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1.
ACS Appl Mater Interfaces ; 12(4): 4254-4264, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31927943

RESUMO

In the present study, we utilize a poly[2-(N,N-dimethylamino)ethyl methacrylate]-poly(ε-caprolactone) (PDMA-PCL) micellar template-based gold nanoshell as a nanocarrier of a platinum-based chemotherapeutic drug, dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt). The gold nanoshells not only function as a drug delivery platform but also provide a remarkable photothermal effect, resulting in synergistically combined chemo-photothermal therapy. With the positively charged outstretched hydrophilic PDMA segments, chloroauric anions are attracted to the PDMA-PCL micellar surface and reduced to gold atoms in situ, forming small seeds that nucleate the subsequent growth of gold nanoshells. The DACHPt-loaded gold nanoshells possess strong absorption in the near-infrared (NIR) region and outstanding photothermal conversion effect; thus, they can promote a temperature increase that is sufficient to ablate tumor cells under NIR laser irradiation at a moderate power density (1 W/cm2). Furthermore, by exploiting the synergistic effects of platinum-based chemotherapy and photothermal therapy, the DACHPt-loaded gold nanoshells exhibited a profound inhibition of tumor growth compared to chemotherapy or photothermal therapy alone. Therefore, the platinum(II)-loaded gold nanoshells that we proposed herein may be a potential alternative for efficient curative therapy for colorectal cancer.

2.
Colloids Surf B Biointerfaces ; 173: 788-797, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30384276

RESUMO

Cancer is a complex and tenacious disease. Drug-delivery systems in combination with multimodal therapy strategies are very promising candidates for cancer theranostic applications. In this study, a new drug-delivery vehicle that combine human serum albumin (HSA)- and poly(sodium 4-styrenesulfonate) (PSS)-coated gold nanorod nanoparticles(GNR/PSS/HSA NPs) was developed for synergistic cancer therapy. Doxorubicin (DOX) was loaded onto GNR/PSS/HSA NPs, by electrostatic and hydrophobic forces, to create multimodal DOX@GNR/PSS/HSA NPs. DOX@GNR/PSS/HSA NPs were found to be highly biocompatible and stable in physiological solutions. Furthermore, GNR/PSS/HSA NPs with or without DOX were designed to exhibit strong absorbance in the near-infrared region and high photothermal conversion efficiency. Therefore, bimodal DOX release from DOX@GNR/PSS/HSA NPs could be triggered by an acidic pH and by near-infrared irradiation after NPs preferentially accumulated at tumor sites, leading to a significant chemotherapeutic effect. Moreover, DOX@GNR/PSS/HSA NPs were designed to be applied during chemo- and photo-thermal combination therapy and exhibited a synergistic anticancer effect that was superior to the effect of monotherapy, from both in vitro and in vivo results. These results suggest that DOX@GNR/PSS/HSA NPs are a strong candidate for a nanoplatform for future antitumor therapeutic strategies.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Preparações de Ação Retardada , Doxorrubicina/farmacologia , Terapia de Alvo Molecular/métodos , Nanotubos/química , Neoplasias/terapia , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Terapia Combinada/métodos , Doxorrubicina/química , Doxorrubicina/metabolismo , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Ouro/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Injeções Subcutâneas , Terapia com Luz de Baixa Intensidade/métodos , Camundongos , Camundongos Nus , Polímeros/química , Albumina Sérica Humana/química , Ácidos Sulfônicos/química , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Intest Res ; 17(1): 54-62, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30449079

