RESUMO
The histopathologic characteristics of colorectal inflammatory polyps that formed in Miniature Dachshunds were compared with those of other colorectal proliferative lesions, including adenomas and adenocarcinomas. Fifty-three colorectal polypoid lesions were histopathologically classified into inflammatory polyps (26 cases), adenoma (18 cases), and adenocarcinoma (9 cases). All 26 dogs that were diagnosed with inflammatory polyps were Miniature Dachshunds, indicating that colorectal inflammatory polyps exhibit a marked predilection for this breed. The inflammatory polyps had complex histopathologic features and were classified into 3 stages based on their epithelial composition. In early stage (stage 1), the polyps tended to exhibit a thickened mucosa containing hyperplastic goblet cells, dilated crypts filled with a large amount of mucus, and mild lymphocyte and macrophage infiltration. In later stages (stages 2 and 3), more severe neutrophil infiltration, interstitial mucus accumulation, granulation tissue, and occasional osteoid tissue were seen. Also, a few small foci of dysplastic epithelial cells were detected. The hyperplastic goblet cells, which were a major component of the epithelium of the inflammatory polyps, were positive for cytokeratin 20 (CK20), while the dysplastic epithelial cells found in inflammatory polyps (stage 3) and the tumor cells of the adenomas and adenocarcinomas were negative for CK20. These CK20-negative epithelial cells exhibited cytoplasmic and nuclear immunoreactivity for beta-catenin. In addition, the epithelial cells in the inflammatory polyps demonstrated significantly higher cyclooxygenase 2 and fibroblast growth factor 2 expression than did those of the adenomas and adenocarcinomas, suggesting that the arachidonate cascade is involved in the development of colorectal inflammatory polyps in miniature dachshunds.
Assuntos
Adenocarcinoma/veterinária , Adenoma/veterinária , Neoplasias Colorretais/veterinária , Doenças do Cão/patologia , Hiperplasia/veterinária , Pólipos/veterinária , Adenocarcinoma/imunologia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenoma/imunologia , Adenoma/metabolismo , Adenoma/patologia , Animais , Transformação Celular Neoplásica , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Ciclo-Oxigenase 2/metabolismo , Doenças do Cão/imunologia , Doenças do Cão/metabolismo , Cães , Feminino , Hiperplasia/imunologia , Hiperplasia/metabolismo , Hiperplasia/patologia , Inflamação/imunologia , Inflamação/metabolismo , Inflamação/patologia , Inflamação/veterinária , Masculino , Pólipos/imunologia , Pólipos/metabolismo , Pólipos/patologia , beta Catenina/metabolismoRESUMO
The newly recognized ataxia-ocular apraxia 1 (AOA1; MIM 208920) is the most frequent cause of autosomal recessive ataxia in Japan and is second only to Friedreich ataxia in Portugal. It shares several neurological features with ataxia-telangiectasia, including early onset ataxia, oculomotor apraxia and cerebellar atrophy, but does not share its extraneurological features (immune deficiency, chromosomal instability and hypersensitivity to X-rays). AOA1 is also characterized by axonal motor neuropathy and the later decrease of serum albumin levels and elevation of total cholesterol. We have identified the gene causing AOA1 and the major Portuguese and Japanese mutations. This gene encodes a new, ubiquitously expressed protein that we named aprataxin. This protein is composed of three domains that share distant homology with the amino-terminal domain of polynucleotide kinase 3'- phosphatase (PNKP), with histidine-triad (HIT) proteins and with DNA-binding C2H2 zinc-finger proteins, respectively. PNKP is involved in DNA single-strand break repair (SSBR) following exposure to ionizing radiation and reactive oxygen species. Fragile-HIT proteins (FHIT) cleave diadenosine tetraphosphate, which is potentially produced during activation of the SSBR complex. The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.
