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1.
Appl Opt ; 63(1): 255-262, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38175028

RESUMO

The development of optical tweezers aims to extend their operating function and pattern. However, excessive programming can lead to a decrease in the system's operating speed and introduce bugs or data transmission delays. In this study, we present a time-shared optical tweezers system that allows for parallel operation of multiple functions. To enable efficient data transmission, we employ a queue structure and a buffer. To assess the system's performance, we utilize a biological sample in conjunction with the optical tweezers system and scanning imaging technique. We quantify the trapping parameter while concurrently running power stabilization programs. As a result, the standard deviation of the measured stiffness is reduced by 60% in the x and y directions and 30% in the z direction, indicating a significant improvement in calibration precision. Throughout the program execution, the system maintains an operating rate of 110 kHz, and the data are continuously updated in real time on the host. The system's performance demonstrates its potential for quantification and morphological reconstruction of biological samples.

2.
Org Biomol Chem ; 21(44): 8918-8923, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37906112

RESUMO

An efficient electrochemical selenocyclization strategy for the synthesis of 3-selenylindoles from 2-ethynylanilines and diselenides has been developed in simple tube- or beaker-type undivided cells under ambient conditions. Notably, these sustainable transformations are completed within a short time with low equivalents of charges, diselenides and electrolytes, exhibiting a broad substrate scope with excellent functional group compatibility. Moreover, a gram-scale electrosynthesis and late-stage functionalization of complex molecules further demonstrate the practical synthetic potential of this facile electrochemical system.

3.
Anal Chem ; 91(6): 3912-3920, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30761890

RESUMO

The precise monitoring of H2S has aroused immense research interest in the biological and biomedical fields since it is exposed as a third endogenous gasotransmitter. Hence, there is an urgent requisite to explore an ultrasensitive and economical H2S detection system. Herein, we report a simple strategy to configure an extremely sensitive electrochemical sensor with a 2D nanosheet-shaped layered double hydroxide (LDH) wrapped carbon nanotubes (CNTs) nanohybrid (CNTs@LDH), where a series of CNTs@CuMn-LDH nanohybrids with varied amounts of LDH nanosheets grafted on a conductive CNTs backbone has been synthesized via a facile coprecipitation approach. Taking advantage of the unique core-shell structure, the integrated electrochemically active CuMn-LDH nanosheets on the conductive CNTs scaffold, the maximum interfacial collaboration, and the superior specific surface area with a plethora of surface active sites and ultrathin LDH layers, the as-prepared CNTs@CuMn-LDH nanoarchitectures have exhibited superb electrocatalytic activity toward H2S oxidation. Under the optimum conditions, the electrochemical sensor based on the CNTs@CuMn-LDH nanohybrid shows remarkable sensing performances for H2S determination in terms of a wide linear range and a low detection limit of 0.3 nM (S/N = 3), high selectivity, reproducibility, and durability. With marvelous efficiency achieved, the proposed sensing platform has been practically used in in situ detection of abiotic H2S efflux produced by sulfate reducing bacteria and real-time in vitro tracking of H2S concentrations from live cells after being excreted by a stimulator which in turn might serve as early diseases diagnosis. Thus, our core-shell hybrid nanoarchitectures fabricated via structural integration strategy will open new horizons in material synthesis, biosensing systems, and clinical chemistry.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Peróxido de Hidrogênio/análise , Peróxido de Hidrogênio/metabolismo , Hidróxidos/química , Nanotubos de Carbono/química , Proteoma/análise , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Caseínas/química , Eletrodos , Transição Epitelial-Mesenquimal , Escherichia coli/metabolismo , Células HeLa , Humanos , Limite de Detecção , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Processamento de Proteína Pós-Traducional , Fator de Crescimento Transformador beta/farmacologia
4.
J Org Chem ; 84(11): 6895-6903, 2019 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-31066270

RESUMO

A direct defluorinative multifluoroarylation of unactivated sp3 C-H bonds through hydrogen atom transfer using photoredox catalysis has been developed. The C(sp3)-C(sp2) couplings between C(sp2)-F bonds and corresponding C(sp3)-H bonds adjacent to heteroatoms proceeded smoothly to afford the desired products in moderate to good yields. Preliminary mechanistic investigations on this novel transformation revealed that the C-H cleavage process might be involved in the rate-determining step.