RESUMO

BACKGROUND/AIMS: Incidences of inflammatory bowel diseases (IBDs), ulcerative colitis (UC), and Crohn's disease (CD), have been increasing in Asia. In this study, we report the relevant clinical characteristics and determined the epidemiological trend of IBD in Taiwan from 2001 to 2015. METHODS: A retrospective study was conducted to analyze data recorded from January 2001 through December 2015 in the registered database compiled by the National Health Insurance and provided by the Ministry of Health and Welfare, Taiwan. RESULTS: A total of 3,806 patients with catastrophic IBD illness were registered from 2001 to 2015 in Taiwan (CD, 919; UC, 2,887). The crude incidence of CD increased from 0.17/100,000 in 2001 to 0.47/100,000 in 2015, whereas that of UC increased from 0.54/100,000 in 2001 to 0.95/100,000 in 2015. The prevalence of CD increased from 0.6/100,000 in 2001 to 3.9/100,000 in 2015, whereas that of UC increased from 2.1/100,000 in 2001 to 12.8/100,000 in 2015. The male-to-female ratio in the study sample was 2.19 for CD and 1.62 for UC. The median age of those registered with CD was lower than that of those registered for UC: 38.86 and 44.86 years, respectively. A significantly greater increase in CD incidence rate was identified among 20 to 39-year-old compared with other age groups. CONCLUSIONS: Using Taiwan's nationwide insurance database, we determined that the number of patients with CD increased more rapidly during the study period than the number of patients with UC, especially among age 20 to 39-year-old, resulting in a decreased UC-to-CD ratio.

4.
Photodiagnosis Photodyn Ther ; 23: 111-118, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29894822

RESUMO

Photodynamic therapy (PDT) is a treatment utilizing the combined action of photosensitizers and light for the treatment of various cancers. The mechanisms for tumor destruction after PDT include direct tumor cell kill by singlet oxygen species (OS), indirect cell kill via vascular damage, and an elicited immune response. However, it has been reported that many cellular activators, including vascular endothelial growth factor (VEGF), are produced by tumor cells after PDT. In this study, we demonstrate that meta-tetra(hydroxyphenyl) chlorin (mTHPC)-based photodynamic therapy combined with bevacizumab (Avastin™), an anti-VEGF neutralizing monoclonal antibody that blocks the binding of VEGF to its receptor, can enhance the effectiveness of each treatment modality. We evaluated the efficacy of bevacizumab-based anti-angiogenesis in combination with PDT as well as the resulting VEGF levels and microvessel density (MVD) in a mouse model of human colon cancer. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were performed to assess VEGF concentrations and microvessel density in the various treatment groups, and confocal imaging and high performance liquid chromatography (HPLC) analyses were used to measure the distribution and concentration of mTHPC in tumors. Our results demonstrate that combination of PDT followed by bevacizumab significantly elicits a greater tumor response whereas bevacizumab treatment prior to PDT led to a reduced tumor response. Immunostaining and ELISA analyses revealed a lower expression of VEGF in tumors treated with combination therapy of PDT followed by bevacizumab. However, bevacizumab treatment decreased the accumulation of mTHPC in tumors 24 h after administration, which complemented the results of decreased anti-tumor efficacy of bevacizumab followed by PDT.


Assuntos
Inibidores da Angiogênese/farmacologia , Bevacizumab/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Mesoporfirinas/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Estimativa de Kaplan-Meier , Mesoporfirinas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Carga Tumoral , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Mol Pharm ; 15(4): 1432-1444, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29498860

RESUMO

Photodynamic therapy (PDT) has been shown to kill cancer cells and improve survival and quality of life in cancer patients, and numerous new approaches have been considered for maximizing the efficacy of PDT. In this study, a new multifunctional nanophotosensitizer Ce6/GE11-(pH)micelle was developed to target epidermal growth factor receptor (EGFR) overexpressing colorectal cancer (CRC) cells. This nanophotosensitizer was synthesized using a micelle comprising pH-responsive copolymers (PEGMA-PDPA), biodegradable copolymers (mPEG-PCL), and maleimide-modified biodegradable copolymers (Mal-PEG-PCL) to entrap the potential hydrophobic photosensitizer chlorin e6 (Ce6) and to present EGFR-targeting peptides (GE11) on its surface. In the presence of Ce6/GE11-(pH)micelles, Ce6 uptake by EGFR-overexpressing CRC cells significantly increased due to GE11 specificity. Moreover, Ce6 was released from Ce6/GE11-(pH)micelles in tumor environments, leading to improved elimination of cancer cells in PDT. These results indicate enhanced efficacy of PDT using Ce6/GE11-(pH)micelle, which is a powerful nanophotosensitizer with high potential for application to future PDT for CRC.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/terapia , Receptores ErbB/metabolismo , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Animais , Linhagem Celular Tumoral , Células HCT116 , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Micelas , Peptídeos/química , Polímeros/química
6.
Bioconjug Chem ; 29(4): 1384-1398, 2018 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-29505243

