Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 98
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Anticancer Res ; 40(1): 293-298, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892579

RESUMO

BACKGROUND/AIM: The prognosis of pancreatic cancer remains poor with a high incidence of recurrence even after curative resection. The aim of this study was to investigate prognostic factors in patients with recurrent pancreatic cancer using the multicenter database. PATIENTS AND METHODS: The subjects were 196 patients with recurrent pancreatic cancer who underwent resection between 2008 and 2015. We retrospectively investigated the relation between clinicopathological characteristics of the patients and overall survival from recurrence using univariate and multivariate analyses. RESULTS: In univariate analysis, the positive lymphatic invasion (p=0.0240), time to recurrence from resection <1 year (p<0.0001), sites of recurrence except for local or lymph node (p=0.0273), liver recurrence (p=0.0389) and peritoneal recurrence (p<0.0001) were significantly associated with poor overall survival from recurrence. In multivariate analysis, time to recurrence from resection <1 year (p<0.0001) and peritoneal recurrence (p<0.0001) were independently associated with poor overall survival from recurrence. CONCLUSION: Time to recurrence from resection <1 year and peritoneal recurrence were significant independent predictors of poor overall survival from recurrence in patients with recurrent pancreatic cancer.


Assuntos
Recidiva Local de Neoplasia/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Peritoneais/patologia , Prognóstico
2.
Anticancer Res ; 39(11): 6325-6332, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31704863

RESUMO

BACKGROUND/AIM: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older. PATIENTS AND METHODS: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or older; n=16). RESULTS: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence. CONCLUSION: Hepatic resection for HCC and CRLM in patients aged 80 years and older may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and older, hepatic resection may be effective when negative surgical margins can be achieved.


Assuntos
Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Comorbidade , Intervalo Livre de Doença , Feminino , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Masculino , Margens de Excisão , Complicações Pós-Operatórias , Análise de Sobrevida , Resultado do Tratamento
3.
Anticancer Res ; 39(9): 5143-5148, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519626

RESUMO

BACKGROUND/AIM: We aimed to assess surgical outcome and long-term survival after elective hepatic resection for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM) in patients aged 80 years or older. PATIENTS AND METHODS: This study included 100 patients aged 70 years or older, who underwent hepatic resection for HCC or CRLM between January 2000 and December 2012. Outcomes and clinicopathological data were compared between the elderly (aged 70-79 years; n=84) and extremely elderly groups (aged 80 years or over; n=16). RESULTS: Incidence of postoperative complications, in-hospital mortality, and postoperative OS in the extremely elderly group were comparable with those of the elderly group. In patients with HCC, the extremely elderly group was associated with shorter DFS (p=0.030) in univariate analysis, while multivariate analysis showed significant and independent factors of cancer recurrence. CONCLUSION: Hepatic resection for HCC and CRLM in patients aged 80 years and over may be safe and acceptable with appropriate selection. For HCC in patients aged 80 years and over, hepatic resection may be effective when negative surgical margins can be achieved.


Assuntos
Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Resultado do Tratamento
4.
Endocrinol Diabetes Metab ; 2(3): e00068, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31294084

RESUMO

The rapid rise in the prevalence of type 2 diabetes mellitus (T2DM) poses a huge healthcare burden across the world. Although there are several antihyperglycaemic agents (AHAs) available including addition of new drug classes to the treatment algorithm, more than 50% of patients with T2DM do not achieve glycaemic targets, suggesting an urgent need for treatment strategies focusing on prevention and progression of T2DM and its long-term complications. Lifestyle changes including implementation of healthy diet and physical activity are cornerstones for the management of T2DM. The positive effects of diet and exercise on incretin hormones such as glucagon-like peptide-1 (GLP-1) have been reported. We hypothesize an IDEP concept (Interaction between Diet/Exercise and Pharmacotherapy) aimed at modifying the diet and lifestyle, along with pharmacotherapy to enhance the GLP-1 levels, would result in good glycaemic control in patients with T2DM. Consuming protein-rich food, avoiding saturated fatty acids and making small changes in eating habits such as eating slowly with longer mastication time can have a positive impact on the GLP-1 secretion and insulin levels. Further the type of physical activity (aerobic/resistance training), intensity of exercise, duration, time and frequency of exercise have shown to improve GLP-1 levels. Apart from AHAs, a few antihypertensive drugs and lipid-lowering drugs have also shown to increase endogenous GLP-1 levels, however, due to quick degradation of GLP-1 by dipeptidyl peptidase-4 (DPP-4) enzyme, treatment with DPP-4 inhibitors would protect GLP-1 from degradation and prolong its activity. Thus, IDEP concept can be a promising treatment strategy, which positively influences the GLP-1 levels and provide additive benefits in terms of improving metabolic parameters in patients with T2DM and slowing the progression of T2DM and its associated complications.