5.
Mikrochim Acta ; 186(10): 671, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31489483

RESUMO

This review (with 105 references) describes the progress that has been made in the past few years in the use of 2D nanoarchitectures in electrochemical sensors for the clinically highly significant parameters hydrogen peroxide, glucose and dopamine. Following an introduction into the field, we summarize the improvements in electrochemical sensors that can be accomplished by using such nanomaterials, with a specific focus on sensors for in-vitro diagnostics. A further large section covers sensors based on the use of layered double hydroxides (LDHs), with subsections on sensors for hydrogen peroxide, glucose and dopamine. Dichalcogenides based electrochemical sensors are treated in next section, again with subsections on hydrogen peroxide, glucose and dopamine. We also summarize key sensor parameters including limits of detection, linear ranges and real time applications in pharmaceutical, environmental and clinical fields. The next section summarizes the work related to sensing of hydrogen peroxide released from different live cells as signalling molecule indicating cellular stress. The review concludes with a discussion of current challenges and future perspectives. Graphical abstract Schematic illustration of layered double hydroxides (LDHs) and dichalcogenides based electrochemical sensors for sensitive determination of hydrogen peroxide (H2O2), glucose and dopamine (DA) from biological fluids as biomarkers for early diagnosis.

6.
Mol Cancer ; 17(1): 131, 2018 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-30153823

RESUMO

Liquid biopsy by genotyping circulating tumor DNA (ctDNA) has provided a non-invasive approach in assessing tumor genomic alterations in clinical oncology. However, emerging evidence in clinical settings has shown significant discordance in the genomic alterations between matched tumor tissue and blood ctDNA samples, and even between the same set of blood samples analyzed on different testing platforms. Thus, it is necessary to study underlying causes of discrepancies in these studies by genotyping tumor tissue and ctDNA in parallel using next generation sequencing (NGS) panels based on the same technology. Here we enrolled 56 non-small-cell lung cancer (NSCLC) patients and evaluated tumor tissue genotyping and ctDNA based liquid biopsy by parallel NGS panel testing and compared different sample preparation conditions. Somatic mutations in plasma cell-free DNA (cfDNA) were detected in 63.6% patients with early-stage NSCLC and 60% patients with advanced-stage NSCLC. The overall concordance between matched formalin-fixed paraffin-embedded sample and cfDNA was 54.6% in early-stage NSCLC patients and 80% in advanced-stage NSCLC patients. The positive concordance rate was 44.4% and 71.4% in early-stage and advanced-stage patients, respectively. Using fresh frozen tumor samples did not improve the overall concordance rate between matched tumor tissue and cfDNA. Processing blood samples beyond 4 h after blood draw significantly decreased the detection rate of somatic mutations in cfDNA. Thus, the concordance rate between tumor tissue-based and ctDNA-based genotyping in clinical samples can be affected by multiple pre-analytical, analytical and biologic factors. Parallel NGS panel testing on both sample types for each patient may be warranted for effective guidance of cancer targeted therapies and possible early detection of cancer.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , DNA Tumoral Circulante/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Neoplasias Pulmonares/genética , Mutação , Análise de Sequência de DNA/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Biópsia Líquida , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias
7.
J Org Chem ; 83(17): 9696-9706, 2018 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-30067027

RESUMO

Here we describe a straightforward and efficient approach for regiospecific introduction of an allyl group into cycloalkanol molecules employing a visible-light-mediated ring-opening strategy. A wide range of distally allylated or formylated ketones is furnished from 1-aryl cycloalkanol precursors of variable ring sizes, providing a concise and practical access for the modification of complex natural products. Preliminary mechanistic studies demonstrate that the key O-centered radicals mediate the sequential ring cleavage and allylation/formylation.