RESUMO

Recently, nanoparticles (NPs) have been widely investigated for delivery of anticancer drugs. Here, a dual control drug-release modality was developed that uses naturally occurring protein apoferritin loaded with doxorubicin (DOX) and ADS-780 near-infrared (NIR) fluorescent dye-decorated NPs (ADNIR NPs). ADNIR NPs act as a grenade to detonate the targeted tumor site following laser irradiation (photothermal therapy, PTT) and explode into cluster warheads (apoferritin-loaded DOX nanocages, AF-DOX NCs) that further destroy the tumor cells (chemotherapy). Light was shown to disrupt the grenade-like structure of NPs to release AF-DOX NCs as well as DOX from NCs in low-pH intercellular environments. In vitro and in vivo studies showed that the structure of AF-DOX NCs was disassembled to release DOX, which then killed the cancer cells in organelles with acidic environments. In vivo studies showed that the ADNIR NP-decorated with NIR dye facilitated tracking of the accumulated NPs at the tumor site using an IVIS imaging system. Overall, targeted ADNIR NPs with dual-release mechanisms were developed for use in photothermal theranostic and chemotherapy. This modality has high potential for application in cancer treatment and clinical translation for drug delivery and imaging.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/terapia , Doxorrubicina/uso terapêutico , Corantes Fluorescentes/uso terapêutico , Nanopartículas/uso terapêutico , Nanomedicina Teranóstica/métodos , Animais , Antibióticos Antineoplásicos/administração & dosagem , Apoferritinas/administração & dosagem , Apoferritinas/uso terapêutico , Neoplasias do Colo/patologia , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/uso terapêutico , Doxorrubicina/administração & dosagem , Sistemas de Liberação de Medicamentos , Feminino , Corantes Fluorescentes/administração & dosagem , Células HT29 , Humanos , Hipertermia Induzida/métodos , Raios Infravermelhos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Imagem Óptica/métodos , Fototerapia/métodos
7.
ACS Appl Mater Interfaces ; 10(7): 6096-6106, 2018 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-29368506

RESUMO

Apoferritin (AF) is a natural nontoxic iron carrier and has a natural hollow structure that can be used to deliver small molecules. The surface of AF has many amine functional groups that can be modified to create targeted ligands. We loaded oxaliplatin onto AF, which was then used as a template to conjugate with panitumumab via a polyethylene glycol linker. The oxaliplatin-loaded AF conjugated with panitumumab (AFPO) was designed to specifically target cell lines expressing epidermal growth factor receptor (EGFR). AFPO efficiently released oxaliplatin and suppressed tumor cell growth. Furthermore, the novel AFPO nanocages showed significant inhibition and greater accumulation in tumor models with high EGFR expression in vivo. Our study revealed that combining panitumumab and oxaliplatin into one formulation (AFPO nanocage) could be a promising shortcut in clinical applications.


