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1.
Zhonghua Wai Ke Za Zhi ; 61(9): 788-794, 2023 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-37491172

RESUMO

Objectives: To investigate the factors influencing the height of anterior peritoneal reflection (APR) for patients with rectal cancer, and to analyze the relationship between the APR and the lateral lymph node metastasis. Methods: Clinical data of 432 patients with tumor located within and below APR were retrospectively collected from the rectal cancer database at the Department of General Surgery, Peking Union Medical College Hospital from August 2020 to September 2022. Ninty-eight non-rectal cancer patients were also enrolled as a control group. There were 308 males and 124 females in the tumor group, aged (M(IQR)) 62 (16) years (range: 24 to 85 years) and 53 males and 45 females in the control group, aged 60 (22) years (range: 27 to 87 years). The APR height, pelvis, and tumor-related parameters were measured by MRI. A multifactor linear regression model was established to analyze the dependent correlation factors of APR height. These factors of the two groups were matched by propensity score matching and their APR heights were compared after matching. An ordinal Logistic regression model was established to explore the relationship between APR-related parameters and radiographic lateral lymph node metastasis. Results: The APR height of the tumor group was (98.7±14.4) mm (range: 43.3 to 154.0 mm) and the control group was (95.1±12.7) mm (range: 68.0 to 137.9 mm). Multivariable linear regression revealed that the greater the weight (B=0.519, 95%CI: 0.399 to 0.640, P<0.01), the anterior pelvic depth (B=0.109, 95%CI: 0.005 to 0.213, P=0.039) and the smaller the bi-ischial diameter (B=-0.172, 95%CI:-0.294 to -0.049, P=0.006), the higher the APR height. The tumor group had a higher APR height than the control group after propensity score matching ((98.3±14.2) mm vs. (95.1±12.7) mm, t=-1.992, P=0.047). Ordinal Logistic regression indicated that the longer segment of the tumor invade the nonperitoneal rectum was an independent influencing factor of radiographic lateral lymph node metastasis (OR=1.016, 95%CI: 1.002 to 1.030, P=0.021), while the distance between the anal verge and the tumor was not (OR=0.986, 95%CI: 0.972 to 1.000, P=0.058). Conclusions: The higher the weight, the deeper and narrower the pelvis, the higher the APR height. There is a certain relationship between APR and lateral lymph node metastasis on imaging.

2.
Acta Gastroenterol Belg ; 84(1): 51-56, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33639693

RESUMO

Background and study aims: To investigate the safety and efficacy of splenectomy for hepatolenticular degeneration (HLD) patients with PLT less than 20 × 109/L. Patients and methods: A total of 244 HLD patients with hypersplenism underwent splenectomy. According to the preoperative PLT values, the patients were divided into three groups : group A of 53 patients with PLT < 20 × 109/L ; group B of 92 patients with 20 × 109/L ≤ PLT ≤ 30 × 109/L ; group C of 99 patients with PLT > 30 × 109/L. General information including : blood cell counts, liver function , coagulation function 1 day before sugery and 1, 7, 14 days after surgery ; intraoperative blood loss ; operation time ; vital signs at the beginning, at 60 minutes and the end of the operation. Pressure and blood oxygen ; postoperative drainage ; postoperative complications and mortality. Results: Blood cell counts, liver function, and coagulation function were improved after splenectomy in three groups (P<0.05) ; there was no significant difference in blood loss, operation time, vital signs during the operation, postoperative drainage, postoperative complications and mortality between three groups (P>0.05). Conclusion: For HLD patients with hypersplenism, it is safe and effective to conduct splenectomy under PLT < 20 × 109/L.


Assuntos
Degeneração Hepatolenticular , Hiperesplenismo , Laparoscopia , Humanos , Hiperesplenismo/etiologia , Hiperesplenismo/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Esplenectomia , Resultado do Tratamento
3.
Clin Radiol ; 76(1): 81.e11-81.e19, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32962807