Assuntos
Apraxias/genética , Ataxia/genética , Proteínas de Ligação a DNA/genética , Mutação , Proteínas Nucleares/genética , Músculos Oculomotores/fisiopatologia , Dedos de Zinco , Sequência de Aminoácidos , Apraxias/complicações , Ataxia/complicações , Sequência de Bases , Primers do DNA , Proteínas de Ligação a DNA/química , Heterozigoto , Homozigoto , Humanos , Dados de Sequência Molecular , Proteínas Nucleares/química , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de AminoácidosRESUMO
BACKGROUND: In patients with chronic renal failure undergoing haemodialysis (HD), silent cerebral infarctions (SCI) are associated with high mortality. Levels of monocyte chemoattractant protein-1 (MCP-1) increase with renal dysfunction and may be a novel predictor for cerebrovascular events. We tested the hypothesis that increased MCP-1 concentration correlate with the occurrence of SCI in HD patients. METHODS: Using cranial magnetic resonance imaging (MRI) findings, 52 Japanese patients undergoing HD were divided into two groups: with SCI (61 ± 7 years, mean ± SD, n= 28) and without SCI (60 ± 6 years, n= 24). The gender, metabolic profiles and MCP-1 concentration were compared between the two groups. RESULTS: The level of MCP-1 was higher in the with-SCI group than in the without-SCI group (P < 0.0001). The proportion of smokers was higher in the with-SCI group (P < 0.05) than in the without-SCI group. Plasma level of high-density lipoprotein cholesterol was lower, while uric acid level was higher, in the with-SCI group (P < 0.05 and P < 0.05 respectively) compared to the without-SCI group. Multiple logistic regression analysis identified MCP-1 level as being significantly associated with the presence of SCI (odds ratio 1.48, 95% confidence interval = 1.10-5.75, P < 0.0001). CONCLUSIONS: This study indicates that patients with chronic renal failure who are maintained on HD exhibit an increased prevalence of SCI, and that MCP-1 is significantly associated with the presence of SCI in HD patients.
Assuntos
Infarto Cerebral/sangue , Quimiocina CCL2/sangue , Falência Renal Crônica/complicações , Diálise Renal , Idoso , Doenças Assintomáticas , Biomarcadores , Isquemia Encefálica/sangue , Isquemia Encefálica/etiologia , Infarto Cerebral/epidemiologia , Infarto Cerebral/etiologia , Comorbidade , Feminino , Humanos , Japão/epidemiologia , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Imageamento por Ressonância Magnética , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Polimedicação , Prevalência , Estudos Prospectivos , Fatores de Risco , Fumar/epidemiologiaAssuntos
Calcitriol/análogos & derivados , Doenças do Cão/induzido quimicamente , Psoríase/tratamento farmacológico , Insuficiência Renal/induzido quimicamente , Administração Tópica , Animais , Calcitriol/administração & dosagem , Calcitriol/efeitos adversos , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Cães , Humanos , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Índice de Gravidade de DoençaRESUMO
In spite of the undisputed importance of altered expression patterns of microRNAs (miRNAs) in various cancers, there is little information on the clinicopathologic significance of cancer-related miRNAs (MIR21, MIR143, MIR144, MIR145, and MIR205) in esophageal squamous cell carcinoma (ESCC). We examined the expression levels of the precursor and mature miRNA genes in ESCC using real-time polymerase chain reaction (PCR). We also investigated the mRNA expression levels of processing elements (RNASEN, DGCR8, and DICER1) that participate in miRNA-biogenesis pathway. Furthermore, we analyzed the relationships between the expression levels of these five miRNAs and the clinicopathologic parameters of ESCC patients. The expression levels of mature MIR21 and mature MIR145 were higher in ESCC than those in normal epithelium (P < 0.05). The mature/pre ratio of MIR21 in ESCC was higher than that in normal epithelium (P < 0.05). With regard to miRNA-processing elements, the expression level of RNASEN was higher in ESCC than in normal epithelium (P < 0.05). Furthermore, altered expression of these miRNAs was related to the clinicopathologic features of ESCC patients. The high expression of mature MIR21 and mature MIR205 was associated with lymph node positivity in ESCC patients (P < 0.05). The high levels of expression of mature MIR143 and mature MIR145 were associated with recurrence of metastasis in ESCC patients (P < 0.05). The findings may imply that miRNA biogenesis is aberrantly accelerated in ESCC. Analysis of the expression levels of miRNAs should provide useful information for evaluation of the staging, prognosis, and treatment of ESCC patients.
Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND STUDY AIMS: In recent years, endoscopic submucosal dissection (ESD) has been applied for the treatment of gastric tumors, and the en-bloc resection rate of early gastric cancer has greatly improved. Herein, we introduce spring-assisted ESD, for quicker submucosal dissection. PATIENTS AND METHODS: ESD was carried out in 32 patients (20 men, 12 women; mean age 72.6 years, range 53 - 88 years) for early gastric cancer, with tumors over 10 mm in diameter. The patients were divided retrospectively into two groups (spring-assisted ESD, n = 20; conventional ESD, n = 12). To comparatively evaluate the performance speed of ESD, the circumferential length and the area of the resected specimen were calculated by the approximation formula for ellipse. Then, the circumferential cutting speed, the submucosal dissection speed, and the total ESD speed were calculated as index scores. The scores for spring-assisted ESD and conventional ESD were compared. RESULTS: The mean (+/-SD) circumferential cutting speeds in spring-assisted ESD and conventional ESD were 0.53 +/- 0.27 and 0.60 +/- 0.30 cm/minute, respectively ( P = 0.51). The mean submucosal dissection speeds in spring-assisted ESD and conventional ESD were 0.67 +/- 0.41 and 0.32 +/- 0.24 cm (2)/minute, respectively ( P = 0.005). The mean total ESD speeds in spring-assisted ESD and conventional ESD were 0.25 +/- 0.10 and 0.17 +/- 0.07 cm (2)/minute, respectively ( P = 0.015). The mean total ESD times were 57 and 75 minutes in the spring and conventional group, respectively ( P = 0.30). CONCLUSION: Using the aforementioned indices, we evaluated the performance speed of ESD. Spring-assisted ESD may allow faster submucosal dissection.
Assuntos
Dissecação/instrumentação , Dissecação/métodos , Mucosa Gástrica/cirurgia , Gastroscopia/métodos , Neoplasias Gástricas/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Gastroscópios , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Recent studies have indicated that serine phosphorylation regulates the activities of STAT1 and STAT3. However, the kinase(s) responsible and the role of serine phosphorylation in STAT function remain unresolved. In the present studies, we examined the growth factor-dependent serine phosphorylation of STAT1 and STAT3. We provide in vitro and in vivo evidence that the ERK family of mitogen-activated protein (MAP) kinases, but not JNK or p38, specifically phosphorylate STAT3 at serine 727 in response to growth factors. Evidence for additional mitogen-regulated serine phosphorylation is also provided. STAT1 is a relatively poor substrate for all MAP kinases tested both in vitro and in vivo. STAT3 serine phosphorylation, not its tyrosine phosphorylation, results in retarded mobility of the STAT3 protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Importantly, serine 727 phosphorylation negatively modulates STAT3 tyrosine phosphorylation, which is required for dimer formation, nuclear translocation, and the DNA binding activity of this transcriptional regulator. Interestingly, the cytokine interleukin-6 also stimulates STAT3 serine phosphorylation, but in contrast to growth factors, this occurs by an ERK-independent process.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Serina/metabolismo , Transativadores/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Células COS , Interleucina-6/farmacologia , MAP Quinase Quinase 1 , Fosforilação , Fator de Transcrição STAT1 , Fator de Transcrição STAT3 , Transdução de Sinais , Especificidade por Substrato , Tirosina/metabolismoRESUMO
Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.
