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1.
Clin Exp Allergy ; 48(9): 1147-1154, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29746003

RESUMO

BACKGROUND: We have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle-aged adults and in young subjects with asthma. OBJECTIVE: To investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics. METHODS: FeNO, urinary eosinophil-derived neurotoxin (U-EDN), serum eosinophil cationic protein (S-ECP) and periostin were measured in 396 asthmatics, aged 17-76 years, from the Swedish GA2LEN study. Sensitization to airborne allergens was examined with skin prick tests (≥3 mm wheal) and sensitization to food allergens with measurement of specific IgE (≥0.35 kU/L). RESULTS: Asthmatics sensitized to food allergens had higher FeNO, 22.3 ppb (18.6, 26.7) vs 16.1 ppb (14.2, 18.2) (P = .005), S-ECP, 17.7 mg/L (14.8, 21.1) vs 12.8 mg/L (10.9, 14.9) (P = .01), and periostin, 73.7 (67.5, 80.3) ng/mL vs 59.9 (55.8, 64.2) ng/mL (P = .003), than non-sensitized subjects. Periostin levels in this group were also significantly higher than in the group sensitized only to airborne allergens (P = .01). Sensitization to food allergens related independently to FeNO (P = .02), S-ECP (P = .006) and periostin (P = .004), whereas sensitization only to airborne allergens related only to FeNO (P = .02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S-ECP (r = .17, P < .001), periostin (r = .19, P < .001) and U-EDN (0.16, P < .001). S-ECP also correlated weakly with U-EDN (r = .12, P = .02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant. CONCLUSIONS & CLINICAL RELEVANCE: Sensitization to food allergens related to several local and systemic type 2 inflammation markers, such as FeNO, S-ECP and periostin. Assessing the profile of allergic sensitization, including to food allergens, might improve the understanding and interpretation of inflammatory markers and potentially improve asthma management.


Assuntos
Alérgenos/imunologia , Asma/imunologia , Asma/metabolismo , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Alimentos/efeitos adversos , Imunoglobulina E/imunologia , Adulto , Asma/diagnóstico , Biomarcadores , Testes Respiratórios , Expiração , Feminino , Hipersensibilidade Alimentar/diagnóstico , Humanos , Imunização , Masculino , Pessoa de Meia-Idade , Óxido Nítrico , Testes de Função Respiratória , Testes Cutâneos , Espirometria
2.
J Laryngol Otol ; 132(2): 111-116, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29343305

RESUMO

OBJECTIVE: This study evaluated the relationship between radiation and Eustachian tube dysfunction, and examined the radiation dose required to induce otitis media with effusion. METHODS: The function of 36 Eustachian tubes in 18 patients with head and neck cancer were examined sonotubometrically before, during, and 1, 2 and 3 months after, intensity-modulated radiotherapy. Patients with an increase of 5 dB or less in sound pressure level (dB) during swallowing were categorised as being in the dysfunction group. Additionally, radiation dose distributions were assessed in all Eustachian tubes using three dose-volume histogram parameters. RESULTS: Twenty-two of 25 normally functioning Eustachian tubes before radiotherapy (88.0 per cent) shifted to the dysfunction group after therapy. All ears that developed otitis media with effusion belonged to the dysfunction group. The radiation dose threshold evaluation revealed that ears with otitis media with effusion received significantly higher doses to the Eustachian tubes. CONCLUSION: The results indicate a relationship between radiation dose and Eustachian tube dysfunction and otitis media with effusion.