Assuntos
Apoferritinas/química , Neoplasias Colorretais , Receptores ErbB , Humanos , Concentração de Íons de Hidrogênio , Panitumumabe , Platina
8.
FASEB J ; 32(3): 1705-1715, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29146731

RESUMO

Reporter proteins have broad applications in visualizing molecular events at the cellular, tissue and whole-body levels. Transmembrane transporters recognizing specific molecular domains are of particular interest because they enable the migration of signal-source molecules from the extracellular space to the cytoplasm for subsequent application in multimodality imaging. Organic anion-transporting polypeptides (OATPs) have demonstrated their MRI reporter efficacy. We further expanded their use as a dual-modality reporter in MRI and noninvasive in vivo imaging system (IVIS). We overexpressed OATP1B3 in the HT-1080 sarcoma cell line. Both Gd-EOB-DTPA, an MRI contrast agent, and indocyanine green (ICG), a near-infrared fluorescent dye that provides better deep-tissue detection because of its long wavelength, could be delivered to the intracellular space and imaged in a tumor-bearing nude mouse model. Our in vivo dual-imaging reporter system achieved high sensitivity in MRI and observation periods lasting as long as 96 h in IVIS. Because of the superior temporal and spatial resolutions and the clinical availability of both ICG and Gd-EOB-DTPA, this dual-imaging OATP1B3 system will find biomedical use in tumor biology, stem cell trafficking, and tissue engineering.-Wu, M.-R., Liu, H.-M., Lu, C.-W., Shen, W.-H., Lin, I.-J., Liao, L.-W., Huang, Y.-Y., Shieh, M.-J., Hsiao, J.-K. Organic anion-transporting polypeptide 1B3 as a dual reporter gene for fluorescence and magnetic resonance imaging.


Assuntos
Genes Reporter , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Imagem por Ressonância Magnética , Sarcoma , Animais , Linhagem Celular Tumoral , Xenoenxertos , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Imagem Óptica , Sarcoma/diagnóstico por imagem , Sarcoma/genética , Sarcoma/metabolismo
9.
Mol Pharm ; 14(8): 2766-2780, 2017 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-28703590

RESUMO

Cancer research regarding near-infrared (NIR) agents for chemothermal therapy (CTT) has shown that agents with specific functions are able to inhibit tumor growth. The aim of current study was to optimize CTT efficacy for treatment of colorectal cancer (CRC) by exploring strategies which can localize high temperature within tumors and maximize chemotherapeutic drug uptake. We designed a new and simple multifunctional NIR nanoagent composed of the NIR cyanine dye, polyethylene glycol, and a cyclic arginine-glycine-aspartic acid peptide and loaded with the anti-CRC chemotherapeutic agent, 7-ethyl-10-hydroxy-camptothecin (SN38). Each component of this nanoagent exhibited its specific functions that help boost CTT efficacy. The results showed that this nanoagent greatly strengthens the theranostic effect of SN38 and CTT against CRC due to its NIR imaging ability, photothermal, enhanced permeability and retention (EPR) effect, reticuloendothelial system avoidance, and angiogenic blood vessel-targeting properties. This NIR nanoagent will help facilitate development of new strategies for treating CRC.


Assuntos
Nanomedicina Teranóstica/métodos , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/química , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Humanos , Indóis/química , Indóis/uso terapêutico , Irinotecano , Nanopartículas/química , Fototerapia/métodos
10.
Intest Res ; 15(3): 266-284, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28670225

RESUMO

Ulcerative colitis (UC) is an inflammatory bowel disease characterized by chronic mucosal inflammation of the colon, and the prevalence and incidence of UC have been steadily increasing in Taiwan. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of UC taking into account currently available evidence and the expert opinion of the committee. Accurate diagnosis of UC requires thorough clinical, endoscopic, and histological assessment and careful exclusion of differential diagnoses, particularly infectious colitis. The goals of UC therapy are to induce and maintain remission, reduce the risk of complications, and improve quality of life. As outlined in the recommended treatment algorithm, choice of treatment is dictated by severity, extent, and course of disease. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to immunosuppressive treatment, especially with steroids and biologic agents, and should be regularly monitored for reactivation of latent infection. These consensus statements are also based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of UC in Taiwan.