5.
J Gastrointest Surg ; 2019 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31062271

RESUMO

AIMS: The benefit of preoperative biliary drainage for patients with operable periampullary cancers is controversial because biliary drainage would activate inflammatory response such as cholangitis. The aim of this study was to identify a novel prognostic score in patients with operable periampullary cancers including pancreatic cancer and extrahepatic distal bile duct cancer with a typical reference to preoperative biliary drainage and inflammatory status. METHODS: Between 2000 and 2015, 246 patients were enrolled in this retrospective study. The patients were divided into four groups of the following three factors; the presence of preoperative biliary drainage, decreased serum albumin value (< 3.5 g dl-1), and increased CR P value (> 1.0 mg dl-1). The relationship between clinicopathological variables and disease-free survival (DFS) as well as over-all survival (OS) was investigated by univariate and multivariate analyses. To compare the sensitivity and specificity among the types of cancer, the area under the receiver operating characteristics curve (AUC) was evaluated in patients with pancreatic cancer and extrahepatic distal bile duct cancer. RESULTS: In multivariate analysis of DFS and OS, the novel prognostic factor combining preoperative biliary drainage and inflammatory status was an independent risk factor of tumor recurrence and prognosis as well as differentiation of the tumor and resected margin. CONCLUSION: The novel prognostic score combining preoperative biliary drainage and inflammatory status may be an independent predictor of tumor recurrence and prognosis in patients with periampullary cancers.

6.
Acta Med Okayama ; 73(2): 161-171, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31015751

RESUMO

Second allogeneic stem cell transplantation (allo-SCT) is a potentially curative therapy for patients who relapse after first allo-SCT. Human leukocyte antigen (HLA)-haploidentical related donors provide the broad opportunity to conduct second SCT at the appropriate time, but the efficacy of second SCT from haploidentical donors after relapse has not been established. We retrospectively analyzed the records of 33 patients who underwent second SCT. Twenty patients underwent haplo-SCT with low-dose antithymocyte globulin (ATG), and the other 13 patients underwent conventional- SCTs, including HLA-matched related peripheral blood, unrelated bone marrow or cord blood. Three years after the second SCT, the overall survival (OS) and progression-free survival (PFS) of all patients were 32.5% and 23.9%. Multivariate analyses indicated that non-complete response at second SCT, less than 1-year interval to relapse after first- SCT, and total score ≥ 3 on the hematopoietic cell transplantation-specific comorbidity index were significantly associated with a lower PFS rate. The haplo- and conventional- SCT groups showed equivalent results regarding OS, PFS, cumulative incidences of relapse, non-relapse mortality and graft-versus-host disease. The neutropenic period after transplantation was significantly shorter in haplo- SCT than conventional- SCT (10.5 days vs. 16 days, p=0.001). Our analysis revealed that haplo-SCT could be an alternative therapeutic option for relapsed patients after first SCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/genética , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
7.
Anticancer Res ; 39(3): 1469-1478, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842184

RESUMO

BACKGROUND/AIM: Prediction of local recurrence and distant metastasis is important for patients with pancreatic cancer following pancreatic resection. The aims of this study were to identify a novel prognostic score which combines distance from common hepatic artery (CHA) or superior mesenteric artery (SMA) and examine serum CA19-9 for predicting local recurrence in patients with pancreatic cancer following resection. PATIENTS AND METHODS: This retrospective study comprised 149 patients who went through elective pancreatic resection for pancreatic cancer between June 2007 and December, 2017. We established new scores (CHA score and SMA score) using the distance between CHA or SMA and the tumor measured by preoperative CT scan in combination with preoperative serum CA19-9 values. We evaluated the relationship between the scores and local recurrence of pancreatic cancer. Finally, we investigated the relationship between the scores and local recurrence-free survival as well as the overall survival. RESULTS: The optimal cut-off levels of the distance between CHA or SMA and the tumor, as determined by ROC analysis, were 20.55 and 10.9 mm, respectively. In a logistic progression model, demonstrated by multivariate analysis, lymphatic invasion (p=0.002), preoperative serum CA19-9 (p=0.007) and SMA score (p=0.004) were identified to be independent predictors of local recurrence in patients with pancreatic cancer following resection. In a Cox progression model, demonstrated by multivariate analysis, intraoperative blood loss (p=0.022), lymphatic invasion (p=0.001) and SMA score (p<0.001) were identified as independent factors of local recurrence. The independent predictors of poor overall survival by multivariate analysis consisted of intraoperative blood loss (p=0.045), intraoperative transfusion (p=0.026) and SMA score (p<0.001). CONCLUSION: The SMA score may be an independent preoperative predictor of local recurrence and prognosis in patients with pancreatic cancer.