Assuntos
Hormônio Liberador de Hormônio do Crescimento/metabolismo , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/metabolismo , Acromegalia , Adulto , Hormônio do Crescimento Humano/sangue , Humanos , Hiperplasia , Hipertireoidismo/complicações , Hipertireoidismo/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Imageamento por Ressonância Magnética , Masculino , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico por imagem , Neoplasia Endócrina Múltipla Tipo 1/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Doenças da Hipófise/patologia , Tomografia Computadorizada por Raios XRESUMO
Sodium nitrate was given to male noninbred Wistar rats at levels of 800 ppm and 1,600 ppm in a pellet diet for 646 experimental days. The first tum or was found on day 441 in the liver of a rat given a diet containing 800 ppm sodium nitrite. On day 646, liver tumors were found in 1 of 22 rats (4.5%) on an 800-ppm sodium nitrite diet and in 5 of 19 rats (26.3%) on a 1,600-ppm sodium nitrite diet. The incidence of liver tumors in the rats fed 1,600 ppm sodium nitrite was significantly different from that in controls as judged by the t-test (P < 0.05). A hepatocellular carcinoma and a hemangioendothelial sarcoma of the liver were found on day 646 in 2 rats fed 1,600 ppm sodium nitrite. One mammary tumor but no liver tumors were found in the 19 control rats. The concentration of sodium nitrite decreased after preparation of the pellet diet, but it was still at least 70% of the initial amount when the pellets were given to the rats. Volatile N-nitroso compounds, especially dimehylnitrosamine, at ppm levels were detected in the pellet diet with a gas chromatography-thermal energy analyzer.
Assuntos
Carcinógenos , Neoplasias Hepáticas/induzido quimicamente , Nitritos/toxicidade , Nitrito de Sódio/toxicidade , Adenoma/induzido quimicamente , Animais , Carcinoma/induzido quimicamente , Carcinoma/patologia , Dieta , Relação Dose-Resposta a Droga , Hemangiossarcoma/induzido quimicamente , Hemangiossarcoma/patologia , Neoplasias Hepáticas/patologia , Masculino , Neoplasias Experimentais/induzido quimicamente , Compostos Nitrosos/toxicidade , Ratos , Fatores de TempoRESUMO
The carcinogenicity of the pyrrolizidine alkaloids senkirkine and symphytine was studied in male inbred ACI rats. Animals were divided into 3 groups: Group I received ip injections of freshly prepared senkirkine at a dose of 10% of the median lethal dose (LD50) twice weekly for 4 weeks and then once a week for 52 weeks. Group II received ip injections of symphytine at a dose of 10% of the LD50 by the same injection schedule as in group I. The control group was given ip injections of a 0.9% NaCl solution following the same injection schedule as in experimental groups. All group I rats survived for more than 290 days after the start of injections, and 9 of 20 rats developed liver cell adenoma. All group II animals survived for more than 330 days after the start of injections. Of 20 rats, 4 had liver tumors, 3 had hemangioendothelial sarcomas, and 1 had liver cell adenoma. The hemangioendothelial sarcomas showed metastasis in the lungs of 2 rats. The control group had no liver tumors.