11.
Intest Res ; 15(3): 285-310, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28670226

RESUMO

Crohn's disease (CD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. CD is rare in Taiwan and other Asian countries, but its prevalence and incidence have been steadily increasing. A steering committee was established by the Taiwan Society of Inflammatory Bowel Disease to formulate statements on the diagnosis and management of CD taking into account currently available evidence and the expert opinion of the committee. Thorough clinical, endoscopic, and histological assessments are required for accurate diagnosis of CD. Computed tomography and magnetic resonance imaging are complementary to endoscopic evaluation for disease staging and detecting complications. The goals of CD management are to induce and maintain remission, reduce the risk of complications, and improve quality of life. Corticosteroids are the mainstay for inducing re-mission. Immunomodulating and biologic therapies should be used to maintain remission. Patients should be evaluated for hepatitis B virus and tuberculosis infection prior to treatment and receive regular surveillance for cancer. These consensus statements are based on current local evidence with consideration of factors, and could be serve as concise and practical guidelines for supporting clinicians in the management of patients with CD in Taiwan.

12.
Adv Healthc Mater ; 6(13)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28418176

RESUMO

Targeted combination chemotherapy (TCT) has recently been used to increase the induction of tumor cell death. In particular, the combination of Panitumumab and the platinum (Pt)-derived chemotherapeutic drug Oxaliplatin is clinically effective against KRAS and BRAF wild-type colorectal cancer (CRC) cells that overexpress epidermal growth factor receptors, and significantly greater efficacy is observed than with either drug alone. However, low accumulation of Pt drug in tumor sites prevents achievement of ideal efficacy. To develop an alternative drug therapy that achieves the ideal efficacy of TCT, the novel nanomedicine NANOPt-Pan using self-assembled dichloro(1,2-diaminocyclohexane)Pt(II)-modified Panitumumab is generated. Treatments with NANOPt-Pan lead to significant accumulation of Pt drug and Panitumumab in tumors, reflecting enhanced permeability and retention effect, active targeting, and sustained circulation of the Pt drug in the blood. In addition, NANOPt-Pan has excellent in vivo anti-CRC efficacy. These data indicate that NANOPt-Pan has high potential as a candidate nanomedicine for CRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/tratamento farmacológico , Portadores de Fármacos , Nanomedicina , Nanopartículas , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/química , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Células CACO-2 , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Humanos , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacocinética , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Panitumumabe , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Control Release ; 258: 196-207, 2017 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-28445743

RESUMO

The purpose of this research was to investigate the effectiveness of epidermal growth factor receptor (EGFR) targeted micelles loaded with IR-780 (Cetuximab/IR-780/micelles) for generating tumor targeting, multimodal images, and photothermal therapy (PTT). We initially studied the cellular uptake of these micelles using the HCT-116 and SW-620 cell lines. HCT-116 (high expression of EGFR) and SW-620 (low expression of EGFR) cell lines were used to examine biodistribution and antitumor effects of Cetuximab/IR-780/micelles. Time-lapse near-IR fluorescence (NIRF) images also indicated the highest IR-780 accumulation from Cetuximab/IR-780/micelles in HCT-116 tumors (p<0.05). HCT-116 tumors in tumor-bearing mice exhibited significantly higher accumulations of Cetuximab/IR-780/111In-micelles than SW-620 tumors in Micro-SPECT/CT imaging and biodistribution studies (p<0.05). Dual-radioisotope Nano-SPECT/CT imaging of Cetuximab/131I-IR-780/111In-micelles demonstrated simultaneous high accumulation of both IR-780 and micelles in HCT-116 tumors, but not in SW-620 tumors. Regarding antitumor effects, following the Cetuximab/IR-780/micelles with PPT on day 6, all HCT-116 tumor-bearing mice were cured. In contrast, SW-620 tumors relapsed at 13days after treatment. In summary, we expect that the Cetuximab/IR-780/micelles could enhance the antitumor effects by PTT in EGFR overexpression colorectal cancers through effective drug delivery nanoparticles.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/terapia , Sistemas de Liberação de Medicamentos , Indóis/administração & dosagem , Animais , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/uso terapêutico , Autorradiografia , Cetuximab/farmacocinética , Cetuximab/uso terapêutico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/metabolismo , Receptores ErbB/metabolismo , Feminino , Células HCT116 , Humanos , Hipertermia Induzida/métodos , Indóis/farmacocinética , Indóis/uso terapêutico , Camundongos Nus , Micelas , Fototerapia/métodos , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único
14.
BMC Gastroenterol ; 17(1): 28, 2017 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-28193173

