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1.
J Microbiol Immunol Infect ; 56(5): 921-930, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37562996

RESUMO

BACKGROUND: The efficacy of inhaled corticosteroid (ICS) in the treatment of patients with COVID-19 has been evaluated in randomized controlled trials (RCTs), however, their findings are not consistent. METHODS: PubMed, Embase, Cochrane Library, ClinicalTrials.gov, Scopus, Web of Science and Google Scholar were searched to June 10, 2023. Only RCTs that investigated the clinical efficacy and safety of ICS for patients with COVID-19 were included. RESULTS: Eleven RCTs were included. ICS users had significantly higher rate of symptom alleviation at day 14 than the control group (risk ratio [RR], 1.13; 95% CI, 1.04-1.23; I2 = 42%). Additionally, no significant difference between the ICS users and the control group was observed in the composite outcome of urgent care, emergency department (ED) visit or hospitalization (RR, 0.43; 95% CI, 0.08-2.48; I2 = 85%) and hospitalization or death (RR, 0.85; 95% CI, 0.64-1.12; I2 = 0%). Finally, ICS user had a non-significantly lower risk of death at day 28 than the control group (0.63% vs 0.99%; RR, 0.82; 95% CI, 0.43-1.56; I2 = 0%). CONCLUSIONS: Additional ICS use, particularly inhaled budesonide may help symptom relief in patients with COVID-19. However, ICS use did not help reduce the risk of urgent care, ED visit, hospitalization, or death.

2.
Front Pharmacol ; 14: 1206366, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554990

RESUMO

Background: The efficacy of cuttlebone for treating hyperphosphatemia in patients with end-stage renal disease and its safety remained unclear. Methods: Randomized controlled trials comparing the efficacy of cuttlebone with conventional interventions were retrieved from MEDLINE, EMBASE, Cochrane Library, Airiti Library, and other major Chinese databases until 1 February 2023. The primary outcome was circulating phosphate concentration, while secondary outcomes included circulating calcium and intact parathyroid hormone levels, calcium-phosphorus product, and treatment-related side-effects. Results: Analysis of nine studies published between 2000 and 2019 including 726 participants showed a lower circulating phosphate concentration in the cuttlebone group than in controls [mean difference (MD) = -0.23, 95% CI: -0.39 to -0.06, p = 0.006, I2 = 94%, 726 patients] and a dose-dependent effect of cuttlebone against hyperphosphatemia. Therapeutic benefits were noted after both short-term (1-2 months) and long-term (3-6 months) treatments. Besides, patients receiving hemodialysis showed a better response to cuttlebone than those receiving peritoneal dialysis. There was no difference in circulating calcium level (mean difference = 0.03, 95% CI: -0.01 to 0.07, p = 0.17, I2 = 34%, 654 patients), while patients receiving cuttlebone showed lower circulating iPTH level and calcium-phosphorus product (MD = -43.63, 95% CI: -74.1 to -13.16, p = 0.005, I2 = 76%, 654 patients), (MD = -0.38, 95% CI: -0.38 to -0.01, p = 0.04, I2 = 83%, 520 patients). No difference in the risks of constipation, gastrointestinal discomfort, and elevated blood calcium was noted between the two groups. Conclusion: Compared with conventional phosphate-binding agents, cuttlebone more efficiently suppressed hyperphosphatemia with a dose-dependent effect. The limited number of included studies warrants further clinical investigations to verify our findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023396300.