Assuntos
Antígeno CA-19-9/sangue , Artéria Mesentérica Superior/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Neoplasias Pancreáticas , Idoso , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Prognóstico , Tomografia Computadorizada por Raios X , Ultrassonografia
8.
J Surg Res ; 238: 102-112, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30769246

RESUMO

BACKGROUND: Inflammation-based prognostic scores are associated with tumor recurrence and survival in various cancers. The aim of this study was to identify the significance of inflammation-based prognostic scores and to detect the most useful score in patients with distal extrahepatic bile duct cancer after pancreaticoduodenectomy. METHODS: Between 2000 and 2015, 121 patients were enrolled in this retrospective study. The relationship between clinicopathological variables including various prognostic scores and disease-free (DFS) as well as overall (OS) survival was investigated by univariate analysis. The area under the receiver operating characteristics curve was calculated to compare the predictive ability of each scoring system. Multivariate analysis was performed to identify the clinicopathological variables associated. RESULTS: In univariate analysis, Glasgow prognostic score (GPS), mGPS, C-reactive protein/Alb ratio score, prognostic index, and preoperative monocyte count were significant risk factors for both DFS and OS. The area under the receiver operating characteristics curve of GPS is consistently larger in comparison with other four scores in both DFS as well as OS. In multivariate analysis, GPS was an independent risk factor of both tumor recurrence and poor prognosis. CONCLUSIONS: GPS score is an independent tumor recurrence and prognostic factor in patients with distal extrahepatic bile duct cancer and is superior to the other prognostic scores.

9.
Oncoimmunology ; 8(2): e1538440, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30713797

RESUMO

The CD28H/B7-H5 pathway is a newly identified pathway of the B7 family. In human peripheral blood, the receptor CD28H is preferentially expressed on naïve T cells and repetitive stimulation of T cells leads to the loss of CD28H expression. Here we examined the expression of the CD28H/B7-H5 pathway in human peripheral tissues, as well as in human cancers. We found that CD28H is preferentially expressed on T cells with tissue-resident phenotypes (TRM). Supporting that, stimulation via IL-15 and TGF-ß, presumably major cytokines essential for TRM cell homeostasis, sustains CD28H expression on T cells. The ligand B7-H5 is constitutively expressed on normal epithelium of human oral-gastrointestinal tracts. In human cancers, CD28H is preferentially present on tumor infiltrating lymphocytes (TILs) with TRM features and identifies a TRM subset with less cytotoxicity. Taken together, our studies suggest that the CD28H/B7-H5 pathway involves the interactions between TRM cells and epithelium, and could be important for human TRM homeostasis and function.

10.
Anticancer Res ; 38(11): 6491-6499, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30396977

RESUMO

AIM: Prognostic factors of recurrence and survival in various cancer types have been reported and include C-reactive protein (CRP)-based measures as evidenced by the Glasgow prognostic score (GPS), as well as peripheral blood cell-based prognostic values such as the prognostic index (PI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). The aim of this study was to identify significant prognostic values and compare them for suitability for use in patients after curative pancreatic resection for pancreatic cancer. MATERIALS AND METHODS: Between 2000 and 2015, 188 patients were enrolled in this retrospective study. The relationship between clinicopathological variables including various prognostic values and disease-free (DFS) and overall (OS) survival was investigated by univariate analysis. The area under the receiver operating characteristics curve (AUC) was evaluated to compare the predictive ability of each of these scoring systems. Multivariate analysis was then performed to identify clinicopathological variables that associated DFS and OS. RESULTS: In univariate analysis, GPS, modified GPS, CRP to albumin ratio and PI were significant risk factors for both DFS and OS. The AUC of CRP-based scores (GPS, modified GPS, and CRP to albumin ratio) were consistently larger in comparison with PI, which consists of both CRP and peripheral blood cell scores, at all time points for both DFS and OS. In multivariate analysis, GPS was the only independent risk factor of tumor recurrence and survival. CONCLUSION: CRP-based prognostic scores have an independent value for both tumor recurrence and prognosis in patients after curative resection for pancreatic cancer, and are superior to other peripheral blood cell count-based prognostic scores.