Assuntos
Tuba Auditiva/fisiopatologia , Neoplasias de Cabeça e Pescoço/radioterapia , Otite Média com Derrame/diagnóstico , Otite Média com Derrame/fisiopatologia , Radioterapia de Intensidade Modulada/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Br J Surg ; 104(11): 1549-1557, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28782798

RESUMO

BACKGROUND: Little is known about the value of portal vein (PV) resection in distal cholangiocarcinoma. The aim of this study was to evaluate the clinical significance of PV resection in distal cholangiocarcinoma. METHODS: Patients who underwent pancreatoduodenectomy (PD) for distal cholangiocarcinoma between 2001 and 2010 at one of 31 hospitals in Japan were reviewed retrospectively with special attention to PV resection. Short- and long-term outcomes were evaluated. RESULTS: In the study interval, 453 consecutive patients with distal cholangiocarcinoma underwent PD, of whom 31 (6·8 per cent) had combined PV resection. The duration of surgery (510 versus 427 min; P = 0·005) and incidence of blood transfusion (48 versus 30·7 per cent; P = 0·042) were greater in patients who had PV resection than in those who did not. Postoperative morbidity and mortality were no different in the two groups. Several indices of tumour progression, including high T classification, lymphatic invasion, perineural invasion, pancreatic invasion and lymph node metastasis, were more common in patients who had PV resection. Consequently, the incidence of R1/2 resection was higher in this group (32 versus 11·8 per cent; P = 0·004). Survival among the 31 patients with PV resection was worse than that for the 422 patients without PV resection (15 versus 42·4 per cent at 5 years; P < 0·001). Multivariable analyses revealed that age, blood loss, histological grade, perineural invasion, pancreatic invasion, lymph node metastasis and surgical margin were independent risk factors for overall survival. PV resection was not an independent risk factor. CONCLUSION: PV invasion in distal cholangiocarcinoma is associated with locally advanced disease and several negative prognostic factors. Survival for patients who have PV resection is poor even after curative resection.


Assuntos
Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/mortalidade , Colangiocarcinoma/cirurgia , Pancreaticoduodenectomia , Veia Porta/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/patologia , Perda Sanguínea Cirúrgica , Transfusão de Sangue/estatística & dados numéricos , Colangiocarcinoma/patologia , Feminino , Seguimentos , Humanos , Japão/epidemiologia , Metástase Linfática , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Duração da Cirurgia , Estudos Retrospectivos
4.
Allergy ; 72(11): 1753-1760, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28398635

RESUMO

BACKGROUND: Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear. AIM: To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics. METHODS: Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life. RESULTS: Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma. CONCLUSION: We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.


Assuntos
Asma/epidemiologia , Moléculas de Adesão Celular/sangue , Inflamação/etiologia , Pulmão/fisiopatologia , Adolescente , Adulto , Idoso , Asma/sangue , Asma/patologia , Asma/fisiopatologia , Estudos de Casos e Controles , Humanos , Pulmão/patologia , Pessoa de Meia-Idade , Rinite , Sinusite , Suécia , Adulto Jovem
5.
Br J Dermatol ; 174(6): 1327-36, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26822223

RESUMO

BACKGROUND: Squamous cell carcinoma antigen (SCCA) belongs to the ovalbumin-serpin family and is a known tumour marker. Expression of SCCA is upregulated in the serum and skin of patients with psoriasis. OBJECTIVES: The aim of this study was to determine SCCA2 levels in association with disease severity and treatment efficacy in patients with psoriasis. MATERIALS AND METHODS: Patients with psoriasis (n = 123) and healthy controls (n = 25) were enrolled in this prospective cross-sectional study. Enzyme-linked immunosorbent assay (ELISA) analysis was performed to determine serum SCCA2 levels. SCCA2 expression in skin was evaluated using immunohistochemical analysis. Serum SCCA2 levels were compared with Psoriasis Area Severity Index (PASI) scores. The effect of treatment on serum SCCA2 levels was assessed using serial examinations. Induction of SCCA2 by several psoriatic cytokines in human keratinocytes was evaluated. RESULTS: The serum levels of SCCA2 were significantly higher in patients with psoriasis than healthy controls and correlated well with disease severity. Increased SCCA2 staining was observed in lesional skin but not in nonlesional skin of patients with psoriasis. In addition, SCCA2 expression levels in skin correlated with serum concentrations of SCCA2. SCCA2 significantly decreased according to improvement of PASI scores. Interleukin (IL)-17 and IL-22 synergistically increased the production of SCCA2 at both mRNA and protein levels in human keratinocytes. CONCLUSIONS: Significant elevation of SCCA2 is associated with disease severity and reflects treatment efficacy. SCCA2 may be a useful biomarker in psoriasis, reflecting T-helper 17-type inflammation - the main determinant of the severity of psoriasis.


