RESUMEN
Carbonized polymer dots (CPDs) have received tremendous attention during the last decade due to their excellent fluorescent properties and catalytic performance. Doping CPDs with transition metal atoms accelerates the local electron flow in CPDs and improves the fluorescent properties and catalytic performance of the CPDs. However, the binding sites and the formation mechanisms of the transition-metal-atom-doped CPDs remain inconclusive. In this work, Mn2+ -ion-doped CPDs (Mn-CPDs) are synthesized by the hydrothermal method. The Mn2+ ions form MnO bonds that bridge the sp2 domains of carbon cores and increases the effective sp2 domains in the Mn-CPDs, which redshifts the fluorescence emission peak of the Mn-CPDs slightly. The Mn2+ ions form covalent bonds in the CPDs and remedy the oxygen vacancies of the CPDs, which cuts off the non-radiative-recombination process of the Mn-CPDs and increases the quantum yield of the Mn-CPDs to 70%. Furthermore, the MnO bonds accelerate the electron flow between adjacent sp2 domains and enhances the electron transport in the Mn-CPDs. Thus, the Mn-CPDs demonstrate excellent catalytic performance to activate hydrogen peroxide (H2 O2 ) and produce hydroxyl radicals (â¢OH) to degrade methylene blue (MB) and rhodamine B (RhB).
Asunto(s)
Polímeros , Puntos Cuánticos , Carbono/química , Transporte de Electrón , Fluorescencia , Polímeros/química , Puntos Cuánticos/químicaRESUMEN
The study focused on the performance of ultrasound imaging in detecting fetal spinal deformities. First, the double emulsification method and the carbodiimide method were used to prepare the target Au-loaded nanorod phase-change nano-level contrast agent-PLGA-Au-PFH-NPs. After being characterized for physical and chemical properties, it was used in ultrasound imaging diagnosis. The results showed that the prepared PLGA-Au-PFH-NPs solution was a milky white suspension, the particle size detected by the laser particle sizer was (376.17±20.74) nm, and the Zeta potential was (-4.82±2.88) mV. Under the light microscope, it showed a spherical shape, uniform size distribution, and a very smooth surface. The encapsulation rate measured by the UV spectrophotometer was (80.63±4.82) %, and there was no significant difference in cell survival rate between different concentrations (P>0.05). Prenatal ultrasound in the observation group accurately diagnosed 10 cases with spinal deformities, and the diagnostic accuracy rate was 50%, including 5 cases of meningocele, 3 cases of invisible spina bifida, 1 case of myelomeningocele, and 1 case of hemivertebrae. In the control group, 7 cases were diagnosed correctly by conventional ultrasound, and the diagnosis accuracy rate was 35%, including 3 cases of meningocele, 3 cases of invisible spina bifida, and 1 case of hemivertebra. The diagnostic accuracy of the observation group was higher than that of the control group, and the difference was statistically significant (P<0.05). In conclusion, the prepared PLGA-Au-PFH-NPs had good physical and chemical properties. Ultrasound imaging based on the PLGA-Au-PFH-NPs had high accuracy in diagnosing fetal spinal deformities. To a certain extent, it provides a basis for clinical diagnosis of fetal spinal abnormality and some new ideas for ultrasound imaging diagnosis.
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Meningocele , Nanopartículas , Humanos , Ácido Láctico/química , Nanopartículas/química , Tamaño de la Partícula , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ultrasonografía/métodosRESUMEN
Hepatocellular carcinoma (HCC) with metastatic disease is associated with a low survival in clinical practice. Many curative options including liver resection, transplantation, and thermal ablation are effective in local but limited for patients with distant metastasis. In this study, the efficacy, specificity, and safety of P-selectin targeted delivery and microwave (MW) responsive drug release is investigated for development of HCC therapy. By encapsulating doxorubicin (DOX) and MW sensitizer (1-butyl-3-methylimidazolium-l-lactate, BML) into fucoidan conjugated liposomal nanoparticles (TBP@DOX), specific accumulation and prominent release of DOX in orthotopic HCC and lung metastasis are achieved with adjuvant MW exposure. This results in orthotopic HCC growth inhibition that is not only 1.95-fold higher than found for nontargeted BP@DOX and 1.6-fold higher than nonstimuli responsive TP@DOX but is also equivalent to treatment with free DOX at a 10-fold higher dose. Furthermore, the optimum anticancer efficacy against distant lung metastasis and effective prevention of widespread dissemination with a prolonged survival is described. In addition, no adverse metabolic events are identified using the TBP@DOX nanodelivery system despite these events being commonly observed with traditional DOX chemotherapy. Therefore, administering TBP@DOX with MW exposure could potentially enhance the therapeutic efficacy of thermal-chemotherapy of HCC, especially those in the advanced stages.
Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Selectina-P/antagonistas & inhibidores , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Doxorrubicina , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Humanos , Lactatos/química , Lactatos/farmacología , Liposomas/química , Liposomas/farmacología , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/secundario , Microondas , Nanopartículas/química , Metástasis de la Neoplasia , Selectina-P/químicaRESUMEN
BACKGROUND: Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy. RESULTS: The as-made NaCl-DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl-DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect. CONCLUSIONS: This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.
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Antibióticos Antineoplásicos/uso terapéutico , Calcio/metabolismo , Doxorrubicina/uso terapéutico , Hipertermia Inducida/métodos , Nanopartículas/uso terapéutico , Neoplasias/terapia , Animales , Femenino , Células Hep G2 , Humanos , Ratones Desnudos , Microondas , Neoplasias/metabolismo , Neoplasias/patología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/uso terapéuticoRESUMEN
The study used use bimolecular marking methods to evaluate the lignans of Magnolia officinalis and M. officinalis var. biloba. First, we compare the chemical constituents between M. officinalis and M. officinalis var.biloba. There were significant differences in concentration of magnolignan I between leaves of these two varieties. Then we further select the p-hydroxyphenyl lignin to mining the key enzyme genes of biosynthesis from Magnolia transcriptome, and screened an encoding cinnamyl alcohol dehydrogease gene as the candidate marker of bimolecular marking methods of Magnolia quality by comparing of the expression level and structure variation in homologous gene between M. officinalis and M. officinalis var.biloba. The established method provides the technical support for bimolecular marking methods of Magnolia quality evaluation.
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Oxidorreductasas de Alcohol/genética , Magnolia/química , Proteínas de Plantas/genética , Oxidorreductasas de Alcohol/metabolismo , Lignanos/análisis , Lignanos/metabolismo , Lignina/análisis , Lignina/metabolismo , Magnolia/enzimología , Magnolia/genética , Magnolia/metabolismo , Hojas de la Planta/química , Hojas de la Planta/enzimología , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/metabolismo , Control de CalidadRESUMEN
To evaluate the safety and effectiveness of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions, an open, multicenter, controlled, phase â £ clinical trial was conducted in the drug clinical trial centers of 16 domestic hospitals. 2 123 patients from June 10, 2011 to November 29, 2012 were enrolled in the trial. Drug clinical trial was approved by Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital Ethics Committee before implementation. Before the start of trial, subjects were selected according to the research scheme and inclusion criteria, then they would step into the 14 d study after signing Informed Consent Form. All subjects were treated according to the research scheme, evaluated the conditions and filled in CFR sheet, to provide the evaluation data and information on safety and efficacy of Shenbei Guchang capsules. Shenbei Guchang capsules were used to treat diarrhea type irritable bowel syndrome in widely used conditions (2 123 cases), and 2 029 cases of them entered FAS set, cure+markedly effective in 1 921 cases, with a comprehensive curative effect rate of 94.68%; 2 010 cases of them entered PPS set, cure+markedly effective in 1 906 cases, with a comprehensive curative effect rate of 94.83%. The primary symptoms of IBS were abdominal pain and diarrhea. After treatment, both abdominal pain and diarrhea were improved, with significant differences (P<0.000 1). There were significant differences in traditional Chinese medicine symptom scores on both post-treatment day 7 and day 14 as compared with the conditions before treatment (P<0.000 1). 35 cases of adverse events occurred during the trial with an incidence of 1.65%, including 12 cases of drug-related adverse events (adverse reaction) with an incidence of 0.57%, mainly manifested as nausea, abdominal distension and dry mouth, most of which would be spontaneously relieved without any measures. No serious adverse events occurred. The commercially available Shenbei Guchang capsules are proved safe and effective for the treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions (2 123 cases), and can be continued for clinical promotion and application.