Assuntos
Neoplasias Hepáticas/induzido quimicamente , Alcaloides de Pirrolizidina/toxicidade , Animais , Hemangioendotelioma/induzido quimicamente , Hemangioendotelioma/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Neoplasias Experimentais/induzido quimicamente , Ratos , Ratos Endogâmicos ACI , Fatores de TempoRESUMO
The serum levels of CA 19-9 and DU-PAN-2 antigens and their expression in tumor tissue were examined in 22 pancreatic cancer patients and the results were correlated with the Lewis (Le) blood group phenotypes of the individuals. In tumor tissue, CA 19-9 was expressed in 17 of 22 (77%) specimens. The negative cases included three patients with Lea-b-, one with Lea+b- and the other with Lea-b+ phenotypes. DU-PAN-2 antigen was expressed in 20 of 22 (91%) cancer tissues. The two DU-PAN-2-negative cases were CA 19-9-positive. The combination of two markers increased the sensitivity to 100%. In the serum, CA 19-9 level was elevated (greater than 37 U/ml) in 16 of 21 (73%) cases. All Lea-b- patients had values less than 37 U/ml. An elevated level of DU-PAN-2 (greater than 300 U/ml) was detected in 14 of 21 (67%) patients including three cases with Lea-b- type. In only one patient were both antigens below the cutoff levels so that the combination of two biomarkers elevated the sensitivity to 95%. The study indicated that the cocktail of 19-9 and DU-PAN-2 antibodies might increase the sensitivity and specificity for clinical diagnosis of pancreatic cancer. In 19 of 21 (90%) cases, the serum CA 19-9 level correlated with the expression of the antigen in the cancer tissue. Discrepancy was seen in two cases; one patient had an elevated level of CA 19-9 in the serum, but lacked this antigen in the cancer cells. In the second case, the situation was reversed. For DU-PAN-2, positive correlation was seen in 14 of 21 (67%) cases. Six of seven patients with low DU-PAN-2 levels expressed the antigen in their tumor cells, and one patient with DU-PAN-2-negative cancer tissue had an elevated level of this marker in the serum. Thus, CA 19-9 expression in serum corresponded more closely to expression in tissue than did that of DU-PAN-2 antigen. The serum levels of these antigens, however, is likely due to multiple factors, only one of which is the qualitative and quantitative expression of the antigens in tumors.
Assuntos
Antígenos de Neoplasias/análise , Neoplasias Pancreáticas/imunologia , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-IdadeRESUMO
Blood group A, B, H, Le, Leb, Lex, and Ley antigenicity as well as the expression of CA 19-9 were examined in pancreatic cancer specimens from 30 patients, using monoclonal antibodies to the respective antigen and immunohistochemical techniques, and the findings were correlated with the blood group types (ABO and Lewis) of the individuals. Compatible antigen expression was found in 82, 75, and 50% of tumors from patients with A, B, and O blood group types, respectively. Deletion of the compatible antigen was found in 10 (33%) of the cases, predominantly in patients of blood group O type, and incompatible expression (of B antigen only) in 4 (13%). Lea was detected in 87%, Leb in 90%, Lex in 30%, and Ley in 43% of the specimens, regardless of ABH and Lewis phenotype of the patients. Coexpression of Lea and Leb was found in 87%, of Lex and Ley in 13%, of Lea and Lex in 23%, and of Leb and Ley in 40% of the cases. CA 19-9 was expressed in 80% of the tumors; it was present in the tumor tissue of 21 of 22 patients from Lea-b+, in all 4 individuals from Lea+b-, but in none of the 4 patients from Lea-b- phenotype (P less than 0.01). Heterogeneity in the expression of each of the antigens was found. The overall results indicate that blood group antigen expression in pancreatic tumor differs from that of other gastrointestinal cancers and that the Lewis antigen expression in pancreatic cancer cells is independent of the blood group phenotype of the patients and thus may be useful as a tumor marker.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Antígenos de Neoplasias/imunologia , Tipagem e Reações Cruzadas Sanguíneas , Antígenos do Grupo Sanguíneo de Lewis/imunologia , Neoplasias Pancreáticas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Glicosídicos Associados a Tumores , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/imunologia , FenótipoRESUMO
Carbohydrate antigen (CA) 19-9 identified by a murine monoclonal antibody against a colorectal carcinoma antigen is thought to be a sialylated Lewis (Le)a blood group antigen and occurs in high concentration in serum of patients with pancreatic carcinoma. This study was designed to identify the relationship between Lewis antigens and CA 19-9 in patients with pancreatic cancer. The following analyses were performed in 20 pancreatic cancer patients: Lea and Leb antigen phenotype in saliva (modified enzyme-linked immunosorbent assay) or on red cells (hemagglutination); CA 19-9 levels (radioimmunoassay) in serum; and CA 19-9 and Lea and Leb expression (immunoperoxidase assay) on tumor tissue. Lea-b- patients based on salivary phenotype failed to express CA 19-9 in tumor tissue and had normal or low levels of CA 19-9 (less than 37 units/ml) in serum (P = 0.0011, versus Lea+b- and Lea-b+ patients). Eighty-eight % of Lea+b- and Lea-b+ patients had elevated serum CA 19-9 levels (greater than 37 units/ml). All Lea+b- and Lea-b+ patients expressed both Lea and Leb antigens in tumor tissue. These results support the view that Lea-b- pancreatic cancer patients cannot manufacture CA 19-9. Surprisingly, Lea-positive patients express Leb antigen in tumor tissue; in this subgroup, Leb antigen may be a tumor-specific biomarker.