Assuntos
Proteína C-Reativa/metabolismo , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Contagem de Células Sanguíneas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Prognóstico , Análise de Sobrevida , Resultado do Tratamento
11.
Cancer Res ; 78(23): 6655-6665, 2018 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30315115

RESUMO

: Thalidomide-like drugs have been approved for the treatment of human multiple myeloma, with their direct antitumor effects and immunomodulatory functions well documented. However, the exact molecular mechanisms that govern these effects remain unclear. Here we demonstrate that pomalidomide promotes immune response by inhibiting expression of PD-L1. Pomalidomide inhibited PD-L1 expression on tumor cells to promote CTL activity in vitro and suppressed PD-L1 upregulation on antigen-presenting cells to prevent peptide-induced T-cell tolerance. Knockout of PD-L1 on tumor cells or in mice completely eliminated the immunomodulatory effect of pomalidomide. Furthermore, pomalidomide synergized with other immunotherapies to improve anticancer therapy. Taken together, this study identifies a new mechanism for the immunomodulatory functions of pomalidomide in cancer therapy. These results also offer a clinical approach for blocking PD-L1 induction and potentially promoting antitumor immunity. SIGNIFICANCE: These findings report that the immunomodulatory drug pomalidomide, widely used to treat myeloma and other cancers, enhances antitumor immunity by inhibiting PD-1/PD-L1 expression.


Assuntos
Antineoplásicos/farmacologia , Antígeno B7-H1/genética , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Neoplasias/genética , Neoplasias/imunologia , Talidomida/análogos & derivados , Animais , Linhagem Celular Tumoral , Citotoxicidade Imunológica/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imunidade/efeitos dos fármacos , Melanoma Experimental , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Talidomida/farmacologia
12.
Ann Gastroenterol Surg ; 2(1): 65-71, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29863120

RESUMO

Pancreatic cancer is often resistant to chemotherapy. We previously showed the efficacy of combination treatment using gemcitabine and nafamostat mesilate (FUT-175) for patients with unresectable pancreatic cancer. However, the mechanisms that affect the sensitivity of FUT-175 are not fully understood. The purpose of the present study was to clarify the mechanism of the sensitivity to FUT-175, with a focus on the activity of glycogen synthase kinase-3ß (GSK-3ß). In vitro, we assessed sensitivity to FUT-175 in human pancreatic cancer cell lines (PANC-1 and MIAPaCa-2) and difference of signaling in these cells by cell proliferation assay, Western blot analysis and microarray. Next, we assessed cell viability, apoptotic signal and nuclear factor-kappa B (NF-κB) activity in response to treatment with FUT-175 alone and in combination with GSK-3 inhibitor or protein phosphatase 2A (PP2A) by cell proliferation assay, Western blot analysis and enzyme-linked immunosorbent assay. Phosphorylated GSK-3ß level was significantly higher in MIAPaCa-2 (high sensitivity cell) than in PANC-1 (low sensitivity cell). Cell viability and NF-κB activity were significantly decreased by addition of GSK-3 inhibitor to FUT-175, and levels of cleaved caspase-8 were increased by inhibition of GSK-3. PP2A inhibitor increased the levels of phosphorylated GSK-3ß and sensitized both cell lines to FUT-175 as measured by cell viability and apoptotic signal. The results indicate that GSK-3ß activity plays a key role in the antitumor effect of FUT-175 in pancreatic cancer cells, and regulation of GSK-3ß by PP2A inhibition could be a novel therapeutic approach for pancreatic cancer.