3.
Int J Antimicrob Agents ; 62(1): 106830, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37100354

RESUMO

OBJECTIVE: To assess the clinical efficacy and safety of novel antibiotics for complicated urinary tract infections (cUTIs). METHODS: Three electronic databases (Medline, Embase and the Cochrane Library) were searched from inception until 20 October 2022 to identify randomized controlled trials (RCTs) investigating the efficacy and safety of novel antibiotics (novel ß-lactam/ß-lactamase inhibitor combinations, aminoglycosides, fluoroquinolones and cefiderocol) against cUTIs. The primary outcome was the clinical cure rate (CCR) at test of cure (TOC), while secondary outcomes included CCR at end of treatment (EOT), microbiological eradication rate, and the risk of adverse events (AEs). Trial sequential analysis (TSA) was used to examine the evidence. RESULTS: In total, 11 RCTs demonstrated a higher CCR [83.6% vs 80.3%, odds ratio (OR) 1.37, 95% confidence interval (CI) 1.08-1.74, P=0.01, I2=35%, 11 RCTs, 3514 participants] and microbiological eradication rate (77.7% vs 67.2%, OR 1.79, 95% CI 1.46-2.20, P<0.00001, 11 RCTs, 4347 participants) at TOC in the intervention group compared with the control group. At EOT, there was no significant difference in CCR (OR 0.96, P=0.81, I2=4%, nine RCTs, 3429 participants) or risk of treatment-emergent AEs (OR 0.95, P=0.57, I2=51%, 11 RCTs, 5790 participants) between the intervention and control groups. TSA showed robust evidence regarding microbiological eradication rate and treatment-emergent AEs, while the CCR at TOC and EOT remained inconclusive. CONCLUSIONS: While showing similar safety, the investigated novel antibiotics may be more effective than the conventional antibiotics for patients with cUTIs. However, as the pooled evidence relating to CCR remained inconclusive, further studies are required to address this issue.


Assuntos
Antibacterianos , Infecções Urinárias , Humanos , Antibacterianos/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Inibidores de beta-Lactamases/uso terapêutico , Resultado do Tratamento
4.
Healthcare (Basel) ; 10(8)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35893191

RESUMO

The introductory pharmacy practice experiences (IPPE) in Taiwan, which are traditionally conducted in physical hospital settings, incorporated up to 30% distance learning from May 2021 due to Coronavirus Disease 2019 (COVID-19). A web-based cross-sectional survey was adopted to investigate pharmacy students' experiences and perceptions of transitioning from in-hospital internships to distance learning due to COVID-19 in the pharmacy department of a university in Southern Taiwan. We analyzed the results to discover factors that significantly affected students' perceptions of transitioning from in-hospital internships to distance learning. In total, 81 interns from the university's pharmacy department responded to the questionnaire. Approximately half of the participants felt happy when they learned, before the internship began, that the internship would be partially replaced with distance learning. The overall satisfaction rate was 67.9%, and no significant differences was observed in students' satisfaction between hospital size or distance-learning time. However, more students in the medical center felt they had insufficient time to finish assignments compared to those in the regional hospitals, and the students who had 11-15 days of distance learning felt that they interacted more smoothly with their peers compared to those who had other durations. Program designers should make distance internship courses more student-centered, with a focus on increasing interactions between students, teachers, and peers to compensate for the lack of physical presence.

5.
Zoonoses Public Health ; 69(8): 904-914, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35818968

RESUMO

Toxoplasmosis caused by Toxoplasma gondii affects both conservation and public health efforts. In the Taipei Zoo, toxoplasmosis was diagnosed in ring-tailed lemurs and a meerkat in 2019 while a freeze-thaw meat strategy had been applied to carnivores before the event. To investigate the possible risk factors associated with T. gondii infection in the Taipei Zoo, 179 veterinary visiting mammals from 2019-2021 and six stray cats were included to detect anti-T. gondii IgG and IgM in their serum via ELISA, and T. gondii in their faeces and blood via PCR. Although the overall T. gondii IgG seroprevalence was 33.5% and PCR positivity was 16.2% in the zoo mammals, the correlation between T. gondii PCR and systemic IgG results was low. An omnivorous diet (adjusted OR = 0.4; 95% CI: 0.2-1.0), a herbivorous diet (adjusted OR = 3.2; 95% CI: 1.1-9.6), and animals in the Conservation Area where stray cats appeared (adjusted OR = 18.3; 95% CI: 3.9-85.9) were independent risk factors for T. gondii infection. The low T. gondii-specific IgM positivity (0.6%) suggests that most animals did not have acute T. gondii infection. In conclusion, our findings indirectly support that feeding frozen meat to carnivores, cleaning fresh food, and restricting access to stray cats to prevent faecal contaminants could prevent animals from T. gondii exposure.