Assuntos
Antígenos de Neoplasias/análise , Antígenos do Grupo Sanguíneo de Lewis/análise , Neoplasias Pancreáticas/análise , Adenocarcinoma/análise , Anticorpos Monoclonais , Antígenos Glicosídicos Associados a Tumores , Biomarcadores Tumorais/análise , Humanos , Técnicas Imunoenzimáticas , Imuno-Histoquímica , Fenótipo , Radioimunoensaio , Saliva/análiseRESUMO
Acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) are mitogenic polypeptides that may contribute to cancer cell proliferation. In the present study we examined aFGF and bFGF expression in human pancreatic cancer. Northern blot analysis of total RNA isolated from 12 pancreatic cancers revealed elevated aFGF and bFGF mRNA levels in 12 and 10 samples, respectively, by comparison with the normal human pancreas. Immunostaining demonstrated the presence of aFGF and bFGF in many cancer cells and in the atrophic acini and ducts adjacent to the cancer cells, but to a much lesser extent in the surrounding fibroblasts. By in situ hybridization, both mRNA moieties colocalized with their respective proteins and were abundant in many cancer cells. Immunoblotting confirmed that cancer tissues with increased aFGF and bFGF immunoreactivity contained elevated levels of both proteins. To determine the significance of aFGF and bFGF expression in the pancreatic cancer cells, immunohistochemical analysis of 78 human pancreatic carcinomas was performed. aFGF and bFGF immunoreactivity was present in the cancer cells in 47 (60%) and 44 (56%) of the tumors, respectively. There was a significant correlation between the presence of either aFGF or bFGF in the cancer cells and advanced tumor stage, and the presence of bFGF and shorter patient survival. These data suggest that aFGF and bFGF are overexpressed in a significant proportion of human pancreatic carcinoma cells and that this overexpression may contribute to disease progression.
Assuntos
Fator 1 de Crescimento de Fibroblastos/biossíntese , Fator 2 de Crescimento de Fibroblastos/biossíntese , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/análise , Northern Blotting , Sondas de DNA , Feminino , Fator 1 de Crescimento de Fibroblastos/análise , Fator 2 de Crescimento de Fibroblastos/análise , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pâncreas/citologia , Pâncreas/patologia , Neoplasias Pancreáticas/mortalidade , Sondas RNA , RNA Mensageiro/análise , RNA Neoplásico/análise , Análise de SobrevidaRESUMO
INTRODUCTION: Although hepatic vein stenosis after liver transplantation is a rare complication, the complication rate of 1% to 6% is higher in pediatric living-donor liver transplantation than that in other liver transplantation cases. Diagnosis is very important because this complication can cause hepatic congestion that develops to liver cirrhosis, graft loss, and patient loss. However, this is unlikely in cases where there are no ascites or hypoalbuminemia. OBJECTIVES: Eleven of 167 patients who had undergone pediatric living-donor liver transplantation were identified in the outpatient clinic at Jichi Medical University as having suffered from hepatic vein stenosis, and were enrolled in the study. METHODS: We conducted a retrospective study in which we reviewed historical patient records to investigate the parameters for diagnosis and examine treatment methods and outcomes. RESULTS: The 11 patients were treated with 16 episodes of balloon dilatation. Three among these received retransplantation and another 2 cases required the placement of a metallic stent at the stenosis. Histological examination revealed severe fibrosis in four of nine patients who had a liver biopsy, with mild fibrosis revealed in the other five grafts. Furthermore, hepatomegaly and splenomegaly diagnosed by computed tomography, elevated levels of hyarulonic acid, and/or a decrease in calcineurin inhibitor clearance were found to be pathognomonic at diagnosis, and tended to improve after treatment. CONCLUSIONS: Diagnosis of hepatic vein stenosis after liver transplantation can be difficult, so careful observation is crucial to avoid the risk of acute liver dysfunction. Comprehensive assessment using volumetry of the liver and spleen and monitoring of hyarulonic acid levels and/or calcineurin inhibitor clearance, in addition to some form of imaging examination, is important for diagnosis and evaluation of the effectiveness of therapy.