RESUMO

AIM: To evaluate the imaging characteristics of simultaneous multi-slice (SMS) accelerated diffusion-weighted imaging (DWI) with decreased section thickness, with and without motion correction, in comparison to conventional DWI (cDWI) for the detection of lesions in patients with neuroendocrine tumour (NET) liver metastases. MATERIALS AND METHODS: Fifteen patients with NET liver metastases underwent cDWI (section thickness [SL]=4 mm) and SMS-DWI (SL=2 mm). Non-linear motion-corrected (Moco)-SMS-DWI was generated in addition to the original series. Qualitative imaging characteristics (five-point Likert scale), the number of high signal lesions, and the detectability and delineation of lesions were evaluated and compared using the Friedman and the Dunn-Bonferroni tests. The test-retest variability (TRV) of the cDWI and SMS-DWI techniques was investigated among 11 healthy volunteers who underwent cDWI (SL=4 mm) and SMS-DWI (SL=4 mm) twice. The Friedman and the Dunn-Bonferroni post-hoc tests were used to compare the mean apparent diffusion coefficient (ADC) and the TRV in different liver regions between the three series. RESULTS: Moco-SMS-DWI demonstrated significantly superior overall image quality (p<0.001) with significantly fewer artefacts (p=0.003) than cDWI. The number of lesions detected by cDWI, SMS-DWI, and Moco-SMS-DWI were 348, 504, and 523, respectively. The detectability and delineation of the lesions and the ADC values were significantly higher on the SMS-DWI and Moco-SMS-DWI images than on the cDWI images (all p<0.001). Moco-SMS-DWI showed significantly higher TRV than cDWI in regions near the liver edge (p=0.018). CONCLUSIONS: SMS-DWI achieves higher spatial resolution than cDWI within the same acquisition time, detects more lesions, and provides better lesion delineation. By applying motion correction, the TRV of DWI could be enhanced in regions near the liver edge.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/patologia , Adulto , Idoso , Estudos de Casos e Controles , Meios de Contraste , Ácido Edético , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Estudos Prospectivos , Reprodutibilidade dos Testes
4.
QJM ; 113(12): 870-875, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32407476

RESUMO

BACKGROUND: Hydrogen was proven to have anti-oxidative and anti-inflammation effects to various diseases. AIM: We wish to investigate the acute effects of inhaled hydrogen on airway inflammation in patients with asthma and chronic obstructive pulmonary disease (COPD). DESIGN: Prospective study. METHODS: In total, 2.4% hydrogen containing steam mixed gas (XEN) was inhaled once for 45 min in 10 patients with asthma and 10 patients with COPD. The levels of granulocyte-macrophage colony stimulating factor, interferon-γ, interleukin-1ß (IL-1ß), IL-2, IL-4, IL-6 and so on in peripheral blood and exhaled breath condensate (EBC) before and after 'XEN' inhalation were measured. RESULTS: 45 minutes 'XEN' inhalation once decreased monocyte chemotactic protein 1 level in both COPD (564.70-451.51 pg/mL, P = 0.019) and asthma (386.39-332.76 pg/mL, P = 0.033) group, while decreased IL-8 level only in asthma group (5.25-4.49 pg/mL, P = 0.023). The level of EBC soluble cluster of differentiation-40 ligand in COPD group increased after inhalation (1.07-1.16 pg/mL, P = 0.031), while IL-4 and IL-6 levels in EBC were significantly lower after inhalation in the COPD (0.80-0.64 pg/mL, P = 0.025) and asthma (0.06-0.05 pg/mL, P = 0.007) group, respectively. CONCLUSIONS: A single inhalation of hydrogen for 45 min attenuated inflammatory status in airways in patients with asthma and COPD.


Assuntos
Asma/metabolismo , Citocinas/metabolismo , Hidrogênio/uso terapêutico , Inflamação/terapia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Administração por Inalação , Adulto , Idoso , Asma/fisiopatologia , Testes Respiratórios , Feminino , Gases/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fatores de Tempo , Adulto Jovem
5.
Neoplasma ; 66(2): 232-239, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30509108

RESUMO

Recent studies indicate that circular RNA (circRNA) is involved in tumorigenesis, but its role in triple-negative breast cancer (TNBC) remains largely unknown. In this study, we characterized the role of circ-ITCH in TNBC and found that circ-ITCH was significantly down-regulated in TNBC tissues and cell lines and closely associated with poor prognosis. We therefore constructed the MDA-MB-231 and BT-549 TNBC cell lines stably expressing circ-ITCH by lentiviral vectors to determine its underlying mechanisms in TNBC progression. Most importantly, over-expression of circ-ITCH remarkably inhibited TNBC proliferation, invasion and metastasis both in vitro and in vivo. Mechanistically, we found that circ-ITCH acts as a sponge for miR-214 and miR-17 to increase expression of its ITCH linear isoform, thereby inactivating Wnt/ß-catenin signaling. Our combined results show for the first time that circ-ITCH is a tumor suppressor, a promising prognostic biomarker in TNBC and that its restoration could well be a successful strategy in TNBC.