Assuntos
Doenças do Gato , Toxoplasma , Toxoplasmose Animal , Gatos , Animais , Toxoplasmose Animal/diagnóstico , Toxoplasmose Animal/epidemiologia , Estudos Soroepidemiológicos , Anticorpos Antiprotozoários , Mamíferos , Fatores de Risco , Imunoglobulina M , Imunoglobulina G , Doenças do Gato/epidemiologia
6.
IEEE/ACM Trans Comput Biol Bioinform ; 19(6): 3135-3143, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34748498

RESUMO

Considerable sequence data are produced in genome annotation projects that relate to molecular levels, structural similarities, and molecular and biological functions. In structural genomics, the most essential task involves resolving protein structures efficiently with hardware or software, understanding these structures, and assigning their biological functions. Understanding the characteristics and functions of proteins enables the exploration of the molecular mechanisms of life. In this paper, we examine the problems of protein classification. Because they perform similar biological functions, proteins in the same family usually share similar structural characteristics. We employed this premise in designing a classification algorithm. In this algorithm, auxiliary graphs are used to represent proteins, with every amino acid in a protein to a vertex in a graph. Moreover, the links between amino acids correspond to the edges between the vertices. The proposed algorithm classifies proteins according to the similarities in their graphical structures. The proposed algorithm is efficient and accurate in distinguishing proteins from different families and outperformed related algorithms experimentally.


Assuntos
Algoritmos , Proteínas , Humanos , Proteínas/genética , Proteínas/química , Software , Genoma
7.
J Comp Pathol ; 188: 26-31, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34686274

RESUMO

A 9-year-old male captive savannah monitor (Varanus exanthematicus) with a history of general debility was submitted for necropsy. Grossly, there were multiple white masses in the colon, mesorchium and tracheal adventitia. Histologically, the lesions were composed of epithelioid to spindloid neoplastic cells arranged in sheets to interlacing and interwoven bundles, and separated by abundant myxoid material or extensive stromal hyalinization and fibrosis with occasional chondroid metaplasia. Perivascular infiltration of epithelioid neoplastic cells was occasionally seen. Neoplastic cells were immunopositive for alpha-smooth muscle actin, melan-A and S100. The unique histological features and concurrent myogenic and melanocytic immunophenotypes suggest a malignant perivascular epithelioid cell tumour. To our knowledge, this is the first report of perivascular epithelioid cell tumours in a non-human species.


Assuntos
Lagartos , Neoplasias de Células Epitelioides Perivasculares , Sarcoma , Animais , Células Epitelioides , Antígeno MART-1 , Masculino , Neoplasias de Células Epitelioides Perivasculares/veterinária , Sarcoma/veterinária
8.
Artigo em Inglês | MEDLINE | ID: mdl-34065894

RESUMO

Unplanned patient readmission (UPRA) is frequent and costly in healthcare settings. No indicators during hospitalization have been suggested to clinicians as useful for identifying patients at high risk of UPRA. This study aimed to create a prediction model for the early detection of 14-day UPRA of patients with pneumonia. We downloaded the data of patients with pneumonia as the primary disease (e.g., ICD-10:J12*-J18*) at three hospitals in Taiwan from 2016 to 2018. A total of 21,892 cases (1208 (6%) for UPRA) were collected. Two models, namely, artificial neural network (ANN) and convolutional neural network (CNN), were compared using the training (n = 15,324; ≅70%) and test (n = 6568; ≅30%) sets to verify the model accuracy. An app was developed for the prediction and classification of UPRA. We observed that (i) the 17 feature variables extracted in this study yielded a high area under the receiver operating characteristic curve of 0.75 using the ANN model and that (ii) the ANN exhibited better AUC (0.73) than the CNN (0.50), and (iii) a ready and available app for predicting UHA was developed. The app could help clinicians predict UPRA of patients with pneumonia at an early stage and enable them to formulate preparedness plans near or after patient discharge from hospitalization.