8.
J Biol Chem ; 291(19): 10363-71, 2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-26994136

RESUMO

Integrin-mediated rolling and firm cell adhesion are two critical steps in leukocyte trafficking. Integrin α4ß1 mediates a mixture of rolling and firm cell adhesion on vascular cell adhesion molecule-1 (VCAM-1) when in its resting state but only supports firm cell adhesion upon activation. The transition from rolling to firm cell adhesion is controlled by integrin activation. Kindlin-3 has been shown to bind to integrin ß tails and trigger integrin activation via inside-out signaling. However, the role of kindlin-3 in regulating resting α4ß1-mediated cell adhesion is not well characterized. Herein we demonstrate that kindlin-3 was required for the resting α4ß1-mediated firm cell adhesion but not rolling adhesion. Knockdown of kindlin-3 significantly decreased the binding of kindlin-3 to ß1 and down-regulated the binding affinity of the resting α4ß1 to soluble VCAM-1. Notably, it converted the resting α4ß1-mediated firm cell adhesion to rolling adhesion on VCAM-1 substrates, increased cell rolling velocity, and impaired the stability of cell adhesion. By contrast, firm cell adhesion mediated by Mn(2+)-activated α4ß1 was barely affected by knockdown of kindlin-3. Structurally, lack of kindlin-3 led to a more bent conformation of the resting α4ß1. Thus, kindlin-3 plays an important role in maintaining a proper conformation of the resting α4ß1 to mediate both rolling and firm cell adhesion. Defective kindlin-3 binding to the resting α4ß1 leads to a transition from firm to rolling cell adhesion on VCAM-1, implying its potential role in regulating the transition between integrin-mediated rolling and firm cell adhesion.


Assuntos
Integrina alfa4beta1/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Transdução de Sinais/fisiologia , Adesão Celular/fisiologia , Humanos , Integrina alfa4beta1/genética , Células K562 , Manganês/metabolismo , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Ligação Proteica , Resistência ao Cisalhamento , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
9.
J Org Chem ; 82(3): 1389-1402, 2017 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-28054780

RESUMO

A novel and efficient method for the synthesis of highly substituted benzobicyclo[2.2.2]octane skeletons has been explored. Under UV-light irradiation, o-divinylbenzenes underwent a pericyclic reaction to form the cyclic o-quinodimethane intermediates which were subsequently reacted with olefins through [4+2] addition to construct the benzobicyclo[2.2.2]octane skeletons in mild conditions. Gram scale reactions demonstrated the synthetic potential application of this protocol.

10.
J Org Chem ; 82(15): 7856-7868, 2017 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-28699349

RESUMO

The photolysis of substituted o-divinylbenzenes promotes a one-step and metal-free conversion to oxatricycles at room temperature. Irradiation o-divinylbenzenes results in an pericyclic reaction to form cyclic o-quinodiemthane intermediates, which subsequently undergo intramolecular oxa-[4+2] cycloaddition to form oxacyclic derivatives.

11.
Ren Fail ; 37(4): 694-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25715637

RESUMO

Acute kidney injury (AKI) is one of the most common complications in patients with severe sepsis. The development of septic AKI increases patients' mobility and even mortality. Toll-like receptor 2 (TLR2), as a membrane surface receptor for bacterial, fungal, viral and certain endogenous substances, has been described to contribute to the development of septic AKI; however, the renal cell types associating TLR2 overactivation in septic AKI has not been described. In the current study, we investigated the TLR2 activation patterns in the kidney of lipopolysaccharide-induced septic AKI mice. Our results demonstrated that mRNA level of TLR2 significantly increased in the kidney of lipopolysaccharide-treated mice. Immunohistochemistry revealed the overactivation of TLR2 in the glomeruli. Double immunofluorescence analysis shows the precise distribution of TLR2 by showing the colocalization of TLR2 in glomeruli with synaptopodin, a podocyte marker, and Tie2, an endothelial marker. In addition, proapoptotic molecules Bax and Caspase-3 were increased in the glomeruli of lipopolysaccharide-treated mice. Together, the current study indicates that TLR2 is overactivated in the glomerular endothelial cells and podocytes in septic AKI mice, while the abundance of Bax and Caspase-3 were increased in the glomeruli of these mice, it may supply a clue that TLR2 induced these cell apoptosis in AKI. This finding provides an alternative mechanism to understand AKI development and potential targets for treatment.