Assuntos
Algoritmos , Veias Hepáticas/diagnóstico por imagem , Hepatomegalia/diagnóstico por imagem , Transplante de Fígado , Complicações Pós-Operatórias/diagnóstico por imagem , Esplenomegalia/diagnóstico por imagem , Adolescente , Inibidores de Calcineurina/metabolismo , Cateterismo , Criança , Pré-Escolar , Constrição Patológica/sangue , Constrição Patológica/complicações , Constrição Patológica/diagnóstico por imagem , Dilatação , Feminino , Hepatomegalia/complicações , Humanos , Ácido Hialurônico/sangue , Lactente , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Doadores Vivos , Masculino , Complicações Pós-Operatórias/sangue , Reoperação , Estudos Retrospectivos , Esplenomegalia/complicações , Stents , Tomografia Computadorizada por Raios X , Ultrassonografia DopplerRESUMO
One of the hurdles to adenovirus (Ad)-mediated gene transfer is that Ad vectors mediate inefficient gene transfer into cells lacking in the primary receptors, Coxsackievirus and adenovirus receptor (CAR). We previously developed a fiber-mutant Ad vector containing the Arg-Gly-Asp (RGD)-containing peptide motif on the HI loop of the fiber knob, and showed that the mutant vector had enhanced gene transfer activity to human glioma cells, which showed little CAR expression, compared to the vector containing wild type fiber. In this study, the feasibility of the Ad vector containing RGD peptide on the fiber knob was examined in a wide variety of cell types: CAR-positive or -negative human tumor cells, mouse cells, and leukemia cells. The mutant vector infected the cells, which lacked CAR expression but showed alpha(v) integrin expression, about 10-1000 times more efficiently than the vector containing wild type fiber via an RGD-integrin (alpha(v)beta3 and alpha(v)beta5)-dependent, CAR-independent cell entry pathway. The results of this study indicate that Ad vector containing RGD peptide on the fiber knob could be of great utility for gene therapy and gene transfer experiments.
Assuntos
Adenoviridae/genética , Técnicas de Transferência de Genes , Oligopeptídeos/genética , Animais , Linhagem Celular , Terapia Genética , Vetores Genéticos , Humanos , Integrinas/análise , Camundongos , Receptores Virais/análise , Receptores de Vitronectina/análise , Células Tumorais CultivadasRESUMO
Fusogenic liposome, a unique vector prepared by fusing ultraviolet-inactivated Sendai virus and liposome, is known to efficiently deliver content into various animal cells through membrane fusion. In this study, we examined the target-cell specificity of fusogenic liposome (FL)-mediated macromolecule delivery into human blood cells using diphtheria toxin fragment A (DTA) as a probe. Among the peripheral blood mononuclear cells (PBMC), FL was able to deliver its encapsulates into CD14+ monocytes and CD4-/CD8- T-cells, but not into CD19+ B-lymphocytes, CD4+ T-cells or CD8+ T-cells. The susceptibility of human leukemia cell lines to FL was similar to that of PBMC; the order of the reactivity was U937 (monoblastic leukemia)>MOLT4, Jurkat (T-lymphoma)>Daudi, BALL1 (B-lymphoma)>K562 (erythroblastic leukemia). Interestingly, FL showed similar binding activity to all of these leukemia cell lines. These findings indicate that, among blood cells, monocytes, monoblastic leukemia cells, CD4-/CD8- T-cells and T-lymphoma cells are preferable targets for FL-mediated macromolecule delivery. This is the first demonstration of the existence of non-permissive cells against FL. Our results also suggest that some molecules on target-cells other than the binding targets of SV-derived protein may participate in fusion between FL and cells.