Assuntos
Antígenos de Neoplasias/metabolismo , Psoríase/sangue , Serpinas/metabolismo , Pele/metabolismo , Biomarcadores/metabolismo , Estudos Transversais , Fármacos Dermatológicos/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Interleucina-17/metabolismo , Interleucina-17/fisiologia , Interleucinas/metabolismo , Interleucinas/fisiologia , Queratinócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Psoríase/tratamento farmacológico , Resultado do Tratamento , Interleucina 22
6.
Br J Radiol ; 88(1053): 20150167, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26083261

RESUMO

OBJECTIVE: The purpose of this study was to evaluate plaque progression by using MRI with ultrasmall superparamagnetic iron oxide (USPIO) and by histopathological studies. METHODS: We divided 12 Watanabe heritable hyperlipidemic (WHHL) rabbits into 4 groups based on their age (3, 9, 14 and 26 months) and injected them intravenously with 0.8 mmol (Fe) kg(-1) of USPIO (size, 32 nm; concentration, 15 mg dl(-1)). On the fifth post-injection day, they were again given an intravenous injection with 40 µmol kg(-1) of the same USPIO, and MR angiography (MRA) was performed. The signal-to-noise ratio (SNR) in regions of interest in the wall of the upper abdominal aorta was calculated on coronal images. Specimens from the same level of the aorta were subjected to iron staining and RAM-11 immunostaining and used for histopathological study. For statistical analysis of the MRA and histopathological findings, we used analysis of variance [Tukey's honest significant difference (HSD) test]. RESULTS: In 9-month-old rabbits, the SNR was significantly lower than in rabbits of the other ages (p < 0.01), and the area of RAM-11 (DAKO Corporation, Glostrup, Denmark) and iron uptake in the aortic wall was significantly larger (RAM-11, p < 0.01; iron, p < 0.05). These areas were the smallest in 3-month-old rabbits. CONCLUSION: Histopathologically, the number of macrophages was the greatest in 9-month-old rabbits. Our findings indicate that the SNR on MRI scans reflects the number of macrophages in the aortic wall of WHHL rabbits. ADVANCES IN KNOWLEDGE: USPIO-enhanced MRI visualized the accumulation of macrophages in early atherosclerotic plaques of WHHL rabbits in the course of natural progression.


Assuntos
Aorta Abdominal/patologia , Aterosclerose/patologia , Hiperlipidemias/patologia , Angiografia por Ressonância Magnética/métodos , Placa Aterosclerótica/patologia , Animais , Aorta Abdominal/metabolismo , Aterosclerose/diagnóstico , Aterosclerose/metabolismo , Meios de Contraste , Dextranos , Modelos Animais de Doenças , Hiperlipidemias/diagnóstico , Hiperlipidemias/metabolismo , Macrófagos/metabolismo , Nanopartículas de Magnetita , Placa Aterosclerótica/diagnóstico , Placa Aterosclerótica/metabolismo , Coelhos
7.
Oncogenesis ; 4: e149, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-25985210

RESUMO

Sgt1/Sugt1, a cochaperone of Hsp90, is involved in several cellular activities including Cullin E3 ubiqutin ligase activity. The high level of Sgt1 expression in colorectal and gastric tumors suggests that Sgt1 is involved in tumorigenesis. Here, we report that Sgt1 is overexpressed in colon, breast and lung tumor tissues and in Ewing sarcoma and rhabdomyosarcoma xenografts. We also found that Sgt1 heterozygous knockout resulted in suppressed Hras-mediated transformation in vitro and tumor formation in p53(-/-) mouse embryonic fibroblast cells and significantly increased survival of p53(-/-) mice. Moreover, depletion of Sgt1 inhibited the growth of Ewing sarcoma and rhabdomyosarcoma cells and destabilized EWS-FLI1 and PAX3-FOXO1 oncogenic fusion proteins, respectively, which are required for cellular growth. Our results suggest that Sgt1 contributes to cancer development by stabilizing oncoproteins and that Sgt1 is a potential therapeutic target.

8.
Allergy ; 69(5): 668-73, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24673601

RESUMO

BACKGROUND: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. METHODS: In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. RESULTS: Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/µl) in the high serum periostin group. CONCLUSIONS: A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.


Assuntos
Asma/genética , Asma/fisiopatologia , Variação Genética , Receptores de Glucocorticoides/genética , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/uso terapêutico , Idoso , Asma/tratamento farmacológico , Asma/imunologia , Moléculas de Adesão Celular/sangue , Eosinófilos/imunologia , Feminino , Volume Expiratório Forçado , Estudos de Associação Genética , Proteínas de Choque Térmico/genética , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Testes de Função Respiratória , Fatores de Risco
9.
Gene Ther ; 19(12): 1141-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22189415

RESUMO

We previously demonstrated that an artificial protein, TAT-FNK, has antiapoptotic effects against cochlear hair cell (HC) damage caused by ototoxic agents when applied systemically. To examine the feasibility of topical protein therapy for inner ear disorders, we investigated whether gelatin sponge soaked with TAT-FNK and placed on the guinea pig round window membrane (RWM) could deliver the protein to the cochlea and attenuate aminoglycoside (AG)-induced cochlear damage in vivo. First, we found that the immunoreactivity of TAT-myc-FNK was distributed throughout the cochlea. The immunoreactivity was observed from 1-24 h after application. When Tat-FNK was applied 1 h before ototoxic insult (a combination of kanamycin sulfate and ethacrynic acid), auditory brainstem response threshold shifts and the extent of HC death were significantly attenuated. When cochlear organotypic cultures prepared from P5 rats were treated with kanamycin, TAT-FNK significantly reduced the extent of caspase-9 activation and HC death. These findings indicate that TAT-FNK topically applied on the RWM can enter the cochlea by diffusion and effectively prevent AG-induced apoptosis of cochlear HCs by suppressing the mitochondrial caspase-9 pathway.


Assuntos
Aminoglicosídeos/toxicidade , Apoptose/efeitos dos fármacos , Cóclea/efeitos dos fármacos , Produtos do Gene tat/farmacologia , Doenças do Labirinto/prevenção & controle , Proteínas Serina-Treonina Quinases/farmacologia , Proteínas Recombinantes de Fusão/administração & dosagem , Administração Tópica , Animais , Caspase 9/metabolismo , Cóclea/metabolismo , Ácido Etacrínico/farmacologia , Ácido Etacrínico/toxicidade , Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Produtos do Gene tat/administração & dosagem , Cobaias , Células Ciliadas Auditivas/efeitos dos fármacos , Canamicina/farmacologia , Doenças do Labirinto/induzido quimicamente , Fármacos Neuroprotetores , Proteínas Serina-Treonina Quinases/administração & dosagem , Ratos , Proteínas Recombinantes de Fusão/farmacologia , Janela da Cóclea , Proteínas Supressoras de Tumor
10.
Br J Radiol ; 84(998): 179-83, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20959369

RESUMO

OBJECTIVE: Using a liver tumour model we investigated whether thalidomide enhances the anti-tumour effect of transcatheter arterial embolisation (TAE). METHOD: First, the viability of VX2 tumour cells co-cultured with thalidomide in a 21% and 1% O(2) atmosphere was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Second, we randomly assigned 20 rabbits bearing VX2 liver tumours to 4 groups: Group 1 (thalidomide plus TAE), Group 2 (TAE only), Group 3 (thalidomide only) and Group 4 (control). Thalidomide was orally administered for 5 days. The anti-tumour effects were assessed by the tumour proliferation rate using MRI and by immunohistochemical analysis of the area of intratumoural vessels. Analysis of variance and Tukey's honestly significant difference test were used for statistical analysis. RESULTS: The viability of cells grown under hypoxic and normal conditions was not significantly different, nor was there a difference among the four groups. The tumour size increased by 55.9±29.3% in Group 1, 250.6±73.3% in Group 2, 355.2±51.7% in Group 3 and 424.7±110.7% in Group 4; the difference between Group 1 and the other three groups was significant. The area of intratumour vessels in specimens was 0.22±0.28% in Group 1, 0.42±0.29% in Group 2, 1.44±1.00% in Group 3 and 6.00±2.17% in Group 4; the difference between Group 1 and the other groups was statistically significant, as was the difference between Groups 3 and 4. CONCLUSION: Thalidomide used in combination with TAE enhanced anti-tumour effects in rabbits bearing VX2 liver tumours.