13.
Surgery ; 164(3): 404-410, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29754978

RESUMO

BACKGROUND: Liver function in patients with hepatocellular carcinoma is generally graded according to the Child-Pugh system; however, some variables in the Child-Pugh grade are subjective. We developed a novel, objective score called the prothrombin time-international normalized ratio to albumin ratio. The aim of this study was to evaluate the prognostic value of this new score in patients with hepatocellular carcinoma after hepatic resection. METHODS: The study comprised 199 patients who underwent elective hepatic resection for hepatocellular carcinoma between January 2003 and December 2014. We investigated retrospectively the relation between prothrombin time-international normalized ratio to albumin ratio, disease-free survival, and overall survival and compared the value of liver functional reserve between prothrombin time-international normalized ratio to albumin ratio and Child-Pugh grade. RESULTS: The optimal cut-off level of the prothrombin time-international normalized ratio to albumin ratio was 0.288. In multivariate analysis, the independent and significant predictors of cancer recurrence consisted of hepatitis C virus infection (P = .043), preoperative retention rate of indocyanine green at 15 minutes ≥15% (P = .039), the presence of multiple tumors (P = .001) or microvascular invasion (P < .001), and prothrombin time-international normalized ratio to albumin ratio ≥0.288 (P = .022). The independent predictors of poor overall survival were microvascular invasion (P = .001) and prothrombin time-international normalized ratio to albumin ratio ≥0.288 (P = .001). In patients with a high prothrombin time-international normalized ratio to albumin ratio, pathologic liver cirrhosis (P < .001), postoperative ascites (P = .039), and postoperative liver failure (P = .040) were greater than for their counterparts. CONCLUSION: The prothrombin time-international normalized ratio to albumin ratio may reflect liver function and may be a novel indicator of poor long-term outcome in patients with hepatocellular carcinoma after hepatic resection.


Assuntos
Carcinoma Hepatocelular/sangue , Coeficiente Internacional Normatizado , Neoplasias Hepáticas/sangue , Tempo de Protrombina , Albumina Sérica , Idoso , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Hepatectomia , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
14.
Mol Pharm ; 15(6): 2142-2150, 2018 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-29668291

RESUMO

Introducing siRNA into human immune cells by an artificial delivery system continues to be a challenging issue. We previously developed a multifunctional envelope-type nanodevice (MEND) containing the YSK12-C4, a fusogenic cationic lipid, (YSK12-MEND) and succeeded in the efficient delivery of siRNA into human immune cell lines. Significant cytotoxicity, however, was observed at siRNA doses needed for gene silencing in NK-92 cells. NK-92 cells, a unique natural killer (NK) cell line, would be applicable for use in clinical NK therapy. Thus, reducing the cytotoxicity of the YSK12-MEND in NK-92 cells would strengthen the efficacy of NK-92 cell-based therapy. The amount of the YSK12-C4 in the MEND needed to be reduced to reduce the cytotoxicity, because the cytotoxicity was directly associated with the YSK12-C4. In the present study, we decreased the total amount of lipid, including the YSK12-C4, by introducing a core formed by electrostatic interactions of siRNA with a polycation (protamine) (siRNA core), which led to a decrease in cytotoxicity in NK-92 cells. We prepared a YSK12-MEND containing an siRNA core (YSK12-MEND/core) at charge ratios (CR: YSK12-C4/siRNA) of 10, 5, 3, and 2.5 and compared the YSK12-MEND/core with that for a YSK12-MEND (CR16.9). Cell viability was increased by more than 2 times at a CR5 or less. On the other hand, the YSK12-MEND/core (CR5) maintained the same gene silencing efficiency (60%) as the YSK12-MEND. Interestingly, the cellular uptake efficiency and hemolytic activity of the YSK12-MEND/core (CR5) was reduced compared to that for the YSK12-MEND. In calculating the silencing activity per cellular uptake efficiency and hemolytic activity, the value for the YSK12-MEND/core (CR5) was more than 2 times as high as that of the YSK12-MEND. The fact indicates that after endosomal escape, the process can be enhanced by using a YSK12-MEND/core (CR5). Thus, introducing an siRNA core into lipid nanoparticles can be a potent strategy for decreasing cytotoxicity without an appreciable loss of gene silencing activity in NK-92 cells.


