ring in NHL, and its clinical significance. METHODS: CT and MRI performances of 149 patients with pathologically diagnosed Waldeyer's ring-NHL were retrospectively analyzed. RESULTS: Among 149 cases of Waldeyer's ring-NHL, 98 (65.8%) were B-cell origin, and 51 (34.2%) were T-cell or NK/T-cell origin; tonsil was the most vulnerable site followed by nasopharyngeal tonsil and other positions. CT and MRI showed that 81 were focal nodules or masses (commonly in B-cell NHL), 36 were diffuse infiltrating growth (commonly in NK/T-cell NHL), 7 were pure ulcer, and 25 were mixed type. The lesions of focal masses are characterized with even CT density and MRI signals. The lesions usually localized in pharynx-mucosa clearance, but rarely in deep space, such as parapharyngeal space, and in skull-base. Among 78 cases with involved cervical lymph nodes, 64 were B-cell origin, and 14 were NK/T-cell origin (P< 0.05). CONCLUSION: Multiple positions and centers origin, huge masses, diffuse infiltration growth, and less involvement in deep space and skull-base are typical imaging features of Waldeyer's ring-NHL; CT and MRI may be helpful to diagnose, clinical classifying, and treating Waldeyer's ring-NHL.


Assuntos
Linfoma não Hodgkin/diagnóstico , Imagem por Ressonância Magnética , Neoplasias Nasofaríngeas/diagnóstico , Tomografia Computadorizada por Raios X , Neoplasias Tonsilares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Linfonodos/patologia , Linfoma de Células B/diagnóstico , Linfoma de Células B/diagnóstico por imagem , Linfoma não Hodgkin/classificação , Linfoma não Hodgkin/diagnóstico por imagem , Linfoma de Células T/diagnóstico , Linfoma de Células T/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Pescoço , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Nasais/patologia , Estudos Retrospectivos , Neoplasias Tonsilares/diagnóstico por imagem
19.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 29(4): 438-40, 2004 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-16134599

RESUMO

OBJECTIVE: To study the expression of ER mRNA, presenilin 2 (PS2) and their relationship and clinicopathological significance in the pancreatic carcinoma. METHODS: The assay of ER mRNA was detected by in situ hybridization technique and the expression of PS2 was completed by immunohistochemical method of avidin-biotin complex in the 10% neutral formalin-fixed and routinely paraffin-embedded sections of specimen with pancreatic carcinoma. RESULTS: The positive rate and the score of PS2 were 45.7% and 1.82 +/- 1.34, also those of ER mRNA were 51.4% and 2.08 +/- 1.46 in 35 patients with pancreatic carcinoma. The highly positive correlations were found among the positive rate and the score of ER mRNA and PS2. The positive rate and the score were significantly higher in the cases of well-differentiated adenocarcinoma without metastasis than those in the ones of middle- or poorly-differentiated adenocarcinoma with metastasis. CONCLUSION: The expression of ER mRNA or PS2 might reflect the biological behaviors and hormone-dependent status of pancreatic carcinoma. The assay of ER mRNA and meanwhile the detection of PS2 might have important clinical values for better understanding sex-hormone dependence and raising the therapeutic effect of clinical endocrine therapy of the pancreatic carcinoma.


Assuntos
Adenocarcinoma/metabolismo , Proteínas de Membrana/biossíntese , Neoplasias Pancreáticas/metabolismo , Receptores Estrogênicos/biossíntese , Adulto , Feminino , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Presenilina-2 , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptores Estrogênicos/genética
20.
Zhonghua Wai Ke Za Zhi ; 41(4): 267-70, 2003 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-12882669

RESUMO

OBJECTIVE: To find the distribution of nanobacteria in the serum, bile and gallbladder mucosa of cholecystolithiasis patients. METHODS: The infection rate of nanobacteria was identified by ELISA in the serum samples from 338 healthy people and 76 patients with cholecystolithiasis (chi(2) = 0.89, P > 0.05). Nanobacteria were cultured from the bile samples in 57 patients with cholecystolithiasis and 18 non-cholelithiasis patients and identified by immunohistochemical staining and TEM (chi(2) = 29.80, P < 0.05). Forty samples of gallbladder mucosa randomly selected from the 57 cholecystolithiasis patients were identified by immunohistochemical staining and compared with the corresponding bile samples. RESULTS: The infection rate of nanobacteria was 8.0% and 31.6% for the serum samples of the healthy people and cholecystolithiasis patients, respectively. The positive rate of nanobacteria in the bile samples was 61.3% and there was no significant difference in the bile of the cholecystolithiasis patients and the control group (61.4% vs. 61.1%). Fourteen positive patients had infection of nanobacteria in the gallbladder mucosa, submucosa, and calcific field. CONCLUSIONS: The infection rate of nanobacteria was 8% in the serum samples from the healthy people. There are nanobacteria in the serum, bile, and gallbladder mucosa. The infection of the nanobacteria may result in calcification and fibrosis of the gallbladder.


Assuntos
Bactérias/isolamento & purificação , Bile/microbiologia , Colecistolitíase/sangue , Colecistolitíase/microbiologia , Vesícula Biliar/microbiologia , Adulto , Bactérias/ultraestrutura , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Transmissão , Pessoa de Meia-Idade , Membrana Mucosa/microbiologia , Adulto Jovem
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