Assuntos
Readmissão do Paciente , Pneumonia , Humanos , Redes Neurais de Computação , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Curva ROC , Taiwan/epidemiologia
9.
Viruses ; 12(10)2020 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-33023277

RESUMO

Generation of a safe, economical, and effective vaccine capable of inducing mucosal immunity is critical for the development of vaccines against enteric viral diseases. In the current study, virus-like particles (VLPs) containing the spike (S), membrane (M), and envelope (E) structural proteins of porcine epidemic diarrhea virus (PEDV) expressed by the novel polycistronic baculovirus expression vector were generated. The immunogenicity and protective efficacy of the PEDV VLPs formulated with or without mucosal adjuvants of CCL25 and CCL28 (CCL25/28) were evaluated in post-weaning pigs. While pigs intramuscularly immunized with VLPs alone were capable of eliciting systemic anti-PEDV S-specific IgG and cellular immunity, co-administration of PEDV VLPs with CCL25/28 could further modulate the immune responses by enhancing systemic anti-PEDV S-specific IgG, mucosal IgA, and cellular immunity. Upon challenge with PEDV, both VLP-immunized groups showed milder clinical signs with reduced fecal viral shedding as compared to the control group. Furthermore, pigs immunized with VLPs adjuvanted with CCL25/28 showed superior immune protection against PEDV. Our results suggest that VLPs formulated with CCL25/28 may serve as a potential PEDV vaccine candidate and the same strategy may serve as a platform for the development of other enteric viral vaccines.


Assuntos
Quimiocinas CC/metabolismo , Quimiocinas/metabolismo , Imunidade nas Mucosas/imunologia , Vírus da Diarreia Epidêmica Suína/imunologia , Doenças dos Suínos/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas Virais/imunologia , Adjuvantes Imunológicos , Animais , Anticorpos Antivirais , Infecções por Coronavirus/prevenção & controle , Fezes/virologia , Imunidade Celular , Células Sf9 , Suínos , Doenças dos Suínos/virologia , Vacinação , Eliminação de Partículas Virais
10.
Vaccines (Basel) ; 8(1)2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32102459

RESUMO

Intramuscular (IM) immunization is generally considered incapable of generating a protective mucosal immune response. In the swine industry, attempts to develop a safe and protective vaccine for controlling porcine epidemic diarrhea (PED) via an IM route of administration have been unsuccessful. In the present study, porcine chemokine ligand proteins CCL25, 27, and 28 were constructed and stably expressed in the mammalian expression system. IM co-administration of inactivated PEDV (iPEDV) particles with different CC chemokines and Freund's adjuvants resulted in recruiting CCR9+ and/or CCR10+ inflammatory cells to the injection site, thereby inducing superior systemic PEDV specific IgG, fecal IgA, and viral neutralizing antibodies in pigs. Moreover, pigs immunized with iPEDV in combination with CCL25 and CCL28 elicited substantial protection against a virulent PEDV challenge. We show that the porcine CC chemokines could be novel adjuvants for developing IM vaccines for modulating mucosal immune responses against mucosal transmissible pathogens in pigs.

11.
Opt Express ; 27(18): 25072-25077, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31510386

RESUMO

Visible light communication (VLC) can provide a dedicated, secure, and high data rate wireless transmission link. It has gained considerable attentions recently, and is considered as one of the promising technologies for beyond 5G mobile and wireless communications. In this work, we demonstrate a VLC system with a recorded data rate of 40.665 Gbit/s using tricolor red, green and blue (RGB) laser diodes (LDs) and polarization multiplexing. 2 m free-space transmission distance is achieved. The implementation of bit-loading, power-loading, and polarization multiplexing are discussed. Experimental bit-error-ratio (BER) results show that each of the 6 polarization and wavelength de-multiplexed channels can achieve the forward-error-correction (FEC) requirement.

12.
Opt Express ; 27(11): 16377-16383, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31163815

RESUMO

We propose and experimentally demonstrate a practical visible light position (VLP) system using repeated unit cells and machine learning (ML) algorithms. ML is employed to increase the positioning accuracy. Algorithms of the 2nd-order regression ML model and the polynomial trilateral ML model are discussed. More than 80% of the measurement data have position error within 4 cm when using the 2nd-order regression ML model, while the position error is within 5 cm when using the polynomial trilateral ML model.

13.
Sci Rep ; 7(1): 9656, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28851883

RESUMO

In this study, the effect of 3-2-(2-aminoethylamino) ethylamino propyl trimethoxysilane (ETAS) modification and post rapid thermal annealing (RTA) treatment on the adhesion of electroless plated nickel-phosphorus (ELP Ni-P) film on polyvinyl alcohol-capped palladium nanoclusters (PVA-Pd) catalyzed silicon wafers is systematically investigated. Characterized by pull-off adhesion, atomic force microscopy, X-ray spectroscopy and water contact angle, a time-dependent, three-staged ETAS grafting mechanism including islandish grafting, a self-assembly monolayer (SAM) and multi-layer grafting is proposed and this mechanism is well correlated to the pull-off adhesion of ELP Ni-P film. In the absence of RTA, the highest ELP Ni-P film adhesion occurs when ETAS modification approaches SAM, where insufficient or multi-layer ETAS grafting fails to provide satisfactory results. On the other hand, if RTA is applied, the best ELP Ni-P film adhesion happens when ETAS modification is islandish owing to the formation of nickel silicide, where SAM or multi-layer ETAS modification cannot provide satisfactory adhesion because the interaction between ETAS and PVA-Pd has been sabotaged during RTA. Evidenced by microstructural images, we also confirmed that ETAS can act as an efficient barrier layer for nickel diffusion to bulk silicon.

14.
Biomed Res Int ; 2016: 6205158, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27990433

RESUMO

Although previous studies demonstrated the risk of ischemic stroke (IS) in patients with head and neck cancer (HNC), the impact of oral antithrombotic therapy (OAT) on this risk has not yet been assessed. We aimed to evaluate the effectiveness and safety of OAT in patients with HNC treated with RT. This retrospective cohort study was performed using the National Health Insurance Research Database of Taiwan. A total of 37,638 patients diagnosed with HNC included in the study were classified as users and nonusers of OAT. Primary outcome was IS or transient ischemic attack (TIA), and secondary outcomes were death and major bleeding. The Cox proportional hazards model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). There was no significant difference in the risk of IS or TIA between patients on continuous OAT and nonusers (adjusted HR, 0.812; 95% CI, 0.199-3.309). The risk of major bleeding was not significantly different between the groups. From a national population database, we did not find an association between OAT and decreasing risk of ischemic stroke/TIA or increasing hazard of major bleeding.


Assuntos
Fibrinolíticos/administração & dosagem , Neoplasias de Cabeça e Pescoço/radioterapia , Hemorragia/prevenção & controle , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose/epidemiologia , Trombose/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Hemorragia/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevenção Primária/estatística & dados numéricos , Lesões por Radiação/epidemiologia , Lesões por Radiação/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Taiwan/epidemiologia , Resultado do Tratamento
15.
Opt Express ; 24(3): 1973-8, 2016 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-26906773

RESUMO

Based on the rolling shutter effect of the complementary metal-oxide-semiconductor (CMOS) image sensor, bright and dark fringes can be observed in each received frame. By demodulating the bright and dark fringes, the visible light communication (VLC) data logic can be retrieved. However, demodulating the bright and dark fringes is challenging as there is a high data fluctuation and large extinction ratio (ER) variation in each frame due. Hence proper thresholding scheme is needed. In this work, we propose and compare experimentally three thresholding schemes; including third-order polynomial curve fitting, iterative scheme and quick adaptive scheme. The evaluation of these three thresholding schemes is performed.

17.
Invest New Drugs ; 31(4): 801-11, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23224353

RESUMO

Nanoliposomes are good drug delivery systems that allow the encapsulation of drugs into vesicles for their delivery. The objective of this study is to investigate the therapeutic efficacy of a new radio-therapeutics of (188)Re-labeled pegylated liposome in a C26 murine colon carcinoma solid tumor model. The safety of (188)Re-liposome was evaluated before radiotherapy treatment. The anti-tumor effect of (188)Re-liposome was assessed by tumor growth inhibition, survival ratio and ultrasound imaging. Apoptotic marker in tumor was also evaluated by the TUNEL (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling) method after injection of (188)Re-liposome. The group treated with (188)Re-liposome displayed slight loss in body weight and decrease in white blood cell (WBC) count 7 to 14 days post-injection. With respect to therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome showed better mean tumor growth inhibition rate (MGI) and longer median survival time (MGI = 0.140; 80 day) than those treated with anti-cancer drug 5-FU (MGI = 0.195; 69 day) and untreated control mice (MGI = 0.413; 48 day). The ultrasound imaging showed a decrease in both tumor volume and number of blood vessels. There were significantly more apoptotic nuclei (TUNEL-positive) in (188)Re-liposome-treated mice at 8 h after treatment than in control mice. These results evidenced the potential benefits achieved by oncological application of the radio-therapeutics (188)Re-liposome for adjuvant cancer treatment.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Etilenodiaminas/uso terapêutico , Lipossomos/uso terapêutico , Compostos Organometálicos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Etilenodiaminas/administração & dosagem , Etilenodiaminas/toxicidade , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Injeções Intravenosas , Marcação por Isótopo , Lipossomos/administração & dosagem , Lipossomos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/toxicidade , Análise de Sobrevida , Resultado do Tratamento , Ultrassonografia
18.
Cancer Biother Radiopharm ; 27(8): 481-9, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23067100

RESUMO

Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p<0.05) was significantly better than those of 5-FU (48.25 days; p>0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.


Assuntos
Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/radioterapia , Fluoruracila/análogos & derivados , Fluoruracila/farmacologia , Compostos Radiofarmacêuticos/farmacologia , Rênio/farmacologia , Animais , Linhagem Celular Tumoral , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Modelos Animais de Doenças , Fluoruracila/farmacocinética , Humanos , Lipossomos/farmacocinética , Lipossomos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Cintilografia , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Aleatória , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Oncol Rep ; 28(5): 1736-42, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22922965

RESUMO

Liposomes are good candidates as drug carriers and have been widely investigated in drug delivery systems. In this study, a new combination of bimodal 188Re-(DXR)-liposome-BBN radiochemotherapeutics was designed and studied for treating solid pancreatic tumor by intravenous administration. The in vivo nuclear microSPECT/CT imaging of tumor targeting, prolonged survival time and therapeutic efficacy were evaluated in AR42J malignant pancreatic solid tumor-bearing nude mice. MicroSPECT/CT imaging of 188Re-liposome-BBN pointed to significant targeting in tumors at 24 h after intravenous injection (SUV=2.13 ± 0.98). Co-injection of a blocking dose of cold BBN (4 mg/kg) inhibited the accumulation of 188Re-liposome-BBN in tumors (SUV=1.82 ± 0.31). For therapeutic efficacy, inhibition of tumor growth in mice treated with 188Re-DXR-liposome-BBN was precisely controlled [mean growth inhibition rate (MGI) = 0.092] and had longer survival time [life-span (LS) = 86.96%] than those treated with anticancer drug 188Re-liposome-BBN (MGI = 0.130; LS = 75%), Lipo-Dox-BBN (MGI = 0.666; LS = 3.61%) and untreated control mice. An additive tumor regression effect was observed (CI 0.946) for co-delivery of 188Re-DXR-liposome-BBN radiochemotherapeutics. These results point to the potential benefit of the 188Re-(DXR)-liposome-BBN radiochemotherapeutics for adjuvant cancer treatment with applications in oncology.