RESUMO

BACKGROUND: Colitis is exacerbated in patients with concurrent cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). We assessed the prevalence and clinical features of CMV colitis in hospitalized IBD patients. METHODS: A retrospective study reviewed the data from January 1, 1998 through December 31, 2013 compiled at the National Taiwan University Hospital. The CMV colitis patients' demographic data, clinical information, treatment regimens, pathologic findings, and outcome were analyzed. RESULTS: A total of 673 IBD patients were hospitalized during the study period. There were 312 patients diagnosed with Crohn's disease (CD) and 361 with ulcerative colitis (UC). CMV colitis was diagnosed as having positive inclusion bodies in colonic tissue. Six of the 312 CD patients (1.9%) and five of the 361 UC patients (1.4%) were diagnosed with CMV colitis. Compared to CD patients without CMV colitis, patients with CMV colitis were more often older (p < 0.005). Higher steroid usage was noted in the CMV positive group compared to age and gender matched CMV negative IBD patients (81.8% vs. 51.5%). Eight patients received ganciclovir treatment. Three patients who did not receive antiviral treatment had colitis flare-ups after the index admission. CONCLUSIONS: The prevalence of CMV colitis in hospitalized IBD inpatients was 1.6% in Taiwan. Two associated factors for CMV colitis in hospitalized IBD patients were that they were elderly in CD and were on higher doses of steroids. Routine histopathology studies and/or PCR for refractory colitis patients are suggested to diagnose CMV colitis. Once the diagnosis is made, antiviral treatment is recommended to decrease the colitis relapse rate.


Assuntos
Colite Ulcerativa/virologia , Colite/epidemiologia , Doença de Crohn/virologia , Infecções por Citomegalovirus/epidemiologia , Citomegalovirus , Adolescente , Adulto , Criança , Colite/complicações , Colite/virologia , Colo/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/virologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta/estatística & dados numéricos , Estudos Retrospectivos , Taiwan/epidemiologia , Adulto Jovem
15.
J Formos Med Assoc ; 116(11): 880-887, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28215672

RESUMO

BACKGROUND/PURPOSE: Pleurodesis with biomaterial membrane is an emerging treatment method for pneumothorax. However, the ideal one for the common disease is still under debate. METHODS: We investigate the Poly-ε-caprolactone (PCL) membrane pleurodesis by using New Zealand White rabbits, which was sacrificed for examination one month later. Moreover, inflammation and fibrosis scoring were done under microscopic evaluation, as well as Western blot analysis in vitro and in vivo. RESULTS: Gross evaluation of pleurodesis score revealed that dense PCL membrane produced moderate pleural adhesion, while porous PCL membrane exhibited significantly higher pleurodesis scores. CONCLUSION: PCL membrane induced significant degree of adhesion, both within the abdomen and chest of the rabbits. The porous PCL membrane produces more intensive adhesion than dense one. Fibronectin plays an important role in the process of pleurodesis. Further study is required for the clinical application of the promising material.


Assuntos
Teste de Materiais , Membranas Artificiais , Pleurodese/métodos , Poliésteres/administração & dosagem , Animais , Linhagem Celular , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumotórax/terapia , Coelhos
16.
Carbohydr Polym ; 155: 101-108, 2017 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-27702492