Assuntos
Antineoplásicos/uso terapêutico , Embolização Terapêutica/métodos , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Talidomida/uso terapêutico , Animais , Linhagem Celular Tumoral , Terapia Combinada/métodos , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Feminino , Gelatina/administração & dosagem , Neoplasias Hepáticas Experimentais/patologia , Microesferas , Neovascularização Patológica , Coelhos , Distribuição Aleatória , Carga Tumoral
11.
Clin Exp Allergy ; 40(8): 1266-75, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20337647

RESUMO

BACKGROUND: Tiotropium bromide, a long acting muscarinic receptor inhibitor, is a potent agent for patients with bronchial asthma as well as chronic obstructive pulmonary disease. OBJECTIVE: The aim of this study was to evaluate whether tiotropium bromide can inhibit allergen-induced acute and chronic airway inflammation, T helper (Th)2 cytokine production, and airway remodelling in a murine model of asthma. METHODS: Balb/c mice were sensitized and challenged acutely or chronically to ovalbumin (OVA). The impact of tiotropium bromide was assessed using these mice models by histologic, morphometric, and molecular techniques. Moreover, the effect of tiotropium bromide on Th2 cytokine production from purified human peripheral blood mononuclear cells (PBMCs) was assessed. RESULTS: Treatment with tiotropium bromide significantly reduced airway inflammation and the Th2 cytokine production in bronchoalveolar lavage fluid (BALF) in both acute and chronic models of asthma. The levels of TGF-beta1 were also reduced by tiotropium bromide in BALF in a chronic model. The goblet cell metaplasia, thickness of airway smooth muscle, and airway fibrosis were all significantly decreased in tiotropium bromide-treated mice. Moreover, airway hyperresponsiveness (AHR) to serotonin was significantly abrogated by tiotropium bromide in a chronic model. Th2 cytokine production from spleen cells isolated from OVA-sensitized mice was also significantly inhibited by tiotropium bromide and 4-diphenylacetoxy-N-methylpiperidine methiodide, which is a selective antagonist to the M3 receptor. Finally, treatment with tiotropium bromide inhibited the Th2 cytokine production from PBMCs. CONCLUSION: These results indicate that tiotropium bromide can inhibit Th2 cytokine production and airway inflammation, and thus may reduce airway remodelling and AHR in a murine model of asthma.


Assuntos
Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Pneumonia/tratamento farmacológico , Derivados da Escopolamina/uso terapêutico , Animais , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/biossíntese , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Pneumonia/patologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Brometo de Tiotrópio
12.
Br J Radiol ; 83(989): 428-32, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20019172