Assuntos
Membranas Intracelulares/fisiologia , Fusão de Membrana , Monócitos/fisiologia , Toxina Diftérica/farmacologia , Portadores de Fármacos , Células HeLa , Humanos , Lipossomos , Monócitos/ultraestrutura , Fragmentos de Peptídeos/farmacologia , Respirovirus/fisiologia , Linfócitos T , Células Tumorais Cultivadas , Proteínas Virais/fisiologiaRESUMO
Neuroendocrine (NE) carcinoma was diagnosed in 10 dogs. In six cases examined by cephalometric radiography and computerized tomography, a large mass was seen to fill the nasal cavity. Histopathologically, sheets, nests or ribbons of neoplastic cells were separated by delicate or thick fibrovascular stroma. The neoplastic cells were round, oval, or spindle-shaped; cytoplasmic granules and hyperchromatic nuclei with prominent nucleoli were present. Neoplastic cells were invariably immunohistochemically positive for cytokeratin (CK) AE1/AE3, neuron-specific enolase, chromogranin A and vasoactive intestinal polypeptide. Eight dogs were positive for S100 protein, seven for synaptophysin, five for protein gene product 9.5, two for somatostatin, and one for Leu-7. Immunolabelling gave negative results for CK 8, CK 19, calcitonin, calcitonin gene-related polypeptide, neurofilaments, serotonin, gastrin and glial fibrillary acidic protein. Ultrastructurally, the neoplastic cells contained a large number of round, membrane-bounded, densely-cored granules corresponding to neurosecretory granules. These observations were consistent with the neuroendocrine nature of the carcinomas.
Assuntos
Carcinoma Neuroendócrino/veterinária , Doenças do Cão/patologia , Cavidade Nasal/patologia , Neoplasias Nasais/veterinária , Animais , Biomarcadores Tumorais/análise , Carcinoma Neuroendócrino/química , Carcinoma Neuroendócrino/patologia , Grânulos Citoplasmáticos/ultraestrutura , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/mortalidade , Cães , Feminino , Técnicas Imunoenzimáticas/veterinária , Masculino , Microscopia Eletrônica de Transmissão/veterinária , Cavidade Nasal/diagnóstico por imagem , Sistemas Neurossecretores/ultraestrutura , Neoplasias Nasais/química , Neoplasias Nasais/patologia , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/veterináriaRESUMO
BACKGROUND: The association of diverticula with bowel habits is unclear. We therefore analyzed the association between diverticula and bowel habits in over 1000 Japanese individuals. METHODS: Japanese subjects who underwent total colonoscopies at seven centers in Japan from June to September 2013 were analyzed. Bowel habits were evaluated using the Gastrointestinal Symptom Rating Scale, and stool form was assessed using a part of the Bristol Scale and Rome ΙΙΙ criteria. Diverticula were diagnosed by colonoscopy with a transparent soft-short hood. KEY RESULTS: The study evaluated 1066 subjects, 648 males and 418 females (ratio, 1.55 : 1), of mean age 63.9 ± 13.0 years. After adjusting for age and sex, the presence of constipation was associated with a significantly reduced likelihood of diverticula (odds ratio [OR] = 0.70, 95% confidence interval [CI] 0.52-0.93). When assessed according to the location of diverticula, the presence of constipation was associated with a significantly decreased likelihood of left-sided (OR = 0.39, 95% CI 0.16-0.93), but not right-sided (OR = 1.10, 95% CI 0.48-2.53), diverticula. Furthermore, stool form was unrelated with the presence or absence of diverticula. CONCLUSIONS & INFERENCES: The wide-spread hypothesis that constipation was associated with colonic diverticula was not supported. Rather, we found that the absence of diverticula was associated with constipation, suggesting the need to reassess the etiology of colonic diverticula.