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1.
Macromol Rapid Commun ; 43(10): e2200006, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35316561

RESUMO

High-performance supercapacitors based on activated carbons (AC) derived from polyethylene (PE), which is one of the most abundant plastic materials worldwide, are fabricated. First, PE carbons (PEC) are prepared via sulfonation, which is a reported solution for successful carbonization of innately non-carbonizable PE. Then, the physico-electrical changes of PECs upon a chemical activation process are explored. Interestingly, upon the chemical activation, PECs are converted ACs with a large surface area and high crystallinity at the same time. Subsequently, PE-derived ACs (PEAC) are exploited as electrode materials for supercapacitors. Resultant supercapacitors based on PEACs exhibit impressive performance. When compared to supercapacitors based on YP50f, representative commercial ACs, devices using PEACs presented considerably good capacitance, low resistance, and great rate capability. Specifically, the retention rate of devices using PEACs is significantly higher than that of YP50f-based devices. At the high rate of charge-discharge situation reaching 7 A g-1 , the capacitance of supercapacitors using PEACs is ≈70% higher than that of YP50f-based devices. It is assumed that the carbon structure accompanying both large surface area and high conductivity endows a great electrochemical performance at the high current operating conditions. Therefore, it is envisioned that PE may be a viable candidate electrode material for commercially available supercapacitors.

2.
Kidney Int ; 100(1): 206-214, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33647326

RESUMO

HLA-incompatible living donor kidney transplantation (LDKT) is one of efforts to increase kidney transplantation opportunity for sensitized patients with kidney failure. However, there are conflicting reports for outcomes of HLA-incompatible kidney transplantation compared to patients who wait for HLA-compatible deceased donor kidney transplantation (DDKT) in the United States and United Kingdom. Waiting for an HLA-compatible DDKT is relatively disadvantageous in Korea, because the average waiting time is more than five years. To study this further, we compared outcomes of HLA-incompatible LDKT with those who wait for HLA-compatible DDKT in Korea. One hundred eighty nine patients underwent HLA-incompatible LDKT after desensitization between 2006 and 2018 in two Korean hospitals (42 with a positive complement-dependent cytotoxicity cross-match, 89 with a positive flow cytometric cross-match, and 58 with a positive donor-specific antibody with negative cross-match). The distribution of matched variables was comparable between the HLA-incompatible LDKT group and the matched control groups (waiting-list-only group; and the waiting-list-or-HLA-compatible-DDKT groups; 930 patients each). The HLA-incompatible LDKT group showed a significantly better patient survival rate compared to the waiting-list-only group and the waiting-list-or-HLA-compatible-DDKT groups. Furthermore, the HLA-incompatible LDKT group showed a significant survival benefit as compared with the matched groups at all strength of donor-specific antibodies. Thus, HLA-incompatible LDKT could have a survival benefit as compared with patients who were waitlisted for HLA-compatible DDKT or received HLA-compatible DDKT in Korea. This suggests that HLA-incompatible LDKT as a good option for sensitized patients with kidney failure in countries with prolonged waiting times for DDKT.


Assuntos
Transplante de Rim , Listas de Espera , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Doadores Vivos , República da Coreia , Reino Unido , Estados Unidos
3.
World J Urol ; 39(2): 407-413, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32335733

RESUMO

PURPOSE: Urological oncologists have difficulty providing optimal personalized care due to rapid alterations in scientific research results, medical advancements, and treatment guidelines. IBM's Watson for Oncology (WFO) is an artificial intelligence clinical decision-support system that assists oncologists with evidence-based treatment recommendations. In the present study, we examined the level of concordance between the treatment recommendations for prostate cancer according to WFO and the actual treatments that the patients received in the department of urology. METHODS: We enrolled 201 patients who received prostate cancer treatment between January 2018 and June 2018. WFO provided treatment recommendations using clinical data in three categories: recommended, for consideration, and not recommended. These were compared with the actual treatments received by patients. Prostate cancer treatments were considered concordant if the received treatments were included in the "recommended" or "for consideration" categories by WFO. RESULTS: The patients' mean age was 71.2 years. There were 60 (29.9%) and 114 (56.7%) patients with an Eastern Cooperative Oncology Group (ECOG) performance score ≥ 1 and non-organ confined disease (stage III/IV), respectively. The overall prostate cancer treatment concordance rate was 73.6% ("recommended": 53.2%; "for consideration": 20.4%). An ECOG performance score ≥ 1 and older age (≥ 75 years) were significantly associated with discordance (p = 0.001 and p = 0.026, respectively) on multivariate analysis. CONCLUSION: In the present study, the treatment recommendations by WFO and the actual received treatments in the department of urology showed a relatively high concordance rate in prostate cancer patients.


Assuntos
Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Oncologia/métodos , Neoplasias da Próstata/terapia , Urologia/métodos , Humanos , Masculino , Guias de Prática Clínica como Assunto
4.
J Am Chem Soc ; 141(17): 7037-7045, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30964997

RESUMO

The formation of inorganic nanoparticles has been understood based on the classical crystallization theory described by a burst of nucleation, where surface energy is known to play a critical role, and a diffusion-controlled growth process. However, this nucleation and growth model may not be universally applicable to the entire nanoparticle systems because different precursors and surface ligands are used during their synthesis. Their intrinsic chemical reactivity can lead to a formation pathway that deviates from a classical nucleation and growth model. The formation of metal oxide nanoparticles is one such case because of several distinct chemical aspects during their synthesis. Typical carboxylate surface ligands, which are often employed in the synthesis of oxide nanoparticles, tend to continuously remain on the surface of the nanoparticles throughout the growth process. They can also act as an oxygen source during the growth of metal oxide nanoparticles. Carboxylates are prone to chemical reactions with different chemical species in the synthesis such as alcohol or amine. Such reactions can frequently leave reactive hydroxyl groups on the surface. Herein, we track the entire growth process of iron oxide nanoparticles synthesized from conventional iron precursors, iron-oleate complexes, with strongly chelating carboxylate moieties. Mass spectrometry studies reveal that the iron-oleate precursor is a cluster comprising a tri-iron-oxo core and carboxylate ligands rather than a mononuclear complex. A combinatorial analysis shows that the entire growth, regulated by organic reactions of chelating ligands, is continuous without a discrete nucleation step.

5.
BJU Int ; 121(2): 225-231, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28834084

RESUMO

OBJECTIVE: To investigate the peri-operative and oncological outcomes of robot-assisted radical prostatectomy (RARP) in patients with oligometastatic prostate cancer (PCa). PATIENTS AND METHODS: We retrospectively reviewed the records of 79 patients with oligometastatic PCa treated with RARP or androgen deprivation therapy (ADT) between 2005 and 2015 at our institution. Of these 79 patients, 38 were treated with RARP and 41 were treated with ADT without local therapy. Oligometastatic disease was defined as the presence of five or fewer hot spots detected by preoperative bone scan. We evaluated peri-operative outcomes, progression-free survival (PFS), and cancer-specific survival (CSS). We analysed data using Kaplan-Meier methods, with log-rank tests and multivariate Cox regression models. RESULTS: Patients treated with RARP experienced similar postoperative complications to those previously reported in RP-treated patients, and fewer urinary complications than ADT-treated patients. PFS and CSS were longer in RARP-treated compared with ADT-treated patients (median PFS: 75 vs 28 months, P = 0.008; median CSS: not reached vs 40 months, P = 0.002). Multivariate analysis further identified RARP as a significant predictor of PFS and CSS (PFS: hazard ratio [HR] 0.388, P = 0.003; CSS: HR 0.264, P = 0.004). CONCLUSIONS: We showed that RARP in the setting of oligometastatic PCa is a safe and feasible procedure which improves oncological outcomes in terms of PFS and CSS. In addition, our data suggest that RARP effectively prevents urinary tract complications from PCa. The study highlights results from expert surgeons and highly selected patients that cannot be extrapolated to all patients with oligometastatic PCa; to confirm our findings, large, prospective, multicentre studies are required.


Assuntos
Neoplasias Ósseas/secundário , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Antagonistas de Androgênios/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Doenças Urológicas/etiologia
6.
Nanomedicine ; 14(1): 195-204, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28982587

RESUMO

Exosomes have recently emerged as a promising drug delivery system with low immunogenicity, high biocompatibility, and high efficacy of delivery. We demonstrated earlier that macrophage-derived exosomes (exo) loaded with a potent anticancer agent paclitaxel (PTX) represent a novel nanoformulation (exoPTX) that shows high anticancer efficacy in a mouse model of pulmonary metastases. We now report the manufacture of targeted exosome-based formulations with superior structure and therapeutic indices for systemic administration. Herein, we developed and optimized a formulation of PTX-loaded exosomes with incorporated aminoethylanisamide-polyethylene glycol (AA-PEG) vector moiety to target the sigma receptor, which is overexpressed by lung cancer cells. The AA-PEG-vectorized exosomes loaded with PTX (AA-PEG-exoPTX) possessed a high loading capacity, profound ability to accumulate in cancer cells upon systemic administration, and improved therapeutic outcomes. The combination of targeting ability with the biocompatibility of exosome-based drug formulations offers a powerful and novel delivery platform for anticancer therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Exossomos/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Macrófagos/química , Paclitaxel/administração & dosagem , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/química , Células Cultivadas , Portadores de Fármacos/química , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/química , Polietilenoglicóis/química
7.
J Korean Med Sci ; 33(15): e113, 2018 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-29629517

RESUMO

BACKGROUND: To investigate whether addition of amikacin to fluoroquinolone (FQ) antimicrobial prophylaxis reduces infections after transrectal ultrasound-guided prostate biopsy (TRUSPB). METHODS: A total of 503 patients undergoing rectal swab were divided into three groups. Patients with FQ-sensitive rectal flora (group 1, n = 248) were administered ciprofloxacin before TRUSPB, and patients with FQ-resistant rectal flora were either administered ciprofloxacin (group 2, n = 97) or amikacin and ciprofloxacin (group 3, n = 158) before TRUSPB. RESULTS: Based on the rectal swab, FQ resistance was 54.9%, and extended-spectrum ß-lactamase (ESBL) positivity was 17.2%. The incidence of infectious complication in group 1 was 1.6%. Groups 2 and 3, with FQ-resistant rectal flora, tended to have increased infectious complications (5.2% and 4.4%, respectively) but the difference between those results is not statistically significant. The most common pathogens of infectious complications in patients with FQ-resistant rectal flora were FQ-resistant and ESBL-producing Escherichia coli. E. coli pathogens isolated in Group 3 were amikacin-susceptible species. The operation history and ESBL positivity of rectal flora increased the incidence of infectious complications (odds ratio [OR] = 3.68; P = 0.035 and OR = 4.02; P = 0.008, respectively). DM and antibiotics exposure were risk factors for FQ resistance (OR = 2.19; P = 0.002) and ESBL positivity of rectal flora (OR = 2.96; P = 0.005), respectively. CONCLUSION: Addition of amikacin to ciprofloxacin prophylaxis could not reduce infectious complications in patients with FQ-resistant rectal flora. Despite the amikacin sensitivity of infectious complications, single-dose amikacin addition to ciprofloxacin prophylaxis has limitations.


Assuntos
Amicacina/uso terapêutico , Antibacterianos/uso terapêutico , Infecções Bacterianas/diagnóstico , Biópsia/efeitos adversos , Ciprofloxacina/uso terapêutico , Próstata/patologia , Idoso , Amicacina/farmacologia , Antibacterianos/farmacologia , Antibioticoprofilaxia , Bactérias/enzimologia , Bactérias/isolamento & purificação , Infecções Bacterianas/etiologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Fluoroquinolonas/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reto/microbiologia , Reto/patologia , Estudos Retrospectivos , Fatores de Risco , Ultrassonografia de Intervenção , beta-Lactamases/metabolismo
8.
J Korean Med Sci ; 33(51): e325, 2018 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-30546281

RESUMO

BACKGROUND: To evaluate survival outcomes and prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who received sunitinib (SU) and pazopanib (PZ) as first-line therapy in real-world Korean clinical practice. METHODS: Data of 554 patients with mRCC who received SU or PZ at eight institutions between 2012 and 2016 were retrospectively reviewed. Based on the targeted therapy, the patients were divided into SU (n = 293) or PZ (n = 261) groups, and the clinicopathological variables and survival rates of the two groups were compared. A multivariable Cox proportional hazard model was used to determine the prognostic factors for OS. RESULTS: The median follow-up was 16.4 months (interquartile range, 8.3-31.3). Patients in the PZ group were older, and no significant difference was observed in the performance status (PS) between the two groups. In the SU group, the dose reduction rate was higher and the incidence of grade 3 toxicity was more frequent. The objective response rates were comparable between the two groups (SU, 32.1% vs. PZ, 36.4%). OS did not differ significantly between the two groups (SU, 36.5 months vs. PZ, 40.2 months; log-rank, P = 0.955). Body mass index, Eastern Cooperative Oncology Group PS > 2, synchronous metastasis, poor Heng risk criteria, and liver and bone metastases were associated with a shorter OS. CONCLUSION: Our real-world data of Korean patients with mRCC suggested that SU and PZ had similar efficacies as first-line therapy for mRCC. However, PZ was better tolerated than SU in Korean patients.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Sunitinibe/uso terapêutico , Idoso , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Indazóis , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
9.
Int J Urol ; 25(5): 414-419, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29478297

RESUMO

OBJECTIVES: To evaluate the surgical feasibility of laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of large pheochromocytomas, and to identify the preoperative risk factors for intraoperative hypertension. METHODS: We retrospectively reviewed 51 patients who underwent laparoscopic adrenalectomy using the lateral retroperitoneal approach for the treatment of pheochromocytomas. Patient characteristics and perioperative outcomes were analyzed and compared between the two study groups based on tumor size: group A (n = 27, ≤6 cm) and group B (n = 24, ˃6 cm). RESULTS: There was no significant difference in preoperative characteristics between the two groups except for tumor size (P = 0.001) and urinary metanephrine (P = 0.011). Group B patients required longer operating time (P = 0.008), had a greater estimated blood loss (P = 0.001) and hemoglobin change (P = 0.002). However, no significant differences were observed in perioperative complications and mortality. Multivariate analysis showed that symptomatic pheochromocytomas (P = 0.004) and tumor size (P = 0.007) were significant risk factors for intraoperative hypertension. CONCLUSIONS: Laparoscopic adrenalectomy using the lateral retroperitoneal approach for pheochromocytomas can be regarded as a treatment option, even for tumors measuring >6 cm. Symptomatic pheochromocytomas and large tumor size seem to represent risk factors for intraoperative hypertension.


Assuntos
Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/efeitos adversos , Adrenalectomia/métodos , Hipertensão/etiologia , Laparoscopia/efeitos adversos , Feocromocitoma/cirurgia , Adulto , Feminino , Humanos , Complicações Intraoperatórias , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Duração da Cirurgia , Assistência Perioperatória , Complicações Pós-Operatórias , República da Coreia , Espaço Retroperitoneal/cirurgia , Estudos Retrospectivos , Fatores de Risco
10.
J Urol ; 197(4): 1048-1053, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27916712

RESUMO

PURPOSE: In prostate cancer ductal adenocarcinoma is mixed with the usual acinar adenocarcinoma. However, to our knowledge whether the proportion of the ductal component affects oncologic outcomes is currently unknown. We investigated whether the proportion of the ductal component predicts oncologic outcomes in ductal adenocarcinoma. MATERIALS AND METHODS: We retrospectively reviewed clinical data on 3,038 patients with prostate cancer who underwent radical prostatectomy at our institution between 2005 and 2014. We excluded patients who received neoadjuvant or adjuvant treatment. Patients were stratified based on the proportion of the ductal component. We compared the probability of biochemical recurrence between groups and investigated how the proportion of the ductal component influences biochemical recurrence using Kaplan-Meier estimates and Cox regression models, respectively. RESULTS: Of 2,648 patients 101 (3.8%) had ductal adenocarcinoma and 2,547 (96.2%) had acinar adenocarcinoma. Freedom from biochemical recurrence in patients with ductal adenocarcinoma was significantly lower than in those with acinar adenocarcinoma (p <0.001). When ductal cases were stratified by the proportion of the ductal component, freedom from biochemical recurrence in the high ductal component group was significantly lower compared to that in the low ductal component group (30% or greater vs less than 30%, p = 0.023). On univariate and multivariate Cox regression analyses, a high ductal component was a significant predictor of biochemical recurrence (p <0.001). CONCLUSIONS: The prognosis for ductal adenocarcinoma can be stratified by the proportion of the ductal component. This marker could potentially be used as a surrogate for poor prognosis or as a determinant for adjuvant therapy.


Assuntos
Adenocarcinoma/patologia , Neoplasias da Próstata/patologia , Adenocarcinoma/cirurgia , Idoso , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata , Prostatectomia , Neoplasias da Próstata/cirurgia , Estudos Retrospectivos
11.
BMC Urol ; 17(1): 37, 2017 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-28549474

RESUMO

BACKGROUND: The most common metastatic sites of prostate cancer are the lymph nodes and bone. Ureteral metastasis from prostate cancer is very unusual and only a few cases have been reported. CASE PRESENTATION: We describe a 76-year-old male with ureteral metastasis of prostate cancer along with a review of the literature. Initially, based on the diagnostic evaluation, urothelial cell carcinoma of the left distal ureter was suspected. Nephroureterectomy with bladder cuff excision was performed. The final pathologic diagnosis was prostate cancer metastatic to the ureter. CONCLUSION: Although rare and the mechanistic link between prostate cancer and distant ureteral metastasis has not been clarified on a clinical basis, this would be included in the differential diagnosis of ureteral lesions in patients with a history of prostate cancer. It is important to recognize this unusual manifestation so that timely appropriate treatment can be initiated.


Assuntos
Carcinoma de Células de Transição/secundário , Neoplasias da Próstata/patologia , Neoplasias Ureterais/secundário , Idoso , Humanos , Masculino
12.
Mass Spectrom Rev ; 34(2): 94-115, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24863621

RESUMO

Insights on mechanisms for the generation of gas-phase peptide ions and their dissociation in matrix-assisted laser desorption ionization (MALDI) gained from the kinetic and ion yield studies are presented. Even though the time-resolved photodissociation technique was initially used to determine the dissociation kinetics of peptide ions and their effective temperature, it was replaced by a simpler method utilizing dissociation yields from in-source decay (ISD) and post-source decay (PSD). The ion yields for a matrix and a peptide were measured by repeatedly irradiating a region on a sample and collecting ion signals until the sample in the region was completely depleted. Matrix- and peptide-derived gas-phase cations were found to be generated by pre-formed ion emission or by ion-pair emission followed by anion loss, but not by laser-induced ionization. The total number of ions, that is, matrix plus peptide, was found to be equal to the number of ions emitted from a pure matrix. A matrix plume was found to cool as it expanded, from around 800-1,000 K to 400-500 K. Dissociation of peptide ions along b/y channels was found to occur statistically, that is, following RRKM behavior. Small critical energy (E0 = 0.6-0.7 eV) and highly negative critical entropy (ΔS(‡) = -30 to -25 eu) suggested that the transition structure was stabilized by multiple intramolecular interactions.


Assuntos
Gases/análise , Íons/química , Peptídeos/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Gases/química , Humanos , Cinética , Peptídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Temperatura , Termodinâmica
13.
Rapid Commun Mass Spectrom ; 30(3): 386-92, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26754131

RESUMO

RATIONALE: In analyte profiling by matrix-assisted laser desorption/ionization (MALDI), drawing a quantitative profile map is an outstanding problem. Recently, we developed a method to quantify an analyte by MALDI, which is needed to solve the problem. Another requirement for quantitative profiling is the quantitative sample-to-matrix analyte transfer, which is investigated in this work. METHODS: MALDI-time-of-flight (TOF) spectra were acquired for samples produced by two methods. In one, a sample solution containing a matrix and an analyte was loaded with a pipet and dried. In the other, a sample was prepared by a consecutive process, i.e., loading-drying of an analyte solution followed by that of a matrix solution. Two different micro-spotters were used in the second method. Various mixtures of organic solvents with water were used to prepare matrix solutions. RESULTS: The organic solvent, matrix, and analyte used in the study did not affect the analyte transfer efficiency, whereas it improved as the water content in the solvent increased. It also improved as the liquid droplet emitted by a micro-spotter got larger. Use of a more polar solvent or a larger droplet increases the contact time between a solution droplet and the sample surface, which seems to be responsible for the improvement in the transfer efficiency. CONCLUSIONS: Sample-to-matrix analyte transfer occurred efficiently when polar solvents and/or large liquid droplets were used to produce solid samples for MALDI profiling with a micro-spotter. A long contact time between the sample surface and a matrix solution droplet is one of the requirements for quantitative profiling. Copyright © 2015 John Wiley & Sons, Ltd.


Assuntos
Solventes/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
14.
Nanomedicine ; 12(3): 655-664, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26586551

RESUMO

Exosomes have recently come into focus as "natural nanoparticles" for use as drug delivery vehicles. Our objective was to assess the feasibility of an exosome-based drug delivery platform for a potent chemotherapeutic agent, paclitaxel (PTX), to treat MDR cancer. Herein, we developed different methods of loading exosomes released by macrophages with PTX (exoPTX), and characterized their size, stability, drug release, and in vitro antitumor efficacy. Reformation of the exosomal membrane upon sonication resulted in high loading efficiency and sustained drug release. Importantly, incorporation of PTX into exosomes increased cytotoxicity more than 50 times in drug resistant MDCKMDR1 (Pgp+) cells. Next, our studies demonstrated a nearly complete co-localization of airway-delivered exosomes with cancer cells in a model of murine Lewis lung carcinoma pulmonary metastases, and a potent anticancer effect in this mouse model. We conclude that exoPTX holds significant potential for the delivery of various chemotherapeutics to treat drug resistant cancers. FROM THE CLINICAL EDITOR: Exosomes are membrane-derived natural vesicles of ~40 - 200 nm size. They have been under extensive research as novel drug delivery vehicles. In this article, the authors developed exosome-based system to carry formulation of PTX and showed efficacy in the treatment of multi-drug resistant cancer cells. This novel system may be further developed to carry other chemotherapeutic agents in the future.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Portadores de Fármacos/química , Exossomos/química , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Pulmão/efeitos dos fármacos , Paclitaxel/administração & dosagem , Animais , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular , Linhagem Celular Tumoral , Cães , Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Pulmão/patologia , Neoplasias Pulmonares/patologia , Macrófagos/química , Camundongos , Camundongos Endogâmicos C57BL , Paclitaxel/farmacocinética , Paclitaxel/uso terapêutico , Sonicação
15.
Rapid Commun Mass Spectrom ; 29(8): 745-52, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-26406489

RESUMO

RATIONALE: In our previous analysis of the matrix-assisted laser desorption/ionization (MALDI) spectra of peptides, we treated their depth profiles in solid samples as homogeneous. Here, we wanted to determine if the reproducible MALDI spectra and linear calibration curves reported previously would be obtained even when the depth profiles were inhomogeneous. METHODS: We derived a formula relating shot-number-dependent ion abundance data in temperature-controlled MALDI with the analyte depth profile in a solid sample. We prepared samples containing peptides, amino acids, and serotonin in α-cyano-4-hydroxycinnamic acid matrix by vacuum-drying and micro-spotting methods, recorded their MALDI spectra, and analyzed them with the aforementioned formula. RESULTS: For the samples prepared by vacuum-drying, the analyte depth profiles were inhomogeneous and maximized at the sample surface. Although the MALDI spectra changed as the shot continued, their sum over the entire set of spectra acquired from a spot was reproducible. Similarly, a high-quality calibration curve could be obtained with the spectral data summed over the entire set. Depth profiles were homogeneous for samples prepared by micro-spotting. CONCLUSIONS: A method has been developed to obtain a reproducible MALDI spectrum and a linear calibration curve for an analyte with an inhomogeneous depth profile in a solid sample.


Assuntos
Aminoácidos/análise , Peptídeos/análise , Serotonina/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Ácidos Cumáricos/química , Reprodutibilidade dos Testes
16.
J Transl Med ; 12: 154, 2014 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-24885363

RESUMO

BACKGROUND: Telomere dysfunction is important in carcinogenesis, and recently, stathmin and elongation factor 1α (EF1α) were reported to be up-regulated in telomere dysfunctional mice. METHODS: In the present study, the expression levels of stathmin and EF1α in relation to telomere length, telomere dysfunction-induced foci (TIF), γ-H2AX, and p21WAF1/CIP1 expression were assessed in specimens of hepatitis B virus (HBV)-related multistep hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas (HCC). Five normal liver specimens were used as controls. TIF were analyzed by telomere fluorescent in situ hybridization (FISH) combined with immunostaining, while the protein expressions of stathmin, EF1α, γ-H2AX, and p21WAF1/CIP1 were detected by immunohistochemistry. RESULT: The expressions of stathmin and EF1α gradually increased as multistep hepatocarcinogenesis progressed, showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade DNs than normal liver and liver cirrhosis, whereas EF1α mRNA expression did not show such a difference. The protein expressions of stathmin and EF1α were found in DNs of precancerous lesions, whereas they were absent or present at very low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher in high-grade DNs and low-grade DNs than in normal liver (all, P<0.05). EF1α histoscores were higher in high-grade DNs than in normal liver and liver cirrhosis (all, P<0.05). Stathmin mRNA levels and histoscores, as well as EF1α histoscores (but not mRNA levels), were positively correlated with telomere shortening and γ-H2AX labeling index (all, P<0.05). EF1α histoscores were also positively correlated with TIF (P<0.001). Significantly greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade DNs, and HCC, compared to liver cirrhosis (all, P<0.05). p21WAF1/CIP1 labeling index was inversely correlated with TIF, stathmin mRNA level, and EF1α histoscore (all, P<0.05). CONCLUSION: Stathmin and EF1α are suggested to be closely related to telomere dysfunction, DNA damage, and inactivation of p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly, assessment of stathmin and EF1α levels as a reflection of telomere dysfunction may be helpful in evaluating the biological characteristics of precancerous hepatic nodules in hepatitis B viral cirrhotic patients.


Assuntos
Hepatite B/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/metabolismo , Fator 1 de Elongação de Peptídeos/metabolismo , Lesões Pré-Cancerosas/metabolismo , Estatmina/metabolismo , Telômero , Adulto , Feminino , Hepatite B/complicações , Humanos , Cirrose Hepática/etiologia , Cirrose Hepática/genética , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Masculino , Pessoa de Meia-Idade , Lesões Pré-Cancerosas/genética
17.
Rapid Commun Mass Spectrom ; 28(7): 787-92, 2014 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-24573810

RESUMO

RATIONALE: Previously, we reported a method (Anal. Chem. 2012, 84, 10332) for peptide quantification based on matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS). In the method, the peptide-to-matrix ion abundance ratio was utilized. Implementation of the method with a commercial MALDI-TOF can be somewhat inconvenient because matrix-derived ions are routinely deflected away to avoid detector saturation. A solution for this inconvenience is required. METHODS: We installed a detector to acquire the TOF spectrum of the ions thrown away to avoid detector saturation. By sending the matrix- and peptide-derived ions along two different tracks and detecting them with different detectors, the inconvenience mentioned above could be avoided. RESULTS: Excellent linearity of the calibration curves obtained by the dual track TOF spectrometry is demonstrated. The method also allows for the acquisition of the tandem mass spectrum of a selected peptide, which can be useful for its identification. CONCLUSIONS: We devised the dual track MALDI-TOF MS method to avoid detector saturation and demonstrated that the quantification and identification of peptides can be performed simultaneously.


Assuntos
Peptídeos/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massas em Tandem/métodos , Calibragem , Modelos Lineares , Peptídeos/química , Peptídeos/isolamento & purificação , Temperatura
18.
Medicine (Baltimore) ; 103(11): e37525, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489740

RESUMO

To evaluate the technical feasibility of the alternative snare technique using a 0.018-inch guide wire and 5-French (Fr) catheter for double-J ureteral stent (DJUS) removal. In this retrospective study, 11 DJUS were removed in 9 consecutive patients between July 2023 and October 2023. We evaluated patient characteristics, DJUS characteristics, and procedure characteristics. Out of 11 cases, 8 (72.7%) were successful in removing the DJUS using the alternative snare technique without major complications. The average time between DJUS insertion and removal was 47.4 ±â€…50.0 days. The most common DJUS size was an 8-Fr, with proximal tips predominantly in the proximal ureter and renal pelvis. The mean procedure time for successful cases was 15.2 ±â€…16.8 minutes. Three failed cases, attributed to obstructions like debris, were later successfully addressed using the ALN inferior vena cava filter removal kit, forceps, and modified snare technique. The alternative snare technique using a 0.018-inch guidewire and Fr catheter is safe and effective in cases of DJUS removal.


Assuntos
Ureter , Humanos , Ureter/cirurgia , Estudos Retrospectivos , Estudos de Viabilidade , Remoção de Dispositivo/métodos , Catéteres , Stents
19.
Anal Chem ; 85(18): 8796-801, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23971407

RESUMO

We propose to divide matrix suppression in matrix-assisted laser desorption ionization into two parts, normal and anomalous. In quantification of peptides, the normal effect can be accounted for by constructing the calibration curve in the form of peptide-to-matrix ion abundance ratio versus concentration. The anomalous effect forbids reliable quantification and is noticeable when matrix suppression is larger than 70%. With this 70% rule, matrix suppression becomes a guideline for reliable quantification, rather than a nuisance. A peptide in a complex mixture can be quantified even in the presence of large amounts of contaminants, as long as matrix suppression is below 70%. The theoretical basis for the quantification method using a peptide as an internal standard is presented together with its weaknesses. A systematic method to improve quantification of high concentration analytes has also been developed.


Assuntos
Peptídeos/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/normas , Calibragem/normas
20.
J Korean Med Sci ; 28(1): 42-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23341710

RESUMO

Pediatric liver transplantation is the standard of care for treatment of liver failure in children. The aim of this study was to identify the characteristics of pediatric liver transplantation in centers located in Korea and determine factors that influence outcomes. This retrospective study was performed using data from between 1988 and 2010 and included all recipients 18 yr old and younger who underwent pediatric liver transplantation in Korea during that period. Our data sources were hospital medical records and the outcome measure was overall patient survival. Univariate and multivariate statistical analyses were undertaken using the Cox proportional hazards model. Five hundred and thirty-four pediatric liver transplantations were performed in 502 children. Median age and average pediatric end-stage liver disease (PELD) score were 20 months and 18 point, respectively. Biliary atresia (57.7%, 308/534) was the most common cause of liver disease. Eighty-two (15.3%) were deceased donor liver transplantations and 454 (84.7%) were living donor liver transplantations. Retransplantation was performed in 32 cases (6%). Overall, 1-, 5-, and 10-yr patient survival rates were 87.8%, 82.2%, and 78.1%, respectively. In multivariate analysis, independent significant predictors of poor patient survival were chronic rejection and retransplantation. This study presents the epidemiologic data for nearly all pediatric liver transplantation in Korea and shows that the independent prognostic factors in patient survival are chronic rejection and retransplantation.


Assuntos
Doença Hepática Terminal/terapia , Transplante de Fígado , Adolescente , Atresia Biliar/epidemiologia , Criança , Pré-Escolar , Doença Hepática Terminal/epidemiologia , Doença Hepática Terminal/mortalidade , Feminino , Sobrevivência de Enxerto , Humanos , Lactente , Masculino , Prognóstico , Modelos de Riscos Proporcionais , República da Coreia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento
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