RESUMO

The high- and low-molecular weight hyaluronic acid (HHA and LHA) were used to conjugate with PLGA-PEG copolymers which were applied to encapsulate DOTAP/pDNA (D/P) lipoplex as a CD44-targeted micelle delivery system. The size and zeta potential of DNA loaded micelles were measured. The cytotoxicity and cellular transfection of DNA loaded micelles were performed in CD44-positive MDA-MB-231 and MCF-7 cancer cells and CD44-negative HepG2 cells. The endocytosis mechanism of micelles was investigated further. The DNA loaded HA-conjugated micelles possessed negative-charged character which prevented erythrocytes from agglutination. Both LHA-PEG-PLGA and HHA-PEG-PLGA micelles had comparable cellular viability in L929 normal cells. The cellular transfection of HHA-PEG-PLGA micelles was much higher than of LHA-PEG-PLGA micelles in CD44-positive cells. The specific and strong binding of HHA to CD44-positive cells resulted in the cellular transfection of HHA-PEG-PLGA micelles in CD44-positive cells significantly higher than in CD44-negative cells.


Assuntos
Técnicas de Transferência de Genes , Receptores de Hialuronatos/metabolismo , Ácido Hialurônico/química , Micelas , Linhagem Celular Tumoral , Sobrevivência Celular , Ácidos Graxos Monoinsaturados , Humanos , Polietilenoglicóis , Poliglactina 910 , Compostos de Amônio Quaternário
17.
Tissue Eng Part A ; 23(5-6): 185-194, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27814669

RESUMO

The use of autologous fat grafting in breast reconstruction still requires optimization. Fat survival and calcification are the main issues that affect the outcomes of the procedure. In this study, a cell-based therapy utilizing laminin-alginate beads (LABs) as carriers was proposed to promote cell survival and adipogenesis by providing short-term physical support and facilitate nutrient diffusion of the implants. Laminin-modified alginate beads were fabricated by immobilizing laminin onto ring-opened alginate, used to encapsulate 3T3-L1 preadipocytes, and evaluated in vitro and in vivo. LABs as preadipocyte carriers showed better biocompatibility and stability than unmodified alginate beads. Preadipocytes in LABs had higher survival rate and enhanced adipogenesis than those in unmodified alginate beads. In vivo studies showed that LABs gradually degraded and the sites were replaced by newly formed fat tissues, and new blood vessels were also observed. 7T-MRI study mimicking clinical fat grafting showed that LABs carrying adipose stem cells improved the results of conventional fat grafts. Therefore, we believe that LABs represent promising cell carriers and can be potentially used for the reconstruction of breasts or other soft tissues in the future.


Assuntos
Adipócitos , Adipogenia , Alginatos/química , Células Imobilizadas , Laminina/química , Células 3T3-L1 , Adipócitos/metabolismo , Adipócitos/transplante , Animais , Células Imobilizadas/metabolismo , Células Imobilizadas/transplante , Feminino , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Ratos Sprague-Dawley
18.
Mater Sci Eng C Mater Biol Appl ; 70(Pt 1): 599-606, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27770932

RESUMO

Chitosan nanoparticles modified with 10 and 30% urocanic acid (CUA) via carbodiimide crosslinking were examined for an efficient gene delivery carrier. The CUA gene carrier was characterized by FTIR, TEM, SEM and the in vitro transfection efficiency CUA polyplex was tested with HeLa and 3T3 cells. The loading efficiency of CUA complexes with DNA was assessed at different N/P ratio of 1, 2, 4, 6, 8, and 10. The DNA loading efficiency was found be to >85% for chitosan, CUA10 and CUA30% and the DNA protection ability of CUA10 and CUA30 nanoparticle complexes was confirmed upon incubation with NheI and HindIII. The cell toxicity and cell viability results have supported the non-toxic nature of CUA10 and CUA30 nanoparticles. In vitro transfection efficiency of CUA10 and CUA30 polyplex was tested for EGFP expression in 3T3 and HeLa cells and a relative maximum % transfection of about 10% was confirmed by CUA10 and CUA30 after 96h transfection. The feasibility and biocompatibility of CUA gene carrier in transgenic chickens was also demonstrated. The in vitro transfection and in vivo embryonic viability studies further confirmed the CUA as promising gene carrier because of the improved biocompatibility and DNA protection ability.