Assuntos
RNA/genética , Proteínas Repressoras/genética , Neoplasias de Mama Triplo Negativas/genética , Ubiquitina-Proteína Ligases/genética , Via de Sinalização Wnt , Apoptose , Linhagem Celular Tumoral , Humanos , MicroRNAs/genética , RNA Circular , Neoplasias de Mama Triplo Negativas/patologia
6.
J Viral Hepat ; 24(12): 1114-1120, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-20819148

RESUMO

Smoking may be a risk factor for diabetes, and it has been suggested that viral hepatitis may predispose to diabetes. We studied diabetes and smoking histories in people with viral hepatitis. From 1997 to 2004, we studied the risk of incident diabetes in a community cohort with hyperendemic HBV and HCV infection in southern Taiwan. The cohort involved 3539 people (40-70 years old) without diabetes. Four hundred and twenty-three individuals developed diabetes. Those who were ≥65 years old, frequently consumed alcohol, had a BMI ≥25, had <9 years of education, were anti-HCV+ or smoked ≥1 pack per day were more likely to develop diabetes (P < 0.05). A cumulative hazard function test showed that the higher the smoking levels, the greater the cumulative incidence rate of diabetes in HBsAg+ participants only (P = 0.03 by log-rank test). A multiple Cox proportional hazards model analysis in different hepatitis statuses showed smoking levels were strong predictors of diabetes with a dose-response relationship for type 2 diabetes in those with HBsAg+ : hazard ratio (HR) = 3.8, (95% CI: 1.2, 12.3) for light smokers (<1 pack per day) and HR = 4.4 (95% CI: 1.5, 13.3) for heavy smokers (≥1 pack per day). Increasing BMI was a common predictor in all people. Smoking is a strong predictor for diabetes with a dose-response relationship in HBsAg+ individuals and a mild predictor for seronegative individuals but not significant in anti-HCV+ individuals.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Fumar/efeitos adversos , Adulto , Idoso , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taiwan/epidemiologia
7.
Zhonghua Nei Ke Za Zhi ; 55(12): 979-982, 2016 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-27916060

RESUMO

Chronic diarrhea is a common complaint in gastroentology department, which is classified into a variety of types. While as eosinophilic gastroenteritis is a rare cause. A 50-year-old male patient was admitted with a 2-year history of diarrhea worsened for 10 months. Fasting could alleviate the diarrhea. Laboratory findings demonstrated anemia, low vitamins and minerals, fat malabsorption and abnormal D-xylose absorption test, delayed gastric emptying. According to the endoscopic biopsy of gastrointestinal mucosa, the diagnosis of eosinophilic gastroenteritis was made. Diabetic neuropathy may aggravate the symptom. The diarrhea resolved after the administration of steroids.


Assuntos
Diabetes Mellitus , Diarreia , Enterite/diagnóstico por imagem , Enterite/patologia , Eosinofilia/diagnóstico por imagem , Eosinofilia/patologia , Gastrite/diagnóstico por imagem , Gastrite/patologia , Gastroenterite/diagnóstico por imagem , Gastroenterite/patologia , Redução de Peso , Biópsia , Diarreia/diagnóstico , Diarreia/tratamento farmacológico , Endoscopia , Endoscopia do Sistema Digestório , Gastroenterite/terapia , Humanos , Masculino , Gastropatias
8.
Bone Joint J ; 98-B(6): 834-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27235529