Assuntos
Bombesina/uso terapêutico , Doxorrubicina/uso terapêutico , Neoplasias Pancreáticas/terapia , Rênio/uso terapêutico , Administração Intravenosa , Animais , Bombesina/farmacologia , Linhagem Celular Tumoral , Quimiorradioterapia , Doxorrubicina/farmacologia , Humanos , Camundongos , Imagem Multimodal , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/mortalidade , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/farmacologia , Compostos Radiofarmacêuticos/uso terapêutico , Rênio/química , Rênio/farmacologia , Distribuição Tecidual , Tomografia Computadorizada por Raios X , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Int J Nanomedicine ; 6: 2607-19, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22114492

RESUMO

BACKGROUND: Nanoliposomes are designed as carriers capable of packaging drugs through passive targeting tumor sites by enhanced permeability and retention (EPR) effects. In the present study the biodistribution, pharmacokinetics, micro single-photon emission computed tomography (micro-SPECT/CT) image, dosimetry, and therapeutic efficacy of (188)Re-labeled nanoliposomes ((188)Re-liposomes) in a C26 colonic peritoneal carcinomatosis mouse model were evaluated. METHODS: Colon carcinoma peritoneal metastatic BALB/c mice were intravenously administered (188)Re-liposomes. Biodistribution and micro-SPECT/CT imaging were performed to determine the drug profile and targeting efficiency of (188)Re-liposomes. Pharmacokinetics study was described by a noncompartmental model. The OLINDA|EXM computer program was used for the dosimetry evaluation. For therapeutic efficacy, the survival, tumor, and ascites inhibition of mice after treatment with (188)Re-liposomes and 5-fluorouracil (5-FU), respectively, were evaluated and compared. RESULTS: In biodistribution, the highest uptake of (188)Re-liposomes in tumor tissues (7.91% ± 2.02% of the injected dose per gram of tissue [%ID/g]) and a high tumor to muscle ratio (25.8 ± 6.1) were observed at 24 hours after intravenous administration. The pharmacokinetics of (188)Re-liposomes showed high circulation time and high bioavailability (mean residence time [MRT] = 19.2 hours, area under the curve [AUC] = 820.4%ID/g*h). Micro-SPECT/CT imaging of (188)Re-liposomes showed a high uptake and targeting in ascites, liver, spleen, and tumor. The results were correlated with images from autoradiography and biodistribution data. Dosimetry study revealed that the (188)Re-liposomes did not cause high absorbed doses in normal tissue but did in small tumors. Radiotherapeutics with (188)Re-liposomes provided better survival time (increased by 34.6% of life span; P < 0.05), tumor and ascites inhibition (decreased by 63.4% and 83.3% at 7 days after treatment; P < 0.05) in mice compared with chemotherapeutics of 5-fluorouracil (5-FU). CONCLUSION: The use of (188)Re-liposomes for passively targeted tumor therapy had greater therapeutic effect than the currently clinically applied chemotherapeutics drug 5-FU in a colonic peritoneal carcinomatosis mouse model. This result suggests that (188)Re-liposomes have potential benefit and are safe in treating peritoneal carcinomatasis of colon cancer.


Assuntos
Fluoruracila/farmacocinética , Lipossomos/farmacocinética , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/metabolismo , Radioisótopos/farmacocinética , Compostos Radiofarmacêuticos/farmacocinética , Rênio/farmacocinética , Animais , Ascite/metabolismo , Ascite/patologia , Fluoruracila/uso terapêutico , Injeções Intravenosas , Estimativa de Kaplan-Meier , Lipossomos/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Peritoneais/química , Neoplasias Peritoneais/patologia , Doses de Radiação , Radioisótopos/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , Rênio/uso terapêutico , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único , Microtomografia por Raio-X , Ensaios Antitumorais Modelo de Xenoenxerto
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