Assuntos
Quitosana/química , Técnicas de Transferência de Genes , Ácido Urocânico/química , Células 3T3 , Animais , Animais Geneticamente Modificados , Morte Celular , Sobrevivência Celular , Embrião de Galinha , DNA/metabolismo , Endonucleases/metabolismo , Células HeLa , Humanos , Camundongos , Nanopartículas/química , Ninidrina/química , Tamanho da Partícula , Plasmídeos/metabolismo , Mapeamento por Restrição , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Transfecção
19.
Biomater Sci ; 4(12): 1742-1753, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27722406

RESUMO

The development of a controlled-release drug delivery system has been an important objective for cancer therapy. To achieve the goal of sustained drug release for preventing the biotoxicity of platinum drugs, oxaliplatin was encapsulated into PEGylated multiwalled carbon nanotubes (MWNTs) decorated with superparamagnetic iron oxide (SPIO) for magnetic resonance imaging (MRI). The superparamagnetic properties and purification of SPIO/MWNT composites were achieved by annealing treatment during the fabrication process; the better hydrophilicity and biocompatibility were also accomplished subsequently after modification with polyethylene glycol (PEG). Oxa/MagMWNT-PEG 7 presented the ability of sustained release, as only 36.25% of loaded oxaliplatin leaked within 12 h and 55.48% lasted over 144 h. An in vitro study revealed that compared with free oxaliplatin and Oxa/MagMWNT 8, Oxa/MagMWNT-PEG 7 showed a slightly decreased cytotoxic effect when the cell viability was assessed at 12 and 24 h; however, a drastic enhancement in cytotoxicity was observed at 96 h. Platinum-DNA quantification on HCT116 cells showed that the internalization of oxaliplatin lasted up to 96 h, which was due to the sustained release of nanomedicine. An in vivo study showed that the nanomedicine-treated group exhibited effective antitumor efficacy similar to the free drug-treated group, but without inducing death in mice. After intravenous administration, the T2-weighted MRI signal revealed that Oxa/MagMWNT-PEG7 had an excellent MRI enhancement in the tumor region. This SPIO-decorated MWNT composite encapsulated with antitumor drugs could potentially be useful for treatments, such as cancer therapy and MRI.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Preparações de Ação Retardada/química , Imagem por Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Nanotubos de Carbono/química , Compostos Organoplatínicos/administração & dosagem , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Sobrevivência Celular , Liberação Controlada de Fármacos , Células HCT116 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organoplatínicos/química , Compostos Organoplatínicos/farmacologia , Oxaliplatina , Tamanho da Partícula , Polietilenoglicóis/química , Propriedades de Superfície , Distribuição Tecidual
20.
Int J Nanomedicine ; 11: 3357-69, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27524894

RESUMO

A novel thermosensitive polymer p(N-isopropylacrylamide-co-poly[ethylene glycol] methyl ether acrylate)-block-poly(epsilon-caprolactone), p(NIPAAM-co-PEGMEA)-b-PCL, was synthesized and developed as nanomicelles. The hydrophobic heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin and the photosensitizer cyanine dye infrared-780 were loaded into the core of the micelles to achieve both chemotherapy and photothermal therapy simultaneously at the tumor site. The release of the drug could be controlled by varying the temperature due to the thermosensitive nature of the micelles. The micelles were less than 200 nm in size, and the drug encapsulation efficiency was >50%. The critical micelle concentrations were small enough to allow micelle stability upon dilution. Data from cell viability and animal experiments indicate that this combination treatment using photothermal therapy with chemotherapy had synergistic effects while decreasing side effects.


Assuntos
Micelas , Temperatura , Resinas Acrílicas/síntese química , Resinas Acrílicas/química , Animais , Antineoplásicos/farmacologia , Benzoquinonas/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Quimioterapia Combinada , Células HCT116 , Humanos , Indóis/farmacologia , Raios Infravermelhos , Lactamas Macrocíclicas/farmacologia , Camundongos Nus , Camundongos SCID , Peso Molecular , Poliésteres/síntese química , Poliésteres/química
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