Assuntos
Engenharia Celular/métodos , Sistemas de Liberação de Medicamentos/métodos , Células Matadoras Naturais/metabolismo , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , Transferência Adotiva/métodos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inativação Gênica , Hemólise/efeitos dos fármacos , Humanos , Células Matadoras Naturais/transplante , Lipídeos/efeitos adversos , Lipídeos/química , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/efeitos adversos , Poliaminas/efeitos adversos , Poliaminas/química , RNA Interferente Pequeno/efeitos adversos
15.
Artigo em Inglês | MEDLINE | ID: mdl-29479338

RESUMO

Environmental chemicals are known to disrupt the endocrine system in humans and to have adverse effects on several organs including the developing brain. Recent studies indicate that exposure to environmental chemicals during gestation can interfere with neuronal differentiation, subsequently affecting normal brain development in newborns. Xenoestrogen, bisphenol A (BPA), which is widely used in plastic products, is one such chemical. Adverse effects of exposure to BPA during pre- and postnatal periods include the disruption of brain function. However, the effect of BPA on neural differentiation remains unclear. In this study, we explored the effects of BPA or bisphenol F (BPF), an alternative compound for BPA, on neural differentiation using ReNcell, a human fetus-derived neural progenitor cell line. Maintenance in growth factor-free medium initiated the differentiation of ReNcell to neuronal cells including neurons, astrocytes, and oligodendrocytes. We exposed the cells to BPA or BPF for 3 days from the period of initiation and performed real-time PCR for neural markers such as ß III-tubulin and glial fibrillary acidic protein (GFAP), and Olig2. The ß III-tubulin mRNA level decreased in response to BPA, but not BPF, exposure. We also observed that the number of ß III-tubulin-positive cells in the BPA-exposed group was less than that of the control group. On the other hand, there were no changes in the MAP2 mRNA level. These results indicate that BPA disrupts neural differentiation in human-derived neural progenitor cells, potentially disrupting brain development.

16.
Rinsho Ketsueki ; 58(11): 2256-2260, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29212978

RESUMO

A 76-year-old woman was operated on for rectal cancer in 2011 without chemotherapy and was followed up in the outpatient department. Decrease in white blood cell count was observed from 2013, and she developed anemia in 2015. Bone marrow aspiration was performed, and she was diagnosed with acute myeloid leukemia with myelodysplasia-related changes (AML/MRC). First, remission induction therapy was initiated with idarubicin and cytarabine administration, but pneumonia and vertebral osteomyelitis developed during the neutropenic period. Although the progress of antibiotics aided in the improvement of the recent prognosis of vertebral osteomyelitis compared with the past, poor prognosis with high death rate was still inevitable. Then, consolidation therapy was initiated with azacitidine (AZA) administration, and treatment was carried out for vertebral osteomyelitis with several antibiotics in parallel, which together led to the successful treatment of vertebral osteomyelitis while maintaining a remission state of AML. Because AZA is known to be well-tolerated and neutropenic phase is shorter than intensive chemotherapy in general, it can be an effective treatment option for patients who need both infection control and AML treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Osteomielite/etiologia , Pneumonia/etiologia , Doenças da Coluna Vertebral/etiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução , Leucemia Mieloide Aguda/complicações , Osteomielite/tratamento farmacológico , Doenças da Coluna Vertebral/tratamento farmacológico , Resultado do Tratamento
17.
J Pharmacol Sci ; 134(4): 234-238, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28844423

RESUMO

The anticoagulant effect of rivaroxaban, a direct inhibitor of activated factor X (FX), might be influenced by its dosing time because the activity of the coagulofibrinolytic system exhibits daily rhythmicity. In rats, FX activity follows a 24-h rhythm with a peak in the middle of the light phase and a trough at the beginning of the dark phase. Consistent with these findings, a single dose of rivaroxaban had a stronger inhibitory effect on FX activity after dosing at the beginning of the light phase than after dosing at the beginning of the dark phase. A similar chronopharmacological effect was seen in a quantitative model of venous stasis thrombosis. In comparison, the dosing time had minimal influence on the pharmacokinetics of rivaroxaban. These data indicate that the anticoagulant effect of rivaroxaban is influenced by the dosing time. Further studies should confirm this finding in a clinical setting.


Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/fisiologia , Cronofarmacocinética , Ritmo Circadiano/fisiologia , Cronoterapia Farmacológica , Inibidores do Fator Xa/farmacologia , Rivaroxabana/administração & dosagem , Rivaroxabana/farmacologia , Animais , Relação Dose-Resposta a Droga , Fator X/fisiologia , Masculino , Fotoperíodo , Ratos Wistar , Rivaroxabana/farmacocinética , Fatores de Tempo
18.
Oncol Lett ; 14(1): 293-298, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28693167