Assuntos
Injúria Renal Aguda/metabolismo , Células Endoteliais/metabolismo , Podócitos/metabolismo , Receptor 2 Toll-Like/biossíntese , Animais , Modelos Animais de Doenças , Glomérulos Renais/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C
12.
ACS Appl Mater Interfaces ; 16(14): 18063-18074, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38537174

RESUMO

Bacterial infections have become a serious threat to public health. The utilization of antibacterial textiles offers an effective way to combat bacterial infections at the source, instead of relying solely on antibiotic consumption. Herein, efficient and durable antibacterial fibers based on quercetin and cellulose were prepared by a triaxial microfluidic spinning technology using ionic liquids (ILs) as the solvents. It was indicated that the structure and properties of the antibacterial fibers were affected by the type of IL and the flow rates during the triaxial microfluidic spinning process. Quercetin regenerated from [Emim]Ac underwent structural transformation and obtained an increased water solubility, while quercetin regenerated from [Emim]DEP remained unchanged, which was proven by FI-IR, XRD, and UV analyses. Furthermore, antibacterial fibers regenerated from [Emim]Ac exhibited the highest antibacterial activity of 96.9% against S. aureus, achieved by reducing the inner-to-outer flow rate ratio to 0 and concentrating quercetin at the center of fibers. On the other hand, when [Emim]DEP was used as the solvent, balancing the inner-to-outer flow rate ratio to concentrate quercetin in the middle layer of the fiber was optimal for achieving the best antibacterial activity of 93.3% because it promised both the higher encapsulation efficiency and release rate. Computational fluid dynamics (CFD) mathematically predicted the solvent exchange process during triaxial spinning, explaining the influence of IL types and flow rates on quercetin distribution and encapsulation efficiency. It was indicated that optimizing the distribution of antibacterial agents within the fibers can fully unleash its antibacterial potential while preserving the mechanical properties of the fiber. Therefore, the proposed simple triaxial spinning strategy provides valuable insights into the design of biomedical materials.


Assuntos
Infecções Bacterianas , Líquidos Iônicos , Humanos , Solventes/química , Líquidos Iônicos/farmacologia , Líquidos Iônicos/química , Microfluídica , Staphylococcus aureus , Quercetina/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química
13.
Materials (Basel) ; 17(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38612154

RESUMO

Controlling infrared thermal radiations can significantly improve the environmental adaptability of targets and has attracted increasing attention in the field of thermal camouflage. Thermal emitters based on Ge2Sb2Te5 (GST) can flexibly change their radiation energy by controlling the reversible phase transition of GST, which possesses fast switching speed and low power consumption. However, the feasibility of the dynamic regulation of GST emitters lacks experimental and simulation verification. In this paper, we propose an electrically tunable thermal emitter consisting of a metal-insulator-metal plasmonic metasurface based on GST. Both optical and thermal simulations are conducted to optimize the structural parameters of the GST emitter. The results indicate that this emitter possesses large emissivity tunability, wide incident angle, polarization insensitivity, phase-transition feasibility, and dynamic thermal camouflage capability. Therefore, this work proposes a reliable optimization method to design viable GST-based thermal emitters. Moreover, it provides theoretical support for the practical application of phase-change materials in dynamic infrared thermal camouflage technology.

14.
Micromachines (Basel) ; 14(2)2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36837974

RESUMO

Safety and reliability are essential engineering concerns for energy-harvesting installations. In the case of the piezoelectric galloping energy harvester, there is a risk that excessive wake galloping may lead to instability, overload, and thus damage. With this in mind, this paper studies bivariate statistics of the extreme, experimental galloping energy harvester dynamic response under realistic environmental conditions. The bivariate statistics were extracted from experimental wind tunnel results, specifically for the voltage-force data set. Authors advocate a novel general-purpose reliability approach that may be applied to a wide range of dynamic systems, including micro-machines. Both experimental and numerically simulated dynamic responses can be used as input for the suggested structural reliability analysis. The statistical analysis proposed in this study may be used at the design stage, supplying proper characteristic values and safeguarding the dynamic system from overload, thus extending the machine's lifetime. This work introduces a novel bivariate technique for reliability analysis instead of the more general univariate design approaches.