RESUMO

The aim of this study was to investigate whether the combination of cisplatin-eluting gelatin microspheres (GMSs) and flavopiridol enhances anti-tumour effects in a rabbit VX2 liver tumour model. Tumour-bearing rabbits (n = 21) were divided into five groups and infused from the proper hepatic artery. Group 1 (n = 5) received cisplatin-eluting GMSs (1 mg kg(-1)) and flavopiridol (3 mg kg(-1)), group 2 (n = 5) cisplatin-eluting GMSs alone (1 mg kg(-1)), Group 3 (n = 5) flavopiridol (3 mg kg(-1)), Group 4 (n = 3) GMSs alone (1 mg kg(-1)), and Group 5 (n = 3) was the control group receiving physiological saline (1 ml kg(-1)). On days 0 and 7 after procedures the liver tumour volume was measured using a horizontal open MRI system and the relative tumour volume growth rates for 7 days after treatment were calculated. On T(1) weighted images, the tumours were visualised as circular, low-intensity areas just below the liver surface. After treatment, the signals remained similar. The relative tumour volume growth rate for 7 days after treatment was 54.2+/-22.4% in Group 1, 134.1+/-40.1% in Group 2,166.7+/-48.1% in Group 3, 341.8+/-8.6% in Group 4 and 583.1+/-46.9% in Group 5; the growth rate was significantly lower in Group 1 than the other groups (p<0.05). We concluded that in our rabbit model of liver tumours the combination of cisplatin-eluting GMSs and flavopiridol was effective.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Flavonoides/administração & dosagem , Gelatina/administração & dosagem , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Piperidinas/administração & dosagem , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada , Imageamento por Ressonância Magnética , Microesferas , Coelhos
13.
Clin Neuropathol ; 29(1): 2-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20040326

RESUMO

OBJECTIVE: Craniopharyngioma is a benign epithelial tumor that is thought to arise from the remnant of the Rathke pouch. Malignant transformation in craniopharyngioma is extremely rare. Herein, we report a case of malignant transformation in craniopharyngioma after radiation therapy. MATERIALS AND METHODS: Histopathological and immunohistochemical analyses were carried out for specimens of the suprasellar tumor (from three resections, with the third surgery performed after radiation therapy). RESULTS: The resected tumors from the first and second surgeries comprised islands of loosely cohesive aggregates of epithelial cells, so-called stellate reticulum. At the periphery of the nests, palisaded columnar epithelium was observed. Wet keratins were scattered, and few mitotic figures were seen. The third surgical specimen was composed of irregular large nests of basaloid cells that had large, round to oval nuclei with prominent nucleoli, and mitotic figures were frequently seen (21/10 high power fields). In the center of the nests, eosinophilic ghost cells, resembling wet keratin, were observed. Accordingly, the diagnosis of malignant transformation in craniopharyngioma was made. Immunohistochemical studies revealed that the p53 protein was over-expressed in the malignant component, whereas its expression was much lower in the benign component. CONCLUSIONS: Similar to the ten previously reported cases of malignant transformation in craniopharyngioma, the present case occurred after radiation therapy. p53 protein overexpression was also observed in the earlier cases of malignant craniopharyngioma as well as in the present case (6/6 cases). We concluded that radiation therapy and p53 mutations could be involved in malignant transformation in craniopharyngioma.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/radioterapia , Craniofaringioma/patologia , Craniofaringioma/radioterapia , Neoplasias Induzidas por Radiação/patologia , Encéfalo/patologia , Encéfalo/efeitos da radiação , Encéfalo/cirurgia , Neoplasias Encefálicas/terapia , Transformação Celular Neoplásica , Criança , Craniofaringioma/terapia , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Neoplasias Induzidas por Radiação/terapia , Radioterapia/efeitos adversos
14.
Leukemia ; 24(2): 335-44, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20016539

RESUMO

We analyzed the long-term outcomes of 1021 patients with acute lymphoblastic leukemia (ALL), enrolled in four successive clinical trials (ALL811, ALL841, ALL874 and ALL911) between 1981 and 1993. All patients received risk-adopted therapy according to leukocyte count and age at the time of diagnosis. The median follow-up durations of the four studies were 17.8 years in ALL811, 15.5 years in ALL841, 11.9 years in ALL874 and 15.8 years in ALL911. Patients' event-free survival (EFS) and overall survival (OS) rates at 12 years were 41.0 and 54.3% in ALL811, 50.2 and 60.2% in ALL841, 57.3 and 64.7% in ALL874, and 63.4 and 71.7% in ALL911, respectively. Thus, cure can become a reality for about 70% of children with ALL. There is, however, still a significant difference in survival outcomes according to risk group. Late effects were observed in 70 patients out of 834 (8.4%); hepatitis and short stature were most commonly reported. Reduction of late adverse effects for all patients and development of new treatment strategies for very-high-risk patients are major issues for upcoming trials to address.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Japão , Masculino , Oncologia/organização & administração , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Prognóstico , Indução de Remissão , Fatores de Risco , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento
15.
Artigo em Inglês | MEDLINE | ID: mdl-21289047