RESUMO

Systemic inflammation, as evidenced by the Glasgow prognostic score (GPS), predicts cancer-specific survival in various cancer types. The aim of this study was to evaluate the significance of the GPS in the therapeutic outcome of the patient following surgical resection for hepatocellular carcinoma. In total, 144 patients underwent surgical resection for hepatocellular carcinoma. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: Patients with normal serum albumin (<3.5 g/dl) and normal serum C-reactive protein (CRP) (≤1.0 mg/dl) were classified as GPS 0 (n=76), those with low serum albumin (<3.5 g/dl) or elevated serum CRP (>1.0 mg/dl) were classified as GPS 1 (n=58), and those with low serum albumin (<3.5 g/dl) and elevated serum CRP (>1.0 mg/dl) were classified as GPS 2 (n=10). Retrospectively, the relationship between patient characteristics including GPS, disease-free as well as overall survival were investigated. In disease-free survival, GPS 2 (P=0.019), with a tumor number ≥3 (P=0.004), and positive portal or venous invasion (P=0.034) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, GPS 1 (P=0.042), GPS 2 (P<0.001) and positive portal or venous invasion (P<0.001) were independent predictors of poor patient outcome according to multivariate analysis. To conclude, the GPS in patients with hepatocellular carcinoma is an independent prognostic predictor after hepatic resection.

19.
Anticancer Res ; 37(6): 3215-3219, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28551667

RESUMO

BACKGROUND/AIM: Preoperative biliary drainage (PBD) is often performed for jaundiced patients. However, the optimal duration of PBD remains unknown. The aim of this study was to investigate whether duration of PBD influenced the prognosis of patients after pancreaticoduodenectomy (PD) for pancreatic head cancer. PATIENTS AND METHODS: Twenty-five patients who underwent PD for pancreatic head cancer with obstructive jaundice between 2007 and 2013 were included. Tumor and host factors were analyzed to evaluate their potential prognostic effects and patients' characteristics between the two groups according to the duration of PBD were analyzed. RESULTS: In multivariate analysis, overall survival, duration of PBD ≥21 days and tumor-node-metastasis (TNM) stage III or IV were significant predictors. Duration of PBD ≥21 days was positively correlated with higher level of serum C-reactive protein (CRP), modified Glasgow prognostic score (mGPS) and neoadjuvant therapy. CONCLUSION: Duration of PBD is an independent prognostic factor after PD for pancreatic head cancer with obstructive jaundice.


Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/métodos , Drenagem/métodos , Icterícia Obstrutiva/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Procedimentos Cirúrgicos do Sistema Biliar/mortalidade , Distribuição de Qui-Quadrado , Drenagem/efeitos adversos , Drenagem/mortalidade , Feminino , Humanos , Icterícia Obstrutiva/diagnóstico , Icterícia Obstrutiva/etiologia , Icterícia Obstrutiva/mortalidade , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
20.
Cardiology ; 137(4): 237-243, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28467980

RESUMO

OBJECTIVES: Retropharyngeal lesions are often associated with Kawasaki disease (KD). A 4-year-old male first presented a peritonsillar and retropharyngeal abscess-like lesion. Surgical tonsillectomy was performed to avoid a risk of mediastinal abscess, but he fulfilled the diagnostic criteria of KD after the operation. This prompted us to perform a histological study on the KD tonsils. METHODS: The histopathology of the KD tonsil specimens were compared with hypertrophic tonsils obtained from 4 patients with chronic tonsillitis unrelated to KD assessed by the immunostainings. RESULTS: KD tonsils showed small lymphatic follicles and neutrophil infiltration in the peritonsillar muscle layer, with no evidence of vasculitis or abscess formation. The KD tonsils exclusively showed (1) predominant activated CD4+ T cells in the perifollicular interstitium, (2) sparse scattering of CD68+ monocytes/macrophages in the lymphatic follicles, and (3) polyclonal carcinoembryonic antigen-positive cells in the lymphatic follicles and venules with the high endothelial cells. CONCLUSIONS: The uniquely distributed immunocytes suggest the inflammatory process of KD involving the pathogen-associated molecules.


Assuntos
Linfadenopatia/diagnóstico por imagem , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/patologia , Pescoço/diagnóstico por imagem , Tonsila Palatina/patologia , Linfócitos T CD4-Positivos/citologia , Pré-Escolar , Doença Crônica , Diagnóstico Diferencial , Feminino , Humanos , Macrófagos/citologia , Masculino , Monócitos/citologia , Síndrome de Linfonodos Mucocutâneos/complicações , Padrões Moleculares Associados a Patógenos , Tomografia Computadorizada por Raios X , Tonsilectomia , Tonsilite/cirurgia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA