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1.
Proc Natl Acad Sci U S A ; 121(5): e2318265121, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38261618

RESUMO

Surgical resections of solid tumors guided by visual inspection of tumor margins have been performed for over a century to treat cancer. Near-infrared (NIR) fluorescence labeling/imaging of tumor in the NIR-I (800 to 900 nm) range with systemically administrated fluorophore/tumor-targeting antibody conjugates have been introduced to improve tumor margin delineation, tumor removal accuracy, and patient survival. Here, we show Au25 molecular clusters functionalized with phosphorylcholine ligands (AuPC, ~2 nm in size) as a preclinical intratumorally injectable agent for NIR-II/SWIR (1,000 to 3,000 nm) fluorescence imaging-guided tumor resection. The AuPC clusters were found to be uniformly distributed in the 4T1 murine breast cancer tumor upon intratumor (i.t.) injection. The phosphocholine coating afforded highly stealth clusters, allowing a high percentage of AuPC to fill the tumor interstitial fluid space homogeneously. Intra-operative surgical navigation guided by imaging of the NIR-II fluorescence of AuPC allowed for complete and non-excessive tumor resection. The AuPC in tumors were also employed as a photothermal therapy (PTT) agent to uniformly heat up and eradicate tumors. Further, we performed in vivo NIR-IIb (1,500 to 1,700 nm) molecular imaging of the treated tumor using a quantum dot-Annexin V (QD-P3-Anx V) conjugate, revealing cancer cell apoptosis following PTT. The therapeutic functionalities of AuPC clusters combined with rapid renal excretion, high biocompatibility, and safety make them promising for clinical translation.


Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Humanos , Animais , Camundongos , Feminino , Imagem Óptica , Anexina A5 , Apoptose , Ouro
2.
Proc Natl Acad Sci U S A ; 119(15): e2123111119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35380898

RESUMO

In vivo fluorescence/luminescence imaging in the near-infrared-IIb (NIR-IIb, 1,500 to 1,700 nm) window under <1,000 nm excitation can afford subcentimeter imaging depth without any tissue autofluorescence, promising high-precision intraoperative navigation in the clinic. Here, we developed a compact imager for concurrent visible photographic and NIR-II (1,000 to 3,000 nm) fluorescence imaging for preclinical image-guided surgery. Biocompatible erbium-based rare-earth nanoparticles (ErNPs) with bright down-conversion luminescence in the NIR-IIb window were conjugated to TRC105 antibody for molecular imaging of CD105 angiogenesis markers in 4T1 murine breast tumors. Under a ∼940 ± 38 nm light-emitting diode (LED) excitation, NIR-IIb imaging of 1,500- to 1,700-nm emission afforded noninvasive tumor­to­normal tissue (T/NT) signal ratios of ∼40 before surgery and an ultrahigh intraoperative tumor-to-muscle (T/M) ratio of ∼300, resolving tumor margin unambiguously without interfering background signal from surrounding healthy tissues. High-resolution imaging resolved small numbers of residual cancer cells during surgery, allowing thorough and nonexcessive tumor removal at the few-cell level. NIR-IIb molecular imaging afforded 10-times-higher and 100-times-higher T/NT and T/M ratios, respectively, than imaging with IRDye800CW-TRC105 in the ∼900- to 1,300-nm range. The vastly improved resolution of tumor margin and diminished background open a paradigm of molecular imaging-guided surgery.


Assuntos
Érbio , Neoplasias Mamárias Experimentais , Nanopartículas Metálicas , Imagem Óptica , Espectroscopia de Luz Próxima ao Infravermelho , Cirurgia Assistida por Computador , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Fluorescência , Corantes Fluorescentes/química , Neoplasias Mamárias Experimentais/diagnóstico por imagem , Neoplasias Mamárias Experimentais/cirurgia , Camundongos , Neoplasia Residual/diagnóstico por imagem , Imagem Óptica/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cirurgia Assistida por Computador/métodos
3.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526701

RESUMO

Noninvasive optical imaging with deep tissue penetration depth and high spatiotemporal resolution is important to longitudinally studying the biology at the single-cell level in live mammals, but has been challenging due to light scattering. Here, we developed near-infrared II (NIR-II) (1,000 to 1,700 nm) structured-illumination light-sheet microscopy (NIR-II SIM) with ultralong excitation and emission wavelengths up to ∼1,540 and ∼1,700 nm, respectively, suppressing light scattering to afford large volumetric three-dimensional (3D) imaging of tissues with deep-axial penetration depths. Integrating structured illumination into NIR-II light-sheet microscopy further diminished background and improved spatial resolution by approximately twofold. In vivo oblique NIR-II SIM was performed noninvasively for 3D volumetric multiplexed molecular imaging of the CT26 tumor microenvironment in mice, longitudinally mapping out CD4, CD8, and OX40 at the single-cell level in response to immunotherapy by cytosine-phosphate-guanine (CpG), a Toll-like receptor 9 (TLR-9) agonist combined with OX40 antibody treatment. NIR-II SIM affords an additional tool for noninvasive volumetric molecular imaging of immune cells in live mammals.


Assuntos
Imageamento Tridimensional , Imagem Óptica/métodos , Análise de Célula Única , Receptor Toll-Like 9/isolamento & purificação , Animais , Linhagem Celular Tumoral , Microambiente Celular/genética , Camundongos , Microscopia de Fluorescência/métodos , Receptor Toll-Like 9/genética
4.
Angew Chem Int Ed Engl ; 59(46): 20552-20560, 2020 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-32681553

RESUMO

Most NIR-IIb fluorophores are nanoparticle-based probes with long retention (≈1 month or longer) in the body. Here, we applied a novel cross-linked coating to functionalize core/shell lead sulfide/cadmium sulfide quantum dots (PbS/CdS QDs) emitting at ≈1600 nm. The coating was comprised of an amphiphilic polymer followed by three crosslinked amphiphilic polymeric layers (P3 coating), imparting high biocompatibility and >90 % excretion of QDs within 2 weeks of intravenous administration. The P3 -QDs were conjugated to an engineered anti-CD8 diabody (Cys-diabody) for in vivo molecular imaging of CD8+ cytotoxic T lymphocytes (CTLs) in response to anti-PD-L1 therapy. Two-plex molecular imaging in combination with down-conversion Er nanoparticles (ErNPs) was performed for real-time in vivo monitoring of PD-L1 positive tumor cells and CTLs with cellular resolution by non-invasive NIR-IIb light sheet microscopy. Imaging of angiogenesis in the tumor microenvironment and of lymph nodes deep in the body with a signal-to-background ratio of up to ≈170 was also achieved using P3 -QDs.


Assuntos
Nanopartículas/química , Medicina de Precisão , Antígeno B7-H1/imunologia , Linfócitos T CD8-Positivos/citologia , Corantes Fluorescentes/química , Células HeLa , Humanos , Linfonodos/patologia , Pontos Quânticos/química , Espectroscopia de Luz Próxima ao Infravermelho , Microambiente Tumoral
5.
J Am Chem Soc ; 141(9): 4086-4093, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30699294

RESUMO

A central topic in single-atom catalysis is building strong interactions between single atoms and the support for stabilization. Herein we report the preparation of stabilized single-atom catalysts via a simultaneous self-reduction stabilization process at room temperature using ultrathin two-dimensional Ti3- xC2T yMXene nanosheets characterized by abundant Ti-deficit vacancy defects and a high reducing capability. The single atoms therein form strong metal-carbon bonds with the Ti3- xC2T y support and are therefore stabilized onto the sites previously occupied by Ti. Pt-based single-atom catalyst (SAC) Pt1/Ti3- xC2T y offers a green route to utilizing greenhouse gas CO2, via the formylation of amines, as a C1 source in organic synthesis. DFT calculations reveal that, compared to Pt nanoparticles, the single Pt atoms on Ti3- xC2T y support feature partial positive charges and atomic dispersion, which helps to significantly decrease the adsorption energy and activation energy of silane, CO2, and aniline, thereby boosting catalytic performance. We believe that these results would open up new opportunities for the fabrication of SACs and the applications of MXenes in organic synthesis.

6.
Phys Chem Chem Phys ; 18(46): 31828-31835, 2016 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-27841403

RESUMO

In this study, we report anomalous size-dependent photoluminescence (PL) intensity variation of PbS quantum dots (QDs) with the formation of a thin CdS shell via a microwave-assisted cation exchange approach. Thin shell formation has been established as an effective strategy for increasing the PL of QDs. Nonetheless, herein we observed an unusual PL decrease in ultrasmall QDs upon shell formation. We attempted to understand this abnormal phenomenon from the perspective of trap density variation and the probability of electrons and holes reaching surface defects. To this end, the quantum yield (QY) and PL lifetime (on the ns-µs time scales) of pristine PbS QDs and PbS/CdS core/shell QDs were measured and the radiative and non-radiative recombination rates were derived and compared. Moreover, transient absorption (TA) analysis (on the fs-ns time scale) was performed to better understand exciton dynamics at early times that lead to and affect longer time dynamics and optical properties such as PL. These experimental results, in conjunction with theoretical calculations of electron and hole wave functions, provide a complete picture of the photophysics governing the core/shell system. A model was proposed to explain the size-dependent optical and dynamic properties observed.

7.
Nat Biomed Eng ; 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37620621

RESUMO

Tracking and imaging immune cells in vivo non-invasively would offer insights into the immune responses induced by vaccination. Here we report a cancer vaccine consisting of polymer-coated NaErF4/NaYF4 core-shell down-conversion nanoparticles emitting luminescence in the near-infrared spectral window IIb (1,500-1,700 nm in wavelength) and with surface-conjugated antigen (ovalbumin) and electrostatically complexed adjuvant (class-B cytosine-phosphate-guanine). Whole-body wide-field imaging of the subcutaneously injected vaccine in tumour-bearing mice revealed rapid migration of the nanoparticles to lymph nodes through lymphatic vessels, with two doses of the vaccine leading to the complete eradication of pre-existing tumours and to the prophylactic inhibition of tumour growth. The abundance of antigen-specific CD8+ T lymphocytes in the tumour microenvironment correlated with vaccine efficacy, as we show via continuous-wave imaging and lifetime imaging of two intravenously injected near-infrared-emitting probes (CD8+-T-cell-targeted NaYbF4/NaYF4 nanoparticles and H-2Kb/ovalbumin257-264 tetramer/PbS/CdS quantum dots) excited at different wavelengths, and by volumetrically visualizing the three nanoparticles via light-sheet microscopy with structured illumination. Nanoparticle-based vaccines and imaging probes emitting infrared light may facilitate the design and optimization of immunotherapies.

8.
J Surg Oncol ; 106(3): 311-5, 2012 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-22124972

RESUMO

BACKGROUND AND OBJECTIVES: The aim of this retrospective study is to summarize our improvement of surgical procedures for radical resection of left hilar tumors involving the pulmonary trunk and determine its clinical feasibility. METHODS: From 2001 to 2008, four patients were selected for curative extended resection through multidisciplinary assessment and the pulmonary trunk was reconstructed via cardiopulmonary bypass (CPB). Surgical procedures were performed with posterolateral thoracotomy for two patients and anterolateral thoracotomy for the remaining two. CPB was performed via femoral artery-femoral vein cannulation on one patient and right atrial-aortic cannulation on the other three patients. Polytetrafluoroethylene patch or autologous pericardium was applied for reconstruction in different patients. RESULTS: The duration of the operations ranged from 300 to 440 min and with CPB lasting 35-106 min. Three patients developed non-specific complications with no mortalities and discharged within 12-17 days. One patient had no evidence of recurrence during 50 months follow-up. Three patients died of metastasis 5, 14, and 35 months after surgery. CONCLUSIONS: CPB-supported extended resection of lung malignancies involving the pulmonary trunk is feasible. Left anterolateral thoracotomy through the fourth intercostal space with right atrial-aortic cannulation would be the convenient approach. Survival may be prolonged in some selected patients.


Assuntos
Ponte Cardiopulmonar/métodos , Neoplasias Pulmonares/cirurgia , Artéria Pulmonar/cirurgia , Veias Pulmonares/cirurgia , Adulto , Idoso , Carcinossarcoma/mortalidade , Carcinossarcoma/patologia , Carcinossarcoma/cirurgia , Estudos de Viabilidade , Seguimentos , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Artéria Pulmonar/patologia , Veias Pulmonares/patologia , Estudos Retrospectivos , Rabdomiossarcoma/mortalidade , Rabdomiossarcoma/patologia , Rabdomiossarcoma/cirurgia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/cirurgia , Toracotomia
9.
Thorac Cancer ; 13(15): 2257-2259, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35734847

RESUMO

Lung cancer has become a leading cause of cancer-related deaths. With the conventional use of low-dose spiral computed tomography (CT) in physical examinations, an increasing number of small pulmonary nodules are screened. However, primary pulmonary meningiomas (PPMs) are rarely reported. Here, we report the case of a 64-year-old woman who had a CT scan during physical examination, which revealed three ground-glass-like opacity pulmonary nodules in both lungs. The patient underwent video-assisted thoracoscopic wedge resection of the right upper and lower lobes. Paraffin sections revealed pulmonary meningothelial-like and collagenous nodules in the right upper and lower lobes which stained as follows: EMA+, VIM+, SMA-, S-100-, CD34-, STAT6-, Ki-67+ (2%), and CgA-. Primary pulmonary meningiomas (PPMs) were finally diagnosed. PPM is a kind of rare and benign tumor. Surgery can provide a precise pathological examination, and patients can achieve an excellent prognosis after surgical resection.


Assuntos
Neoplasias Pulmonares , Neoplasias Meníngeas , Meningioma , Nódulos Pulmonares Múltiplos , Neoplasias Primárias Múltiplas , Feminino , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/patologia , Cirurgia Torácica Vídeoassistida
10.
Nat Commun ; 13(1): 5613, 2022 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-36153336

RESUMO

Sentinel lymph node imaging and biopsy is important to clinical assessment of cancer metastasis, and novel non-radioactive lymphographic tracers have been actively pursued over the years. Here, we develop gold molecular clusters (Au25) functionalized by phosphorylcholine (PC) ligands for NIR-II (1000-3000 nm) fluorescence imaging of draining lymph nodes in 4T1 murine breast cancer and CT26 colon cancer tumor mouse models. The Au-phosphorylcholine (Au-PC) probes exhibit 'super-stealth' behavior with little interactions with serum proteins, cells and tissues in vivo, which differs from the indocyanine green (ICG) dye. Subcutaneous injection of Au-PC allows lymph node mapping by NIR-II fluorescence imaging at an optimal time of ~ 0.5 - 1 hour postinjection followed by rapid renal clearance. Preclinical NIR-II fluorescence LN imaging with Au-PC affords high signal to background ratios and high safety and biocompatibility, promising for future clinical translation.


Assuntos
Verde de Indocianina , Neoplasias , Animais , Corantes , Fluorescência , Ouro , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Camundongos , Neoplasias/patologia , Imagem Óptica , Fosforilcolina , Biópsia de Linfonodo Sentinela/métodos
11.
Nat Nanotechnol ; 17(6): 653-660, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35606441

RESUMO

Light scattering by biological tissues sets a limit to the penetration depth of high-resolution optical microscopy imaging of live mammals in vivo. An effective approach to reduce light scattering and increase imaging depth is to extend the excitation and emission wavelengths to the second near-infrared window (NIR-II) at >1,000 nm, also called the short-wavelength infrared window. Here we show biocompatible core-shell lead sulfide/cadmium sulfide quantum dots emitting at ~1,880 nm and superconducting nanowire single-photon detectors for single-photon detection up to 2,000 nm, enabling a one-photon excitation fluorescence imaging window in the 1,700-2,000 nm (NIR-IIc) range with 1,650 nm excitation-the longest one-photon excitation and emission for in vivo mouse imaging so far. Confocal fluorescence imaging in NIR-IIc reached an imaging depth of ~1,100 µm through an intact mouse head, and enabled non-invasive cellular-resolution imaging in the inguinal lymph nodes of mice without any surgery. We achieve in vivo molecular imaging of high endothelial venules with diameters as small as ~6.6 µm, as well as CD169 + macrophages and CD3 + T cells in the lymph nodes, opening the possibility of non-invasive intravital imaging of immune trafficking in lymph nodes at the single-cell/vessel-level longitudinally.


Assuntos
Nanofios , Pontos Quânticos , Animais , Mamíferos , Camundongos , Microscopia de Fluorescência/métodos , Imagem Óptica/métodos , Fótons , Pontos Quânticos/química
12.
Angew Chem Weinheim Bergstr Ger ; 132(46): 20733-20741, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34334834

RESUMO

Most NIR-IIb fluorophores are nanoparticle-based probes with long retention ( ≈ 1 month or longer) in the body. Here, we applied a novel cross-linked coating to functionalize core/shell lead sulfide/cadmium sulfide quantum dots (PbS/CdS QDs) emitting at ≈ 1600 nm. The coating was comprised of an amphiphilic polymer followed by three crosslinked amphiphilic polymeric layers (P3 coating), imparting high biocompatibility and > 90% excretion of QDs within 2 weeks of intravenous administration. The P3-QDs were conjugated to an engineered anti-CD8 diabody (Cys-diabody) for in vivo molecular imaging of CD8 + cytotoxic T lymphocytes (CTLs) in response to anti-PD-L1 therapy. Two-plex molecular imaging in combination with down-conversion Er nanoparticles (ErNPs) was performed for real-time in vivo monitoring of PD-L1 positive tumor cells and CTLs with cellular resolution by non-invasive NIR-IIb light sheet microscopy. Imaging of angiogenesis in the tumor microenvironment and of lymph nodes deep in the body with a signal-to-background ratio of up to ≈ 170 was also achieved using P3-QDs.

13.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 26(6): 1291-4, 2009 Dec.
Artigo em Zh | MEDLINE | ID: mdl-20095489

RESUMO

This study was conducted to modify the method for establishing the model of myocardial infarction by ligation of the left anterior descending branch (LAD) of coronary artery in rats, and then observations on them were made with the use of electrocardiography, heart function exam and histomorphology. 30 adult male inbred strain Wistar rats were randomly divided into two groups: sham group (n = 5) and model group (n = 25). Each rat in the model group underwent a ligation of the left anterior descending branch. Subsequently, the two groups were compared by use of electrocardiography, heart function and histomorphology. The results have demonstrated that, after being improved, the ligation of the left anterior descending branch of coronary artery is a good method to establish the stable model of myocardial infarction. It can be applied to the research in mechanism and treatment of myocardial infarction.


Assuntos
Vasos Coronários/cirurgia , Modelos Animais de Doenças , Infarto do Miocárdio , Animais , Ligadura/métodos , Masculino , Infarto do Miocárdio/etiologia , Distribuição Aleatória , Ratos , Ratos Wistar
14.
ACS Nano ; 13(1): 408-420, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30604607

RESUMO

Developing multifunctional therapeutic and diagnostic (theranostic) nanoplatforms is critical for addressing challenging issues associated with cancers. Here, self-assembled supernanoparticles consisting of superparamagnetic Fe3O4 nanoparticles and photoluminescent PbS/CdS quantum dots whose emission lies within the second biological window (II-BW) are developed. The proposed self-assembled Fe3O4 and PbS/CdS (II-BW) supernanoparticles [SASNs (II-BW)] exhibit outstanding photoluminescence detectable through a tissue as thick as 14 mm, by overcoming severe light extinction and concomitant autofluorescence in II-BW, and significantly enhanced T2 relaxivity (282 mM-1 s-1, ca. 4 times higher than free Fe3O4 nanoparticles) due to largely enhanced magnetic field inhomogeneity. On the other hand, SASNs (II-BW) possess the dual capacity to act as both magnetothermal and photothermal agents, overcoming the main drawbacks of each type of heating separately. When SASNs (II-BW) are exposed to the dual-mode (magnetothermal and photothermal) heating, the thermal energy transfer efficiency is amplified 7-fold compared with magnetic heating alone. These results, in hand with the excellent photo- and colloidal stability, and negligible cytotoxicity, demonstrate the potential use of SASNs (II-BW) for deep-tissue bimodal (magnetic resonance and photoluminescence) in vivo imaging, while simultaneously providing the possibility of SASNs (II-BW)-mediated amplified dual-mode heating treatment for cancer therapy.


Assuntos
Hipertermia Induzida/métodos , Nanopartículas Metálicas/química , Neoplasias Experimentais/diagnóstico por imagem , Animais , Compostos de Cádmio/química , Feminino , Compostos Férricos/química , Células HeLa , Humanos , Chumbo/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Experimentais/terapia , Fototerapia/métodos , Pontos Quânticos/química , Pontos Quânticos/uso terapêutico , Sulfetos/química , Nanomedicina Teranóstica/métodos
15.
Sci Rep ; 7(1): 14741, 2017 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-29116136

RESUMO

PbS based quantum dots (QDs) have been studied in great detail for potential applications in electroluminescent devices operating at wavelengths important for telecommunications (1.3-1.6 µm). Despite the recent advances in field of quantum dot light-emitting diode (QLED), further improvements in near-infrared (NIR) emitting device performance are still necessary for the widespread use and commercialization of NIR emitting QLED technology. Here, we report a high-performance 1.51-µm emitting QLED with inverted organic-inorganic hybrid device architecture and PbS/CdS core-shell structured quantum dots as emitter. The resultant QLEDs show a record device performance for the QLEDs in 1.5 µm emission window, with a maximum radiance of 6.04 Wsr-1 m-2 and peak external quantum efficiency (EQE) of 4.12%, respectively.

16.
Adv Healthc Mater ; 6(4)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28009096

RESUMO

There is an urgent need to develop new diagnosis tools for real in vivo detection of first stages of ischemia for the early treatment of cardiovascular diseases and accidents. However, traditional approaches show low sensitivity and a limited penetration into tissues, so they are only applicable for the detection of surface lesions. Here, it is shown how the superior thermal sensing capabilities of near infrared-emitting quantum dots (NIR-QDs) can be efficiently used for in vivo detection of subcutaneous ischemic tissues. In particular, NIR-QDs make possible ischemia detection by high penetration transient thermometry studies in a murine ischemic hindlimb model. NIR-QDs nanothermometers are able to identify ischemic tissues by means of their faster thermal dynamics. In addition, they have shown to be capable of monitoring both the revascularization and damage recovery processes of ischemic tissues. This work demonstrates the applicability of fluorescence nanothermometry for ischemia detection and treatment, as well as a tool for early diagnosis of cardiovascular disease.


Assuntos
Raios Infravermelhos , Isquemia/diagnóstico por imagem , Medições Luminescentes/métodos , Pontos Quânticos/química , Termômetros , Termometria/métodos , Animais , Camundongos
17.
Asian Pac J Cancer Prev ; 16(7): 3035-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25854402

RESUMO

BACKGROUND: Isorhamnetin (Iso), a novel and essential monomer derived from total flavones of Hippophae rhamnoides that has long been used as a traditional Chinese medicine for angina pectoris and acute myocardial infarction, has also shown a spectrum of antitumor activity. However, little is known about the mechanisms of action Iso on cancer cells. OBJECTIVES: To investigate the effects of Iso on A549 lung cancer cells and underlying mechanisms. MATERIALS AND METHODS: A549 cells were treated with 10~320 µg/ml Iso. Their morphological and cellular characteristics were assessed by light and electronic microscopy. Growth inhibition was analyzed by MTT, clonogenic and growth curve assays. Apoptotic characteristics of cells were determined by flow cytometry (FCM), DNA fragmentation, single cell gel electrophoresis (comet) assay, immunocytochemistry and terminal deoxynucleotidyl transferase nick end labeling (TUNEL) . Tumor models were setup by transplanting Lewis lung carcinoma cells into C57BL/6 mice, and the weights and sizes of tumors were measured. RESULTS: Iso markedly inhibited the growth of A549 cells with induction of apoptotic changes. Iso at 20 µg/ml, could induce A549 cell apoptosis, up-regulate the expression of apoptosis genes Bax, Caspase-3 and P53, and down-regulate the expression of Bcl-2, cyclinD1 and PCNA protein. The tumors in tumor-bearing mice treated with Iso were significantly smaller than in the control group. The results of apoptosis-related genes, PCNA, cyclinD1 and other protein expression levels of transplanted Lewis cells were the same as those of A549 cells in vitro. CONCLUSIONS: Iso, a natural single compound isolated from total flavones, has antiproliferative activity against lung cancer in vitro and in vivo. Its mechanisms of action may involve apoptosis of cells induced by down-regulation of oncogenes and up-regulation of apoptotic genes.


Assuntos
Proliferação de Células/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Quercetina/análogos & derivados , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Lewis/dietoterapia , Carcinoma Pulmonar de Lewis/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Antígeno Nuclear de Célula em Proliferação/metabolismo , Quercetina/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo
18.
Adv Mater ; 27(32): 4781-7, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26174612

RESUMO

Hybrid nanostructures containing neodymium-doped nanoparticles and infrared-emitting quantum dots constitute highly sensitive luminescent thermometers operating in the second biological window. They demonstrate that accurate subtissue fluorescence thermal sensing is possible.


Assuntos
Nanocompostos/química , Nanotecnologia/métodos , Termômetros , Ácido Láctico/química , Medições Luminescentes , Nanopartículas/química , Neodímio/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Pontos Quânticos/química , Temperatura
19.
J Thorac Dis ; 6(2): E19-21, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24605240

RESUMO

In this case, a patient presented with a large primary midtracheal tumor posterior to the innominate vein and brachiocephalic artery. The left innominate vein (LIV) was temporarily transected to attain proper access to the tumor. After complete removal of the tumor, the vessel was reanastomosed. The operation was uneventful, and the patient recovered well. Temporary transection of the LIV appears to be a reasonable alternative to surgical resection in such a large cross-border midtracheal tumor.

20.
Drug Des Devel Ther ; 8: 1527-38, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25284985

RESUMO

Tumor-associated macrophages play an important role in tumor growth and progression. These macrophages are heterogeneous with diverse functions, eg, M1 macrophages inhibit tumor growth, whereas M2 macrophages promote tumor growth. In this study, we found that IFNγ and/or celecoxib (cyclooxygenase-2 inhibitor) treatment consistently inhibited tumor growth in a mouse lung cancer model. IFNγ alone and celecoxib alone increased the percentage of M1 macrophages but decreased the percentage of M2 macrophages in the tumors, and thus the M2/M1 macrophage ratio was reduced to 1.1 and 1.7 by IFNγ alone and celecoxib alone, respectively, compared to the M2/M1 macrophage ratio of 4.4 in the control group. A combination of IFNγ and celecoxib treatment reduced the M2/M1 macrophage ratio to 0.8. Furthermore, IFNγ and/or celecoxib treatment decreased expression of matrix metalloproteinase (MMP)-2, MMP-9, and VEGF, as well as the density of microvessels in the tumors, compared to the control group. This study provides the proof of principle that IFNγ and/or celecoxib treatment may inhibit lung-tumor growth through modulating the M2/M1 macrophage ratio in the tumor microenvironment, suggesting that IFNγ and celecoxib have potential to be further optimized into a new anticancer therapy.


Assuntos
Antineoplásicos/farmacologia , Interferon gama/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Pirazóis/farmacologia , Sulfonamidas/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Animais , Antineoplásicos/química , Celecoxib , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Interferon gama/química , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos C57BL , Pirazóis/química , Relação Estrutura-Atividade , Sulfonamidas/química
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