RESUMO

AIM: Many aspects of the surgical treatment of patients with tuberculosis (TB) of the spine, including the use of instrumentation and the types of graft, remain controversial. Our aim was to report the outcome of a single-stage posterior procedure, with or without posterior decompression, in this group of patients. PATIENTS AND METHODS: Between 2001 and 2010, 51 patients with a mean age of 62.5 years (39 to 86) underwent long posterior instrumentation and short posterior or posterolateral fusion for TB of the thoracic and lumbar spines, followed by anti-TB chemotherapy for 12 months. No anterior debridement of the necrotic tissue was undertaken. Posterior decompression with laminectomy was carried out for the 30 patients with a neurological deficit. RESULTS: The mean kyphotic angle improved from 26.1° (- 1.8° to 62°) to 15.2° (-25° to 51°) immediately after the operation. At a mean follow-up of 68.8 months (30 to 144) the mean kyphotic angle was 16.9° (-22° to 54°), with a mean loss of correction of 1.6° (0° to 10°). There was a mean improvement in neurological status of 1.2 Frankel grades in those with a neurological deficit. Bony union was achieved in all patients, without recurrent infection. CONCLUSIONS: Long posterior instrumentation with short posterior or posterolateral fusion is effective in the treatment of TB spine. It controls infection, corrects the kyphosis, and maintains correction and neurological improvement over time. TAKE HOME MESSAGE: With effective anti-TB chemotherapy, a posterior only procedure without debridement of anterior lesion is effective in the treatment of TB spondylitis, and an anterior procedure can be reserved for those patients who have not improved after posterior surgery. Cite this article: Bone Joint J 2016;98-B:834-9.


Assuntos
Vértebras Lombares/cirurgia , Espondilite/terapia , Vértebras Torácicas/cirurgia , Tuberculose da Coluna Vertebral/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antituberculosos/uso terapêutico , Descompressão Cirúrgica , Quimioterapia Combinada , Etambutol/uso terapêutico , Humanos , Isoniazida/uso terapêutico , Cifose/etiologia , Cifose/cirurgia , Laminectomia , Vértebras Lombares/microbiologia , Pessoa de Meia-Idade , Pirazinamida/uso terapêutico , Estudos Retrospectivos , Rifampina/uso terapêutico , Fusão Vertebral , Espondilite/microbiologia , Vértebras Torácicas/microbiologia
9.
Acta Orthop Belg ; 83(3): 656-662, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-29119910

RESUMO

Ulnar shortening is a common procedure for treating ulnar wrist pain of various causes. Many tools and devices had been reported in the literature to facilitate the procedure, but not all are universally available. Freehand technique is still useful in clinical practice. Here we present a pre-drilled hole method to improve the outcomes of the freehand technique. From 2008 to 2012, a total of 51 patients at our institution underwent ulnar shortening with this method, with an -average follow-up period of 24.4 months (range, 12-62 months). The average shortening length was 4.6 mm (range, 3-8.5 mm). All patients had uneventful union at an average of 9.8 weeks (range, 8-14 weeks) after the surgery. All had improved functional results. All patients returned to their previous full level of work and activities. The pre-drilled hole method for ulnar shortening is an easy assist to the freehand technique. Also, the union rate is high, and complications are uncommon.


Assuntos
Artralgia/cirurgia , Osteotomia/métodos , Articulação do Punho/cirurgia , Seguimentos , Humanos , Resultado do Tratamento , Ulna
10.
J Hand Surg Eur Vol ; 40(7): 735-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26056128

RESUMO

UNLABELLED: We compared the short-term (3 months) and long-term (2 years) outcomes and complications of percutaneous release of 187 trigger digits of 154 patients treated between 2009 and 2012, all treated by a single surgeon. The 154 patients included 48 patients with diabetes mellitus and 106 non-diabetic patients. The only short-term complication was pain, occurring in three digits (5%) in the diabetic patients and six digits (5%) in the non-diabetic patients. The long-term complications were pain in 15 digits (25%) in the diabetic patients and 18 digits (14%) in the non-diabetic patients. This was not significant (p = 0.058). Recurrent triggering occurred in nine digits (15%) in the diabetic patients, which was significantly greater than the six digits (5%) in the non-diabetic patients (p = 0.013). The non-diabetic patients were significantly more satisfied. LEVEL OF EVIDENCE: level III.


Assuntos
Complicações do Diabetes , Dedo em Gatilho/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Satisfação do Paciente/estatística & dados numéricos , Recidiva , Dedo em Gatilho/complicações
11.
Anaesth Intensive Care ; 43(4): 473-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26099759

RESUMO

Five popular scoring systems for postoperative nausea and vomiting (PONV) were validated and compared with two new predictive models in a Taiwanese population. Nine hundred and ninety-two patients receiving general anaesthesia in a tertiary hospital were investigated in a prospective observational cohort study. Patient demographic data and the incidence of nausea or vomiting in the first 24 hours after surgery were recorded. The overall incidence of PONV was 42%. The area under the curve (AUC) of the five published PONV risk scoring systems was 0.62 to 0.67. Logistic regression analysis in this study cohort showed that female sex and a history of PONV/car sickness were the only statistically significant independent risk factors for PONV (likelihood ratio test P <0.001).The AUCs of our two-predictor and gender-only models were 0.668 and 0.643, respectively (Nagelkerke R² = 0.122 and 0.109). Goodness-of-fit showed that a two-predictor model predicted outcome that was in agreement with the observed outcome (P=0.973). Both the two-predictor model and the Apfel score had a similar AUC that was significantly different from the AUCs of the other models. The AUC for the gender-only model in our population was similar to that of the simplified Koivuranta and the Palazzo and Evans scores (AUC=0.659 and 0.632; P=0.137 and 0.513 respectively). All AUCs had only moderate discrimination power but our female gender-only model was much simpler. Using female gender as the only predictor of PONV had predictive power with 75% sensitivity and 54% specificity.


Assuntos
Anestesia Geral/efeitos adversos , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Área Sob a Curva , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Medição de Risco , Fatores de Risco , Sensibilidade e Especificidade , Fatores Sexuais , Taiwan
12.
Exp Clin Endocrinol Diabetes ; 123(2): 106-11, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25502845

RESUMO

OBJECTIVE: To investigate the plasma osteoprotegerin level and osteoprotegerin expression in renal biopsy tissue in type 2 diabetes with nephropathy. METHODS: Plasma osteoprotegerin level was measured by enzyme-linked immunoassay in 48 type 2 diabetes with normoalbuminuria, 48 patients with microalbuminuria, 44 patients with macroalbuminuria and 40 healthy persons. Part of diabetes patients with nephropathy were performed kidney biopsy by ultrasound guide. The osteoprotegerin expression in kidney biopsy tissue is examined by immunohistochemistry. RESULTS: The plasma osteoprotegerin levels were significantly elevated in patients with microalbuminuria (3.73±0.75 ng/l) and macroalbuminuria (4.68±0.82 ng/l) as compared with patients with normoalbuminuria (2.71±0.69 ng/l) and control subjects (2.11±0.42 ng/l). And the plasma osteoprotegerin level in macroalbuminuric group was also higher than that in microalbuminuria group. The plasma osteoprotegerin level had a positive correlation with the fasting plasma glucose (FPG), 2-h plasma glucose (2hPG), glycohemoglobinA1c (HbA1C), high sensitive C-reactive protein (hsCRP) and log(UAER). Multivariate regression analysis revealed that plasma osteoprotegerin level was an independent factor associated with albuminuria in type 2 diabetes. The immunohistochemistry results showed that positive immunostaining for osteoprotegerin was observed in the renal tubule cells of biopsy and not in glomerulus, and the osteoprotegerin expression was higher in macroalbuminuria group than that in microalbuminuria group. CONCLUSIONS: The plasma osteoprotegerin level and the osteoprotegerin expression in renal tubule cells of biopsy tissue were increased in nephropathy of type 2 diabetes. This finding supports the growing concept that osteoprotegerin may act as an important regulatory molecule in the angiopathy, and particularly, that it may be involved in the occurrence and development of nephropathy in type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Nefropatias Diabéticas/metabolismo , Rim/metabolismo , Osteoprotegerina/metabolismo , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Feminino , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Osteoprotegerina/sangue
13.
Genet Mol Res ; 13(2): 2978-86, 2014 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-24782132

RESUMO

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Ovarianas/genética , Animais , Biópsia , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Proteínas de Neoplasias/genética , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Gene Ther ; 18(4): 372-83, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21107437

RESUMO

The transcription factor Forkhead box O3 (Foxo3) has a critical role in suppressing the expansion of antigen-specific effector T-cell populations; hence, Foxo3 is a potential target for enhancing the antitumor immunity of cancer vaccines. In this report, we evaluated the potential of RNA interference (RNAi)-mediated silencing of Foxo3 in antigen-presenting cells as an adjuvant for HER2/neu DNA cancer vaccines. Bicistronic plasmids expressing the N-terminal extracellular domain of human HER-2/neu and the Foxo3 short hairpin RNA (hN'-neu-Foxo3 shRNA) or the scrambled control (hN'-neu-scramble shRNA) were subcutaneously injected into mice by gene gun administration to elicit antitumor immunity against p185neu-overexpressing MBT-2 bladder tumor cells. We found that mice treated with hN'-neu-Foxo3 shRNA showed greater reductions in tumor growth and longer survival times than mice treated with hN'-neu-scramble shRNA, indicating that the silencing of Foxo3 enhanced the antitumor efficacy of the HER-2/neu cancer vaccine. Cytotoxicity analyses further revealed that the Foxo3 shRNA-enhanced antitumor effect was associated with significant increases in the number of functional CD8(+) T cells and in the levels of cytotoxic T lymphocytes activity. Interleukin-6 was induced by hN'-neu-Foxo3 shRNA treatment but did not have a critical role in the antitumor effect of the hN'-neu-Foxo3 shRNA vaccine. Moreover, in vivo lymphocyte depletion analyses confirmed that the antitumor efficacy of the hN'-neu-Foxo3 shRNA vaccine depended on functional CD8(+) T cells. Finally, Foxo3 suppression was shown to markedly improve the effect of the HER-2/neu DNA vaccine in limiting the growth and lung metastases of MBT-2 cells. Overall, these results support RNAi-mediated silencing of Foxo3 as an effective strategy to enhance the therapeutic antitumor effect of HER-2/neu DNA vaccines against p185neu-positive tumors.


Assuntos
Células Apresentadoras de Antígenos/metabolismo , Vacinas Anticâncer/imunologia , Fatores de Transcrição Forkhead/genética , Genes erbB-2 , Interferência de RNA , Vacinas de DNA/imunologia , Animais , Células Apresentadoras de Antígenos/imunologia , Biolística , Linhagem Celular , Chlorocebus aethiops , Células Dendríticas/imunologia , Proteína Forkhead Box O3 , Vetores Genéticos , Humanos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/farmacologia , Linfócitos T/imunologia , Neoplasias da Bexiga Urinária/prevenção & controle
15.
Cytotherapy ; 10(4): 376-89, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18574770

RESUMO

BACKGROUND: Current efforts to direct differentiation of human embryonic stem cells (hESC) into a particular cell lineage usually lead to a heterogeneous cell population with only a fraction of the desired cell type present. We show the generation of an essentially pure population of human cardiomyocytes from hESC using lineage selection. METHODS: A construct comprising the murine alpha-myosin heavy chain (alpha-MHC) promoter driving the neomycin-resistance gene was introduced into hES3 cells to generate stable transgenic lines. Transgenic hESC lines were differentiated into cardiomyocytes and subjected to G418 selection. Both G418-selected and non-selected cardiomyocytes were characterized by immunocytochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The teratoma-forming potential of differentiated cells was assessed by injection of about 2 million cells into the hind limb muscle of SCID mice. Results After cardiac differentiation and antibiotic selection in a suspension culture process, more than 99% of the transgenic cells showed immunoreactivity to alpha-MHC and alpha-actinin; this enrichment efficiency was observed for independent transgenic cell lines. Quantitative RT-PCR analysis revealed high levels of enrichment for cardiac-specific messages in the selected population. Importantly, injection of selected cells into six SCID mice resulted in no apparent teratoma formation, in contrast to differentiated but non-selected controls. DISCUSSION: Our results represent a significant step toward scalable production of pure human cardiomyocytes from stable, expandable hESC lines that will facilitate the development of cell therapies, safety pharmacology and drug discovery.


Assuntos
Linhagem da Célula , Células-Tronco Embrionárias , Miócitos Cardíacos , Animais , Técnicas de Cultura de Células , Diferenciação Celular , Linhagem Celular , Eletrofisiologia , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/fisiologia , Membro Posterior/patologia , Humanos , Camundongos , Camundongos SCID , Camundongos Transgênicos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/fisiologia , Transplante de Células-Tronco , Teratoma
16.
Oncogene ; 25(35): 4857-66, 2006 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-16547493

RESUMO

Paclitaxel (Taxol) is an antineoplastic agent that specifically targets microtubules and arrests cells at the G2/M phase of the cell cycle. In addition to mitotic arrest, the activation of c-Jun N-terminal kinase (JNK) signaling pathway has been demonstrated to be involved in the process leading to apoptosis. In an attempt to explore what genes are transcriptionally regulated by the activated JNK signaling pathway upon paclitaxel treatment, we used cDNA microarrays to analyse the changes of gene expression in human ovarian cancer cells that were treated with paclitaxel and/or the JNK inhibitor SP600125. Among 20 genes that were specifically regulated by the paclitaxel-activated JNK pathway, interleukin (IL)-6 was shown to elicit function through the JAK-STAT signaling pathway in an autocrine and/or paracrine fashion. Subsequently, we identified that 87.5% of eight tested ovarian cancer lines secreted detectable levels of IL-6, which could be further upregulated 2-3.2 fold by 1 microM paclitaxel. Dissection on regulatory pathways for IL-6 indicated that (i) when ovarian cancer cells were treated with paclitaxel at low but clinically achievable concentrations (exemplified by 1 microM in this study), the JNK signaling pathway was the major stimulator of IL-6 gene regulation and (ii) at suprapharmacologically high concentrations (exemplified by 50 microM), paclitaxel exerted lipopolysaccharide-like effects, most likely through the Toll-like receptor 4 signaling pathway. Collectively, these results suggest that paclitaxel upregulates functional IL-6 expression in human ovarian cancer cells through multiple signaling pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Interleucina-6/biossíntese , Interleucina-6/genética , Neoplasias Ovarianas/metabolismo , Paclitaxel/farmacologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Regulação para Cima/genética , Linhagem Celular Tumoral , Feminino , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Ovarianas/tratamento farmacológico , Fosforilação/efeitos dos fármacos , Proteínas Tirosina Quinases/fisiologia , Fatores de Transcrição STAT/fisiologia , Regulação para Cima/efeitos dos fármacos
17.
Clin Exp Allergy ; 35(7): 926-32, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16008680

RESUMO

BACKGROUND: Histo-blood groups, ABO, Lewis (Le) and secretor (Se) were found to be associated with lower lung function and wheezing in coal miners as well as in asthmatic children in some studies but not others, possibly reflecting the genetic heterogeneity among different ethnicities and local environmental exposure. OBJECTIVE: The present study was conducted to determine the association between ABO, Lewis and secretor genetic complex with susceptibility of childhood asthma in Taiwan. METHODS: We randomly selected 136 asthmatic children and 161 age-matched controls from a childhood asthma survey conducted in primary schools. ABO and Lewis blood groups were determined by red blood cell agglutination methods. Analysis of Se genotype was performed by PCR with sequence-specific primers. RESULTS: There was a higher prevalence rate in secretor subjects (Se/Se) (odds ratio (OR)=1.7, confidence interval (CI)=1.022-2.938) in asthma as compared with controls. The combined effect of these three blood systems revealed that blood group O/secretor phenotype (Se/Se) (OR=2.7, CI=1.126-6.033), and blood group O/Le(a-b-) (OR=3.6, CI=1.080-11.963, P<0.03) individuals were significantly associated with asthma. The Lewis Le(a-b-) recessive genotype (OR=3.3, CI=1.267-8.482), or the joint blood group O/Le(a-b-) phenotype (OR=5.2, CI=1.259-21.429, P<0.02), was significantly associated with high serum IgE (>500 IU), respectively. There was no association of these three blood systems with the sensitivity of dust mite, Dermatophagoide pteronyssinus, in our study population. CONCLUSIONS: We concluded that blood group O/secretors (Se/Se) and O/Le(a-b-) were associated with childhood asthma, and may act as one of the predominant factors for environmental triggers of allergy for asthmatic children in Taiwan.