15.
Bioelectrochemistry ; 150: 108367, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36621048

RESUMO

Stainless steels (SS) are not immune to microbiologically influenced corrosion (MIC) especially in the presence of sulfate reducing bacteria (SRB). It is necessary to study the influence of alloying elements on the MIC. SRB MIC behaviors of four stainless steels (2205 SS, 316L SS, 304 SS, and 410 SS), with different alloying element compositions were compared after 14 days of incubation at 37°C in enriched artificial seawater inoculated with Desulfovibrio sp. The sessile cell sequence was 410 SS > 316L SS > 304 SS > 2205 SS, inversely proportional to Cr content. The uniform corrosion rate (based on weight loss) sequence was 410 SS > 304 SS > 316L SS > 2205 SS, which matches the pitting resistance equivalent number (PREN) sequence inversely. 410 SS with the lowest Cr and Mo contents suffered the most severe pitting, with pit depth of 35 µm and weight loss of 0.75 mg/cm2 (0.91 mm/a pitting rate and 25 µm/a uniform corrosion rate). The other three stainless steels with higher Cr and Mo contents suffered only metastable pits. The semiconductor characteristics and the re-passivation abilities of the passive films were found to be affected by Cr and Mo contents.


Assuntos
Desulfovibrio , Aço , Aço Inoxidável , Ligas , Corrosão , Anaerobiose , Água do Mar
16.
Dalton Trans ; 52(2): 476-486, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36530126

RESUMO

Oxygen-containing organics, which are generated from the selective oxidation of their corresponding hydrocarbons, have high value in the chemical and pharmaceutical industries. However, their oxidation reactions are very challenging as the products are more active than the substrates, especially for the oxidation of cyclohexane (CHA). Herein, we focused on the one-step preparation of Bi2WO6 with double active sites of tunable metallic Bi and oxygen vacancies (OV-Bi/Bi2WO6) by a facile solvothermal treatment. Then, OV-Bi/Bi2WO6 was used as an efficient photocatalyst for the partial oxidation of CHA to cyclohexanone (CHA-one) for the first time in air as an oxidant under solvent-free and room temperature conditions. The Bi : Bi2WO6 ratio in the as-prepared OV-Bi/Bi2WO6 heterojunction could be tailored from 0.08 to 8.43 by controlling the solvothermal temperature, and the synergistic effect between DMF and EG could increase the reduction of MDF/EG and promote the production of Bi. Moreover, OV-Bi/Bi2WO6-160 yielded 4.4 and 8.8 times more CHA-one (128.8 µmol) than pure Bi2WO6 and metallic Bi, respectively, and achieved 93.6% selectivity to CHA-one in air as an oxidant under solvent-free conditions. The results revealed that the highly enhanced photocatalytic activity was mainly attributed to the superior specific surface area, outstanding photo-absorption, abundant oxygen vacancies, and efficient electron-hole separation. Moreover, for the unique double active sites in OV-Bi/Bi2WO6, oxygen vacancies can enhance the adsorption and activation capacity of Bi2WO6 for O2, while metallic Bi can improve the adsorption and activation capacity of Bi2WO6 for CHA. Meanwhile, OV-Bi/Bi2WO6 also exhibited excellent durability due to the strong interaction between metallic Bi and Bi2WO6. The present work provides a flexible approach for tailoring the Bi : Bi2WO6 ratio and outlines an effective method for producing CHA-one from CHA under mild conditions.

17.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 6): o1852, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22719617

RESUMO

The asymmetric unit of the title compound, C(18)H(11)BrN(2)O(2), contains two independent mol-ecules in which the prop-2-ynyl-amino groups have different mutual orientations. In one mol-ecule, the Br atom is disordered over two positions, with refined occupancies of 0.742 (2) and 0.258 (2).