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Medicamentos Herbarios Chinos/uso terapéutico , Síndrome del Colon Irritable/tratamiento farmacológico , Cápsulas , Diarrea/tratamiento farmacológico , Humanos , Medicina Tradicional China , Resultado del TratamientoRESUMEN
OBJECTIVE: To explore the effects of atovastatin and tinidazole on atherosclerosis and the levels of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and matrix metalloproteinase-2 (MMP-2) in periodontitis. METHODS: A total of 48 male New Zealand white rabbits were randomly divided into 4 groups (n = 12 each): control group (A), atovastatin group (B), tinidazole group (C) and combination group (D, atovastatin + tinidazole). All groups received interventions according to the experiment design. During Week 1-4, mandibular first premolars were used to establish periodontitis model. For Week 1, adaptive feeding was provided with 50% normal diet + 50% high-fat diet. Then a full high fat-diet was used to establish atherosclerosis model. During Week 16-20, experimental drug intervention was administered twice weekly: group A received the same volume of saline, group B atorvastatin tablets 1.5 mg/kg, group C tinidazole tablets 150 mg/kg and group D atorvastatin tablets 1.5 mg/kg + tinidazole tablets 150 mg/kg. At the end of 20-week intervention, the animals were sacrificed to take vascular and heart tissue samples. Immunohistochemistry and fluorescent polymerase chain reaction (PCR) were employed for quantitative determinations. RESULTS: The positive areas of MMP-2 expression in groups B, C and D were smaller than that of group A respectively (35% ± 17%, 69% ± 5%, 30% ± 7% vs 86% ± 9%, all P < 0.05). And the PCR results showed the levels of TNF-α and IL-1 in group D was the lowest of four groups (all P < 0.05). CONCLUSION: Atovastatin and tinidazole can reduce the expression levels of TNF-α, IL-1 and MMP-2 in the rabbits with atherosclerosis and periodontitis respectively. And the combination of both drugs may achieve a better efficacy.
Asunto(s)
Aterosclerosis/metabolismo , Ácidos Heptanoicos/uso terapéutico , Periodontitis/metabolismo , Pirroles/uso terapéutico , Tinidazol/uso terapéutico , Animales , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Atorvastatina , Interleucina-1/metabolismo , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , Periodontitis/complicaciones , Periodontitis/tratamiento farmacológico , Conejos , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVES: Gene transfer to cardiomyocytes in vivo has received much research attention in the last decade but remains a substantial hurdle. Gene transfer using ultrasound-targeted microbubble destruction is a promising tool for gene therapy. Little data have shown the feasibility and optimization of this method for primary myocardial disease. In this study, we sought to determine the feasibility and efficiency of in vivo gene transfer to the myocardium mediated by ultrasound-targeted microbubble destruction accompanied by polyethylenimine. METHODS: Three plasmids (luciferase reporter, red fluorescent protein reporter, and enhanced green fluorescent protein reporter) were used in this study. The ultrasound parameters were also optimized. A solution containing phosphate-buffered saline, a plasmid, plasmid complex, or polyethylenimine/plasmid, and liposome microbubbles was injected via a tail vein with (study) or without (control) transthoracic ultrasound irradiation. The efficiency of reporter gene transfer was determined by detection of luciferase activity or microscopy, and histologic investigations of the tissue specimens were performed. RESULTS: Ultrasound-targeted microbubble destruction significantly increased luciferase activity in vivo compared to plasmids and microbubbles alone (P < .001). More importantly, the increase in transgene expression was significantly related to ultrasound-targeted microbubble destruction in the presence of polyethylenimine (P < .001). In addition, fluorescein expression was present in all sections that received ultrasound-targeted microbubble destruction. The fluorescent reporter genes and luciferase plasmid all had similar results. Regardless of ultrasound exposure, expression in other organs was close to a background level except for the liver and lung. Hematoxylin-eosin staining showed no notable myocardial injury or death in control and treated mice. CONCLUSIONS: An atraumatic targeted gene delivery technique based on ultrasound-targeted microbubble destruction and polyethylenimine has been developed to transfect cardiomyocytes in vivo. If a suitable target gene is added, the novel technique could be highly effective in many kinds of heart disease.
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Técnicas de Transferencia de Gen , Microburbujas , Miocitos Cardíacos , Sonicación/métodos , Análisis de Varianza , Animales , Estudios de Factibilidad , Terapia Genética/métodos , Liposomas , Masculino , Ratones , Ratones Endogámicos BALB C , Plásmidos , Polietileneimina/farmacologíaRESUMEN
Aim: This study aimed to develop indocyanine green- and doxorubicin-loaded liposomes (DILPs) as theranostic nanoplatform for the detection of hepatocellular carcinoma (HCC) and as an efficient chemotherapeutic to enhance microwave ablation. Materials & methods: DILPs were synthesized and thoroughly characterized. Biocompatibility, tumor uptake and accumulation, and synergistic ablation-chemotherapeutic efficiency were systematically explored in them. In addition, human HCC surgical samples were used to test the affinity of DILPs for HCC. Results: The combination of microwave ablation and DILPs enhanced the ablation efficiency of HCC with apparent tumor inhibition. DILPs exhibited excellent diagnostic ability and could detect 2.5-mm HCC lesions via optoacoustic tomography imaging. DILPs had better affinity for human HCC surgical samples compared with normal liver tissue. Conclusion: Theranostic DILPs could serve as promising nanoparticles for treatment and management of HCC in the clinic.
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Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/terapia , Liposomas/química , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/terapia , Microondas , Animales , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Doxorrubicina/uso terapéutico , Femenino , Células Hep G2 , Humanos , Técnicas In Vitro , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Técnicas Fotoacústicas/métodos , Polietilenglicoles/química , Polietilenglicoles/uso terapéutico , Nanomedicina Teranóstica/métodos , Resultado del TratamientoRESUMEN
With extensive investigations involving liquid metals (LMs), Ga-based LMs have attracted increasing attention from biomedical researchers because of their good biocompatibility, ideal fluidity, and high thermal conductivity. LMs employed in cancer treatment suffer from high surface tension, thereby yielding unstable nanoparticles (NPs). Here, ZrO2 is coated onto LM NPs to form a stable core-shell nanostructure. In particular, LM NPs coated with ZrO2 and modified by PEG (LM@pZrO2 NPs) still maintain favorable flexibility, which is beneficial for cellular uptake. With regard to the photothermal properties of LM, LM@pZrO2 NPs rapidly warm up and emit the requisite amount of heat under NIR laser radiation. It is confirmed that LM@pZrO2 NPs are more effectively internalized by cells and are beneficial for tumor photothermal therapy. This research provides a coating strategy to fabricate a stable and flexible core-shell LM nanostructure, making it a promising vehicle for nanotheranostics.
Asunto(s)
Materiales Biocompatibles Revestidos , Gadolinio , Hipertermia Inducida , Nanopartículas del Metal , Neoplasias Experimentales , Fotoquimioterapia , Polietilenglicoles , Animales , Gadolinio/química , Gadolinio/farmacología , Células Hep G2 , Humanos , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Ratones , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Neoplasias Experimentales/terapia , Polietilenglicoles/química , Polietilenglicoles/farmacología , Circonio/química , Circonio/farmacologíaRESUMEN
OBJECTIVE: The aim of this study was to observe the coexistence of periodontal bacteria DNA (Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella. forsythensis) in coronary atheromatous plaques and subgingival plaques in patients scheduled for coronary artery bypass graft. METHODS: Coronary atheromatous plaque and subgingival plaque samples were obtained from 51 patients and examined by polymerase chain reaction (PCR) technique with specific primers for periodontal bacteria. RESULTS: P. gingivalis (33%), T. forsythensis (31%), P. intermedia (18%) and F. nucleatum (12%) were detected while A. actinomycetemcomitans was negative and not found in coronary atheromatous plaques; T. forsythensis (84%), F. nucleatum (78%), P. intermedia (59%), P. gingivalis (39%) and A. actinomycetemcomitans (22%) were detected in subgingival plaque samples. Coexistence of periodontal bacteria DNA in coronary atheromatous and subgingival plaque samples was evidenced in 32 patients. CONCLUSIONS: The coexistence of T. forsythensis, F. nucleatum, P. intermedia, P. gingivalis in coronary atheromatous plaques and the subgingival plaque samples in CAD patients could suggest a potential role for periodontal pathogenic bacteria in atherosclerosis disease process.
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Enfermedad de la Arteria Coronaria/microbiología , Placa Dental/microbiología , Encía/microbiología , Adulto , Anciano , Bacteroides/aislamiento & purificación , Puente de Arteria Coronaria , Enfermedad de la Arteria Coronaria/cirugía , ADN Bacteriano/análisis , Femenino , Fusobacterium nucleatum/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la PolimerasaRESUMEN
Although microwave (MW) thermal therapy has been widely studied for the treatment of tumors due to its less invasiveness, recurrence of tumors is still observed because of the relatively low bioavailability of MW sensitizers. For enhancing the bioavailability of MW sensitizers, triphenyl phosphate (TPP)-conjugated and doxorubicin (DOX)-loaded porous zirconium metal-organic framework nanocubes (ZrMOF NCs) modified with polyethylene glycol (PEG), ZrMOF-PEG-TPP@DOX NCs, were prepared as a MW sensitizer with mitochondrial-targeting ability. Moreover, the mitochondria are more susceptible to heat than the tumor tissues; this leads to improved tumor cell apoptosis. The results of this study indicate that ZrMOF NCs exhibit excellent heating effects due to the increased collisions of ions in the micropores of ZrMOFs under MW irradiation. In addition, ZrMOF-PEG-TPP@DOX NCs show preferential aggregation in the mitochondria, confirmed by confocal microscopy images. In vivo MW thermal therapeutic efficacy of ZrMOF-PEG-TPP@DOX NCs + MW is also better without recurrence during treatment than that of ZrMOF-PEG@DOX NCs + MW at a similar thermal therapeutic temperature; this reveals that the mitochondrial-targeting strategy can enhance the MW thermal therapeutic efficacy. This study provides a new biosafe MW sensitizer with mitochondrial-targeting ability for enhancing the efficacy of MW thermal therapy against tumors.
Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Doxorrubicina/administración & dosificación , Portadores de Fármacos/química , Hipertermia Inducida/métodos , Estructuras Metalorgánicas/química , Neoplasias/terapia , Circonio/química , Animales , Antibióticos Antineoplásicos/uso terapéutico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Doxorrubicina/uso terapéutico , Sistemas de Liberación de Medicamentos , Ratones , Microondas , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Nanopartículas/química , Neoplasias/metabolismo , Neoplasias/patología , Organofosfatos/química , Polietilenglicoles/químicaRESUMEN
Microwave ablation (MWA) is a promising minimally invasive therapy that has been widely used to treat hepatocellular carcinoma (HCC). However, the efficiency of MWA in treating HCC is evidently limited by the incomplete ablation of large tumors and tumors in high-risk locations. Here, we report the value of using liposomes packed with sodium chloride (NaCl-LPs) as effective thermo-seeds for MWA of HCC. The prepared liposomes exhibited excellent heat conversion ability by showing a more rapid temperature increase than free NaCl medium, blank liposomes or water under microwave irradiation. The high efficiency of this new microwave sensitization strategy was fully demonstrated in vitro in subcutaneous and orthotopic tumors. The results showed that MWA combined with NaCl-LPs clearly enhanced the ablation efficiency, leading to apparent tumor inhibition and low recurrence. What's more, we verified the susceptibility of NaCl-LPs on orthotopic tumors. Based on the unique properties of NaCl-LPs, sublethal MWA was used to mimic the transitional zone, and large-scale necrosis was observed in tumors combined with NaCl-LPs. In addition, HE staining and blood hematology analysis revealed no noticeable toxicity of NaCl-LPs in vivo, which confirmed that NaCl-LPs possessed good biocompatibility. CONCLUSION: The effective nanoparticles could play a valuable role in enhancing the thermo-sensitizing effect of MWA for achieving better therapeutic efficacy.
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Carcinoma Hepatocelular/terapia , Liposomas , Neoplasias Hepáticas/terapia , Microondas , Cloruro de Sodio/administración & dosificación , Técnicas de Ablación , Animales , Femenino , Células Hep G2 , Humanos , Ratones Endogámicos BALB C , Neoplasias Experimentales/terapia , Resultado del TratamientoRESUMEN
Although nanoparticle-based photothermal therapy (PTT) has been intensively investigated recently, its comparative efficiency with any clinical cancer treatments has been rarely explored. Herein for the first time we report a systematic comparative study of clinical iodine-125 (125 I) interstitial brachytherapy (IBT-125-I) and interventional PTT (IPTT) in an orthotopic xenograft model of human pancreatic cancer. IPTT, based on the nanoparticles composing of anti-urokinase plasminogen activator receptor (uPAR) antibody, polyethylene glycol (PEG), and indocyanine green (ICG) modified gold nanoshells (hereinafter uIGNs), is directly applied to local pancreatic tumor deep in the abdomen. In comparison to IBT-125-I, a 25% higher median survival rate of IPTT with complete ablation by one-time intervention has been achieved. The IPTT could also inhibit pancreatic tumor metastasis which can be harnessed for effective cancer immunotherapy. All results show that this IPTT is a safe and radical treatment for eradicating tumor cells, and may benefit future clinical pancreatic cancer patients.
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Neoplasias Pancreáticas , Línea Celular Tumoral , Oro , Humanos , Verde de Indocianina , Nanocáscaras , Fototerapia , PolietilenglicolesRESUMEN
To examine the potential of high density lipoproteins (HDL) to ameliorate atherosclerotic plaques in vivo, we examined the ability of native HDL, lipid-free HDL apolipoproteins (apo HDL), cholesterol-free discoidal reconstituted HDL (R-HDL) comprised of apo HDL and phosphatidylcholine (PC) and PC liposomes to release cholesterol from cholesterol-rich insoluble components of plaques (ICP) isolated from atherosclerotic human aorta. Isolated ICP had a free cholesterol (FC) to phospholipid (PL) mass ratio (0.8-3.1) and a sphingomyelin (SPM) to PC mass ratio (1.2-4.2) that exceeded those of plasma membranes of cultured cells. Surprisingly, native HDL and its apolipoproteins were not able to release cholesterol from ICP. However, R-HDL and PC liposomes were effectively released cholesterol from ICP. The release of ICP cholesterol by R-HDL was dose-dependent and accompanied by the transfer of > 8 x more PC in the reverse direction (i.e., from R-HDL to ICP), resulting in a marked enrichment of ICP with PC. Compared to R-HDL, PC liposomes were significantly less effective in releasing cholesterol from ICP but were somewhat more effective in enriching ICP with PC. Native HDL was minimally effective in enriching ICP with PC, but became effective after prior in vitro enrichment of HDL with PC from multilamellar PC liposomes. The enrichment of ICP with PC resulted in the dissolution of cholesterol crystals on ICP and allowed the removal of ICP cholesterol by apo HDL and plasma. Our study revealed that the removal of cholesterol from ICP in vivo will be possible through a change in the level, composition, and physical state of ICP lipids mediated by PC-enriched HDL.
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Apolipoproteínas/fisiología , Arteriosclerosis/metabolismo , Colesterol/metabolismo , Lipoproteínas HDL/fisiología , Fosfatidilcolinas/metabolismo , Aorta/efectos de los fármacos , Aorta/patología , Apolipoproteínas/farmacología , Arteriosclerosis/patología , Membrana Celular/metabolismo , Células Cultivadas , Humanos , Lipoproteínas HDL/farmacología , Liposomas , Esfingomielina Fosfodiesterasa/farmacología , Esfingomielinas/metabolismoRESUMEN
Data on long-term survival and prognostic significance of demographic factors and adverse events (AEs) associated with sorafenib, an orally administered multikinase inhibitor in Chinese population with advanced renal cell carcinoma (RCC) are limited. Outcome data from adult patients (n = 256) with advanced RCC who received sorafenib (400 mg twice daily) either as first-line or second-line therapy between April 2006 and May 2013 were analyzed retrospectively. The primary endpoint was median overall survival (OS), determined to be 22.2 (95% CI: 17.1-27.4) months, and the secondary endpoint was overall median progression-free survival (PFS), determined to be 13.6 (95% CI: 10.7-16.4) months at a median follow-up time of 61.8 (95% CI: 16.2-97.4) months. Analysis of the incidence of AEs revealed the most common side effect as hand-foot skin reactions (60.5%) followed by diarrhea (38.7%), fatigue (35.5%), alopecia (34.0%), rash (24.6%), hypertension (21.5%) and gingival hemorrhage (21.1%). Multivariate regression analysis revealed older age (≥ 58 years), lower Memorial Sloan-Kettering Cancer Center score, time from nephrectomy to sorafenib treatment, number of metastatic tumors and best response as significant and independent demographic predictors for improved PFS and/or OS (p ≤ 0.05). Alopecia was identified as a significant and independent predictor of increased OS, whereas vomiting and weight loss were identified as significant predictors of decreased OS (p ≤ 0.05). Sorafenib significantly improved OS and PFS in Chinese patients with advanced RCC. Considering the identified significant prognostic demographic factors along with the advocated prognostic manageable AEs while identifying treatment strategy may help clinicians select the best treatment modality and better predict survival in these patients.
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Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Carcinoma de Células Renales/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Pronóstico , Estudios Retrospectivos , Sorafenib , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
A minimally invasive, highly efficient and versatile strategy is proposed for localized tumor regression by developing a smart injectable liquid-solid phase-transformation organic-inorganic hybrid composite material, i.e., magnetic-Fe-powder-dispersed PLGA (Fe/PLGA) implants for magnetic hyperthermia therapy of cancer.
Asunto(s)
Adenocarcinoma/terapia , Hipertermia Inducida , Campos Magnéticos , Nanopartículas de Magnetita/administración & dosificación , Técnicas de Ablación/instrumentación , Técnicas de Ablación/métodos , Adenocarcinoma/patología , Animales , Humanos , Hipertermia Inducida/instrumentación , Hipertermia Inducida/métodos , Ácido Láctico/administración & dosificación , Ácido Láctico/química , Células MCF-7 , Nanopartículas de Magnetita/química , Ratones Desnudos , Microscopía Electrónica de Transmisión , Necrosis/patología , Trasplante de Neoplasias , Transición de Fase , Ácido Poliglicólico/administración & dosificación , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polvos , Cloruro de Sodio/química , Temperatura , Carga Tumoral , UltrasonografíaRESUMEN
Apoptosis is a physiologically essential mechanism of cell and plays an important role in reducing the development and progression of tumors. The appealing strategy for cancer therapy is to target the lesions that induce apoptosis in cancer cells. Survivin, the smallest member of the mammalian inhibitors of the apoptosis protein family, is upregulated in various malignancies to protect cells from apoptosis. Survivin knockdown could induce cancer cell apoptosis and inhibit tumor-angiogenesis. Survivin expression would be silenced by microRNA (miRNA)-mediated RNA interference. However, noninvasive and tissue-specific gene delivery techniques remain absent recently and the utilizations of miRNA expression vectors have been limited by inefficient delivery technique, especially in vivo. On the other hand, safe and promising technologies of gene transfection would be valuable in clinical gene therapy. Successful treatment of gene transfer method would lead to a new and readily available approach in the anticancer research. Sonoporation is an alternative technique of gene delivery that uses ultrasound targeted microbubble destruction to create pores in the cell membrane. Based on our previous studies, in this article, we postulated that the transfection of miRNA could be mediated by the combination of sonoporation and polyethylenimine (PEI) which was one of the most effective poly-cationic gene vectors and enhance the endocytosis of plasmids DNA and hypothesized that the gene silencing and apoptosis induction with miRNA targeting human Survivin would be improved by this novel technique. In our opinion, this novel combination of sonoporation and PEI could enhance targeted gene delivery effectively and might be a feasible, novel candidate for gene therapy.