Assuntos
Sistema ABO de Grupos Sanguíneos/genética , Asma/genética , Antígenos do Grupo Sanguíneo de Lewis/genética , Adolescente , Alérgenos/imunologia , Asma/epidemiologia , Asma/imunologia , Criança , Feminino , Volume Expiratório Forçado/fisiologia , Frequência do Gene/genética , Predisposição Genética para Doença/epidemiologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Imunoglobulina E/sangue , Masculino , Técnicas de Amplificação de Ácido Nucleico/métodos , Fenótipo , Reação em Cadeia da Polimerase/métodos , Prevalência , Taiwan/epidemiologia
18.
Chin J Physiol ; 46(3): 111-5, 2003 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-14672279

RESUMO

A polymorphism in the cystatin C (CST3) gene was suggested to associate with Alzheimer's disease (AD). In the present study we attempted to determine the association between CST3 polymorphism and AD or vascular dementia (VD), and whether such effects are dependent of the APOE4 allele. The polymorphisms of CST3 genotype were determined using polymerase chain reactions (PCR) followed by gel electrophoresis in 124 AD, 70 VD, and 115 control individuals. No statistical difference in CST3B allele frequencies was observed among all three groups. Associations between CST3B/B genotype and AD patients older than 75-year-old, or VD patients younger than 75-year-old were evident. The APOE4 allele alone significantly increased the odds for the developing AD, but not VD. A logistic regression analysis revealed that either CST3 or its interaction with APOE4 were not significant predictors of AD. However, a synergistic association of CST3 and APOE4 alleles was observed in predicting VD patients. These results suggest that CST3 might interact with APOE4 on conferring vascular pathologies.


Assuntos
Doença de Alzheimer/genética , Cistatinas/genética , Demência Vascular/genética , Polimorfismo Genético , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Apolipoproteína E4 , Apolipoproteínas E/genética , Cistatina C , Demência Vascular/epidemiologia , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Pessoa de Meia-Idade , Fatores de Risco
20.
Climacteric ; 5(3): 259-65, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12419084

RESUMO

OBJECTIVE: The study sought to compare the vascular resistance and serum lipids of postmenopausal women assigned to tibolone therapy or continuous combined hormone replacement therapy. DESIGN: This was a 6-month, prospective, single-blind, single-center, randomized study. A total of 50 healthy postmenopausal women were enrolled. At study end, 40 women had completed a 6-month follow-up. The first group (23 subjects) received conjugated equine estrogens (CEE) 0.625 mg/day and medroxyprogesterone acetate (MPA) 5 mg/day. The second group (17 subjects) received tibolone 2.5 mg/day. The pulsatility and resistance indexes of the carotid and middle cerebral arteries, and serum lipid profiles were monitored. RESULTS: Comparisons demonstrated that there were no significant differences between the groups in terms of changes in the pulsatility index (PI) and the resistance index (RI) of the common carotid artery (CCA), internal carotid artery (ICA), and middle cerebral artery (MCA) within the study period. Both treatments effectively reduced the total cholesterol level and with no significant differences found between the two regimens. However, in comparing the two groups, we found that high-density lipoprotein (HDL) cholesterol levels were significantly lower in the tibolone group at either 3 months or 6 months after treatment, whereas a significantly higher triglycerides level was observed in the CEE + MPA group after 3 months of treatment. Low-density lipoprotein (LDL) cholesterol levels indicated no significant differences between the two groups after treatment. CONCLUSIONS: The study demonstrated that major neck and cerebral vascular impedance was not influenced significantly by either regimen. Nonetheless, lipid profiles were affected differently by tibolone and by continuous combined CEE + MPA. However, whether or not these findings might modify cardiovascular risk is still unknown.


Assuntos
Artéria Carótida Primitiva/efeitos dos fármacos , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Artéria Cerebral Média/efeitos dos fármacos , Norpregnenos/farmacologia , Resistência Vascular/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo , Encéfalo/irrigação sanguínea , Artéria Carótida Primitiva/fisiologia , Artéria Carótida Interna/efeitos dos fármacos , Artéria Carótida Interna/fisiologia , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Circulação Coronária/efeitos dos fármacos , Esquema de Medicação , Moduladores de Receptor Estrogênico/farmacologia , Estrogênios Conjugados (USP)/administração & dosagem , Feminino , Humanos , Acetato de Medroxiprogesterona/administração & dosagem , Pessoa de Meia-Idade , Pós-Menopausa , Estudos Prospectivos , Fluxo Pulsátil/efeitos dos fármacos , Método Simples-Cego , Resultado do Tratamento , Triglicerídeos/sangue , Resistência Vascular/fisiologia
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