18.
Zhen Ci Yan Jiu ; 47(7): 636-9, 2022 Jul 25.
Artigo em Zh | MEDLINE | ID: mdl-35880282

RESUMO

OBJECTIVE: To compare the clinical effects on osteonecrosis of the femoral head between the comprehensive therapy (electroacupuncture ï¼»EAï¼½ of quintuple needling combined with adductor relaxation method) and the adductor relaxation method. METHODS: Eighty patients with osteonecrosis of the femoral head were randomly allocated into a treatment group and a control group, with 40 patients in each group. The patients in the control group were treated with the adductor relaxation method. In the treatment group, besides the treatment as the control group, EA of quintuple needling was exerted at the most obvious tender sites (Ashi points) around the hip joint, 30 min each time. The treatment was given once daily, 30 days as one session of treatment, and 3 sessions were required totally in each group. The clinical effects of two groups were evaluated. The score of visual analogue scale (VAS), Harris score and the score of the hip mobility were compared before and after treatment and between the two groups. RESULTS: The total effective rate was 97.5% (39/40) in the treatment group, higher than 82.5% (33/40) in the control group (P<0.05). Compared with before treatment, the VAS score was remarkably decreased (P<0.05), while the Harris score and the score of the hip mobility were apparently increased in either group after treatment (P<0.05). In comparison between two groups, the VAS score in the treatment group was obviously lower (P<0.05) than that of the control group, while the Harris score and the score of the hip mobility were higher than those of the control group (P<0.05). CONCLUSION: EA of quintuple needling combined with the adductor relaxation method obtains the better clinical effects on ischemic osteonecrosis of the femoral head compared with the simple adductor relaxation method, and this comprehensive therapy obviously relieves the clinical symptoms in patients.


Assuntos
Eletroacupuntura , Osteonecrose , Pontos de Acupuntura , Eletroacupuntura/métodos , Cabeça do Fêmur , Humanos , Medição da Dor , Resultado do Tratamento
19.
Front Oncol ; 12: 1024655, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387208

RESUMO

Transformation of small cell lung cancer (SCLC) to lung adenocarcinoma (LUAD) is rarely reported. Here, we report a case initially presented with SCLC and was diagnosed as LUAD when the lesion relapsed at the same site. A 56-year-old patient with SCLC who received etoposide and cisplatin chemotherapy combined with radiotherapy achieved a complete radiological response. After 28 months of stable disease, a computed tomography scan revealed a new lesion at the same site as the primary tumor. Pathological examination suggested a LUAD with an emerging EGFR exon 19 deletion. The patient was then treated with icotinib and achieved a near-complete radiological response. Nineteen months later, the patient developed resistance caused by EGFR T790M mutation and received treatment with osimertinib. At the last follow-up in January 2022, the patient was symptom-free. This case warrants re-biopsy and genetic testing as a routine operation when SCLC relapses at the same site as the primary tumor for an extended period, and prospective investigation is required.

20.
Oncogene ; 41(34): 4091-4103, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35854065

RESUMO

Tumor metastasis is the leading cause of cancer-associated mortality. Unfortunately, the underlying mechanism of metastasis is poorly understood. Expression of legumain (LGMN), an endo-lysosomal cysteine protease, positively correlates with breast cancer metastatic progression and poor prognosis. Here, we report that LGMN is secreted in the zymogen form by motile breast cancer cells. Through binding to cell surface integrin αvß3 via an RGD motif, the autocrine pro-LGMN activates FAK-Src-RhoA signaling in cancer cells and promotes cancer cell migration and invasion independent of LGMN protease activity. Either silencing LGMN expression or mutationally abolishing pro-LGMN‒αvß3 interaction significantly inhibits cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Finally, we developed a monoclonal antibody against LGMN RGD motif, which blocks pro-LGMN‒αvß3 binding, and effectively suppresses cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Thus, disruption of pro-LGMN‒integrin αvß3 interaction may be a potentially promising strategy for treating breast cancer metastasis.


Assuntos
Neoplasias da Mama , Integrina alfaVbeta3 , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Cisteína Endopeptidases , Feminino , Humanos , Integrina alfaVbeta3/genética , Integrina alfaVbeta3/metabolismo , Metástase Neoplásica , Oligopeptídeos
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