RESUMO

Despite many decades of study, mitotic chromosomes remain poorly characterized with respect to their structure and composition. Here, we have purified mitotic chromosomes from nocodazole-treated chicken DT40 cells. These chromosomes have a 0.7:1:1 ratio of nonhistone proteins to histones to DNA. They also contain a significant content of RNAs that have yet to be characterized. Overall, the isolated chromosomes contained >4000 polypeptides, >500 of which are either novel or uncharacterized. Elsewhere, we have developed an approach for comparing the results of multiple proteomics experiments. As a validation of this approach, one of 13 novel centromere proteins identified was found to occur in a complex with the previously described proteins Ska1 and Ska2. This novel protein, now known as Ska3/Rama1, occupies a unique domain in the outer kinetochore and was revealed by RNA interference (RNAi) experiments to be essential for cell cycle progression in human cells. The approach presented here offers a powerful way to define the functional proteome of complex organelles and structures whose composition is not simple or fixed.


Assuntos
Cinetocoros/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Mitose , Proteômica/métodos , Animais , Linhagem Celular , Galinhas , DNA/metabolismo , Histonas/metabolismo , Humanos , Ligação Proteica , Proteoma/metabolismo
16.
Br J Radiol ; 82(977): 380-5, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19098080

RESUMO

The object of this study was to generate cisplatin-conjugated gelatin microspheres (GMSs) and to confirm the subsequent release of cisplatin in vitro. The GMSs (1 mg) were immersed in 50 microl of a cisplatin solution (0.06, 0.15, 0.27, 0.30 or 0.54 mg ml(-1)) at 38 degrees C to allow conjugation. The cisplatin-conjugated GMSs were then extensively washed in double-distilled water and freeze-dried. The platinum concentration in the GMSs samples was investigated as a function of the concentration of cisplatin solution used in their preparation, the number of immersions in cisplatin (1, 2, 3, 4 or 5) and the period of immersion (1, 6 or 11 h). In vitro release tests were performed at different time intervals (1, 3, 6, 12 or 24 h) to allow the rate of cisplatin release to be calculated. The platinum concentration of the GMSs increased in proportion to the concentration of cisplatin solution and the length or number of immersions in cisplatin. In vitro release tests demonstrate that the release rate (%) from GMSs after 1, 3, 6, 12 or 24 h was 4.8, 5.5, 7.6, 10.0 and 12.4, respectively. We demonstrated the ability of GMSs to bind cisplatin forming cisplatin-conjugated GMSs. Moreover, we showed that cisplatin continued to bind GMSs strongly during the in vitro release test.


Assuntos
Antineoplásicos/farmacocinética , Cisplatino/farmacocinética , Microesferas , Platina/análise , Gelatina , Humanos , Técnicas In Vitro , Fatores de Tempo
17.
Kyobu Geka ; 61(12): 1057-60, 2008 Nov.
Artigo em Japonês | MEDLINE | ID: mdl-19048908

RESUMO

We reported a case of posterior mediastinal mature teratoma. A 16-year-old woman was referred for further investigation of a left paravertebral mass detected on chest roentgenogram. The defined mass was located above the diaphragm and showed homogeneous fat density on computed tomography (CT) and hypersignal intensity on both T1 weighted images and T2 weighted images on magnetic resonance imaging (MRI). Radiologically, there was a mimicking foci of calcification. The mass was histologically diagnosed as mature teratoma.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico por imagem , Radiografia Torácica , Teratoma/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adolescente , Feminino , Humanos
18.
J Periodontal Res ; 43(6): 595-603, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18705651

RESUMO

BACKGROUND AND OBJECTIVE: The aim of this study was to identify stem cells or progenitor cells in the periodontal ligament and to investigate their behavior during wound healing of bone defects created experimentally in the alveolar process. MATERIAL AND METHODS: Intradentinal cavities were created in the mesial root of the first molar of 25 adult male rats that were killed 1, 3, 5, 7 and 14 d after surgery. At each time-point, sections were stained immunohistochemically for CD44s (standard), CD34, c-KIT, PCNA, Cbfa-1 and 5-bromo-2-deoxyuridine using primary antibodies. For morphometric analysis, the ratios of Cbfa-1 and PCNA-positive cells were calculated from the total number of positive cells/10(4) microm(2) in the cavities. RESULTS: 5-Bromo-2-deoxyuridine-positive cells were observed in the periodontal ligament and had migrated into the wound areas. A small number of CD44s-, CD34- and c-KIT-positive cells were observed in the bone marrow, but none were observed in the periodontal ligament. CD44s-positive cells were only observed in the alveolar bone cavity at 5 d after surgery. CD34- and c-KIT-positive cells were only observed in the dentin cavity at 7 d after surgery. Cbfa-1 and PCNA scores tended to show an increase 7 d after surgery. CONCLUSION: Mesenchymal stem cells and hematopoietic stem cells in the bone marrow are not involved in the regeneration of the periodontium. Cells that migrated from the residual periodontal ligament regenerated new alveolar bone at the early stage, and the regeneration around the dentin in the cavity was later than in other parts.


Assuntos
Perda do Osso Alveolar/patologia , Células-Tronco Hematopoéticas/fisiologia , Células-Tronco Mesenquimais/fisiologia , Ligamento Periodontal/citologia , Ligamento Periodontal/lesões , Regeneração/fisiologia , Animais , Regeneração Óssea/fisiologia , Diferenciação Celular , Movimento Celular , Subunidade alfa 1 de Fator de Ligação ao Core/análise , Cemento Dentário/fisiologia , Dentina/fisiologia , Técnicas Imunoenzimáticas , Masculino , Ligamento Periodontal/fisiologia , Antígeno Nuclear de Célula em Proliferação/análise , Ratos , Ratos Sprague-Dawley
19.
Kyobu Geka ; 61(7): 561-3, 2008 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-18616102

RESUMO

Sodium alginate is the main ingredient of the seaweed, and its water solution has moderate viscosity. The areas of the pleural defect and around the suture line were covered with polyglycolic acid felt by using 5% sodium alginate water solution in 41 patients who underwent pulmonary resection from November 2006 to April 2007. 28 patients were lung cancer, 6 patients were pulmonary metastasis, and 7 patients were pneumothorax. The duration of the postoperative air leakage was 0.7 days on average. Neither side effect nor complication was observed. This method is cheap, safe, and effective for prevention for postoperative pulmonary fistula.


Assuntos
Adesivos , Alginatos , Fístula/prevenção & controle , Pneumopatias/prevenção & controle , Pleura , Ácido Poliglicólico , Humanos , Neoplasias Pulmonares/cirurgia , Pneumotórax/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Soluções
20.
Kyobu Geka ; 61(6): 478-81, 2008 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-18536298

RESUMO

A 68-year-old male, pointed out of bilateral lung tumors, was hospitalized for the evaluation of multiple lung tumors. Chest computed tomography demonstrated 10 x 10 mm and 30 x 60 mm tumors in left lower lung and a 16 x 16 mm tumor in right lower lung. He was operated under the diagnosis of intracranial meningioma 26-years ago. For purpose of diagnosis, partial resections of left lower lung were performed, and then these tumors were diagnosed as pulmonary metastasis of intracranial meningioma. This is a very rare case of pulmonary metastasis of meningioma 26-years after craniotomy.


Assuntos
Craniotomia , Neoplasias Pulmonares/secundário , Neoplasias Meníngeas/patologia , Meningioma/secundário , Idoso , Diagnóstico por Imagem , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Masculino , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico , Meningioma/cirurgia , Pneumonectomia , Fatores de Tempo
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