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1.
Cell Biol Toxicol ; 40(1): 12, 2024 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340268

RESUMO

V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA), a novel negative checkpoint regulator, plays an essential role in allergic pulmonary inflammation in mice. Treatment with a VISTA agonistic antibody could significantly improve asthma symptoms. Thus, for allergic asthma treatment, VISTA targeting may be a compelling approach. In this study, we examined the functional mechanism of VISTA in allergic pulmonary inflammation and screened the FDA-approved drugs for VISTA agonists. By using mass cytometry (CyTOF), we found that VISTA deficiency primarily increased lung macrophage infiltration in the OVA-induced asthma model, accompanied by an increased proportion of M1 macrophages (CD11b+F4/80+CD86+) and a decreased proportion of M2 macrophages (CD11b+F4/80+CD206+). Further in vitro studies showed that VISTA deficiency promoted M1 polarization and inhibited M2 polarization of bone marrow-derived macrophages (BMDMs). Importantly, we discovered baloxavir marboxil (BXM) as a VISTA agonist by virtual screening of FDA-approved drugs. The surface plasmon resonance (SPR) assays revealed that BXM (KD = 1.07 µM) as well as its active form, baloxavir acid (BXA) (KD = 0.21 µM), could directly bind to VISTA with high affinity. Notably, treatment with BXM significantly ameliorated asthma symptoms, including less lung inflammation, mucus secretion, and the generation of Th2 cytokines (IL-5, IL-13, and IL-4), which were dramatically attenuated by anti-VISTA monoclonal antibody treatment. BXM administration also reduced the pulmonary infiltration of M1 macrophages and raised M2 macrophages. Collectively, our study indicates that VISTA regulates pulmonary inflammation in allergic asthma by regulating macrophage polarization and baloxavir marboxil, and an old drug might be a new treatment for allergic asthma through targeting VISTA.


Assuntos
Asma , Dibenzotiepinas , Pneumonia , Piridonas , Triazinas , Animais , Camundongos , Asma/tratamento farmacológico , Asma/metabolismo , Morfolinas/farmacologia , Morfolinas/uso terapêutico
2.
Bioorg Med Chem ; 108: 117787, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38838580

RESUMO

19 derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides (H1-H19) and 5 derivatives of 1-benzyl-5-arylpyrazole-3-carboxamides (J1-J5) have been designed and synthesized as potential negative allosteric modulators (NAMs) for the ß2-adrenergic receptor (ß2AR). The new pyrazole derivatives were screened on the classic G-protein dependent signaling pathway at ß2AR. The majority of 1-benzyl-3-aryl-pyrazole-5-carboxamide derivatives show more potent allosteric antagonistic activity against ß2AR than Cmpd-15, the first reported ß2AR NAM. However, the 1-benzyl-5-arylpyrazole-3-carboxamide derivatives exhibit very poor or even no allosteric antagonistic activity for ß2AR. Furthermore, the active pyrazole derivatives have relative better drug-like profiles than Cmpd-15. Taken together, we discovered a series of derivatives of 1-benzyl-3-arylpyrazole-5-carboxamides as a novel scaffold of ß2AR NAM.


Assuntos
Receptores Adrenérgicos beta 2 , Receptores Adrenérgicos beta 2/metabolismo , Receptores Adrenérgicos beta 2/química , Regulação Alostérica/efeitos dos fármacos , Humanos , Relação Estrutura-Atividade , Pirazóis/química , Pirazóis/farmacologia , Pirazóis/síntese química , Estrutura Molecular , Antagonistas de Receptores Adrenérgicos beta 2/farmacologia , Antagonistas de Receptores Adrenérgicos beta 2/química , Antagonistas de Receptores Adrenérgicos beta 2/síntese química
3.
Chem Biodivers ; : e202401420, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287370

RESUMO

We designed and synthesized 27 new amide and dipeptide derivatives containing a substituted phenylalanine as negative allosteric modulators (NAMs) for the beta-2 adrenergic receptor (ß2AR). These analogs aimed to improve the activity of our lead compound, Cmpd-15, by introducing variations in three key regions: the meta-bromobenzyl methylbenzamide (S1), para-formamidophenylalanine (S2), and 1-cyclohexyl-1-phenylacetyl (S3) groups. The synthesis involved the Pd-catalyzed ß-C(sp3)-H arylation of N-acetylglycine with 1-iodo-4-substituent-benzenes as the key step. GloSensor cAMP accumulation assay revealed that six analogs (A1, C5, C6, C13, C15 and C17) surpass Cmpd-15 in ß2AR allosteric function. This highlights the crucial role of the S1 region (meta-bromobenzyl methylbenzamide) in ß2AR allostery while suggesting potential replaceability of the S2 region (para-formamidophenylalanine). These findings serve as a valuable springboard for further optimizing Cmpd-15, potentially leading to smaller, more active, and more stable ß2AR-targeting NAMs.

4.
Molecules ; 29(19)2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39407678

RESUMO

A fluorescent probe based on ternary AgFeS2 quantum dots has been prepared for the design of ternary chalcogenides. The nanoparticles are synthesized with oleylamine as a stabilizer at a low temperature (particle size in the range of 2 to 3 nm) and they exhibit an intense blue emission in aqueous media. As for their internal structure, each nanoparticle's relative stoichiometric ratio (AgFe1.01S1.91) is very close to the theoretical value of 1:1:2. Their magnetic properties have been studied with a vibrating sample magnetometer and they have ferromagnetism between 4 K and 298 K (applied magnetic field ranging between -10,000 and 10,000 Oe). In the presence of iodide ions, the emission at 458 nm derived from AgFeS2 QDs has been observed to give rise to fluorescence quenching. The detection system is based on a static quenching process and morphological change between iodide ions and AgFeS2, which has a good linear range from 0 to 37.5 µmol/L, with a limit of detection of 0.99 µM. The nanoprobe responds within 30 s for the efficient detection of iodide. Such functional quantum dots will provide a powerful indicator in environmental and bio-sensing applications.

5.
Cell Commun Signal ; 21(1): 327, 2023 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974196

RESUMO

Regulated cell death (RCD) is a regulable cell death that involves well-organized signaling cascades and molecular mechanisms. RCD is implicated in fundamental processes such as organ production and tissue remodeling, removing superfluous structures or cells, and regulating cell numbers. Previous studies have not been able to reveal the complete mechanisms, and novel methods of RCD are constantly being proposed. Two metal ions, iron (Fe) and copper (Cu) are essential factors leading to RCDs that not only induce ferroptosis and cuproptosis, respectively but also lead to cell impairment and eventually diverse cell death. This review summarizes the direct and indirect mechanisms by which Fe and Cu impede cell growth and the various forms of RCD mediated by these two metals. Moreover, we aimed to delineate the interrelationships between these RCDs with the distinct pathways of ferroptosis and cuproptosis, shedding light on the complex and intricate mechanisms that govern cellular survival and death. Finally, the prospects outlined in this review suggest a novel approach for investigating cell death, which may involve integrating current therapeutic strategies and offer a promising solution to overcome drug resistance in certain diseases. Video Abstract.


Assuntos
Ferroptose , Morte Celular Regulada , Morte Celular , Cobre , Ferro , Apoptose
6.
Cell Biol Toxicol ; 39(6): 3287-3304, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37804401

RESUMO

V-domain immunoglobulin suppressor of T-cell activation (VISTA), an important negative checkpoint protein, participates in immunoregulation. Systemic lupus erythematosus (SLE) is an autoimmune disease in which patients exhibit high levels of autoantibodies and multi-organ tissue injury, primarily involving the kidney and skin. In wild-type (WT) mice and Vsir-/- mice with pristane-induced lupus-like disease, we found that VISTA deficiency exacerbated the lupus-like disease in mice, possibly through aberrant activation of type I interferon (IFN-I) signaling, CD4+ T cell, and noncanonical nuclear factor-κB (NF-κB) pathway. Surface plasmon resonance results showed that imatinib, an FDA-approved tyrosine kinase inhibitor, may have a high affinity for human VISTA-ECD with a KD value of 0.2009 µM. The biological activities of imatinib and VISTA agonist M351-0056 were studied in monocytes and T cells and in lupus-like disease murine model of chronic graft-versus-host disease (cGVHD) and lupus-prone MRL/lpr mice. VISTA small-molecule agonist reduced the cytokine production of peripheral blood mononuclear cells (PBMCs) and Jurkat cells and inhibited PBMCs proliferation. Moreover, they attenuated the levels of autoantibodies, renal injury, inflammatory cytokines, chemokines, and immune cell expansion in the cGVHD mouse model and MRL/lpr mice. Our findings also demonstrated that VISTA small-molecule agonist ameliorated the development of SLE through improving aberrantly activated IFN-I signaling and noncanonical NF-κB pathway. In conclusion, VISTA has a protective effect on the development and progression of SLE. VISTA agonist M351-0056 and imatinib have been firstly demonstrated to attenuate SLE, suggesting interventions to enhance VISTA function may be effective in treating SLE. VISTA deficiency exacerbates pristane-induced lupus-like disease in mice by promoting activation of the IFN-I and noncanonical NF-κB pathway. Imatinib was screened as a small-molecule VISTA agonist by molecular docking, SPR, and cellular level experiments. VISTA agonists (M351-0056 and imatinib) alleviated lupus-like disease progression in the cGVHD mouse model and MRL/lpr mice by inhibiting activation of IFN-I and noncanonical NF-κB pathway.


Assuntos
Lúpus Eritematoso Sistêmico , NF-kappa B , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Mesilato de Imatinib/farmacologia , Interferons , Leucócitos Mononucleares , Simulação de Acoplamento Molecular , Camundongos Endogâmicos MRL lpr , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/metabolismo , Citocinas/metabolismo , Autoanticorpos , Modelos Animais de Doenças
7.
Bioorg Med Chem ; 92: 117418, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37536263

RESUMO

In this study, twenty-two novel cholic acid (CA) derivatives were designed and synthesized as potential Takeda G protein-coupled receptor 5 (TGR5) positive allosteric modulators (PAMs) using structure-based drug design (SBDD). GloSensor cAMP accumulation assay was employed to assess the functional activity and allosteric mechanism of final compounds. Biological results showed that all target compounds were able to activate the TGR5 in the cAMP formation assay. Remarkably, compound B1, selective methylation of 7-OH in CA, exhibited 5-fold higher activity for TGR5 compared to that of CA. Moreover, B1 positively modulate the functional activity of chenodeoxycholic acid (CDCA) in TGR5, indicating that B1 is a TGR5 PAM. On the other hand, 12-carbonyl derivative A1 displayed 7-fold higher potency for TGR5 relative to CA. Unexpectedly, compound A1 exhibited the same positive allosteric effect as B1, suggesting that A1 is a TGR5 PAM as well. Molecular modeling study revealed that 12-carbonyl in A1 and 12-OH in B1 formed H-bolds with the key amino acid Thr131, which are significant for TGR5 allosteric property. Taken together, we found two potent TGR5 PAMs A1 and B1 through SBDD, which could be used as lead compounds to further study TGR5 allosteric functionality.


Assuntos
Desenho de Fármacos , Receptores Acoplados a Proteínas G , Ácido Cólico/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Modelos Moleculares , Regulação Alostérica
8.
Bioorg Chem ; 120: 105588, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979448

RESUMO

In this study, fourteen new cholic acid (CA) derivatives were designed and synthesized, and the GloSensor cAMP accumulation assay indicated that all derivatives could activate the Takeda G protein-coupled receptor 5 (TGR5). Methylation of 7- and 12-hydroxyl groups in CA significantly increased TGR5 agonism for the new derivatives. For example, 7,12-dimethoxy derivative B1 exhibited 78-fold higher potency for TGR5 than the 7,12-dihydroxyl derivative A1 and 258-fold higher potency than CA itself. On the other hand, A1 positively modulated chenodeoxycholic acid (CDCA) functional activity in TGR5, whereas B1 did not show similar activity. Molecular docking experiments indicated that A1 formed a hydrogen bond between the 12-OH and amino acid Thr131 of TGR5, which is significant for its allosteric property. However, methylation at the 12-hydroxyl group in CA (derivative B1) disrupted this pivotal H-bond. Therefore, the free 12-hydroxyl group is essential for the CA derivatives in TGR5 allosteric agonism. Overall, we discovered a highly potent TGR5 agonist, B1, which can be used as lead compound for further study.


Assuntos
Ácidos e Sais Biliares , Receptores Acoplados a Proteínas G , Ácido Cólico/farmacologia , Proteínas de Ligação ao GTP/metabolismo , Simulação de Acoplamento Molecular , Receptores Acoplados a Proteínas G/metabolismo
9.
BMC Cancer ; 19(1): 1188, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805975

RESUMO

BACKGROUND: An extremely rare condition, radiation-induced angiosarcoma is characterized by a poor prognosis, high recurrence rate and lack of effective treatment. Herein, we present a case report of a 48-year-old female patient with radiation-induced abdominal wall angiosarcoma who showed a dramatic response to low-dose apatinib. CASE PRESENTATION: The patient, who was diagnosed with cervical squamous cell carcinoma 20 years ago, had received radiotherapy and chemotherapy after operation. Angiosarcomas of the abdominal wall appeared 9 years later. After repeated surgical operations and intravenous chemotherapy for the angiosarcomas, the patient developed tumor recurrence and pulmonary metastasis. The abdominal wall tumors showed repeated rupture and bleeding, with poor wound healing. On evaluation, laboratory findings detected the negative serum tumor markers CEA, CA 125, CA 15-3 and CA 19-9. Imaging showed multiple subcutaneous nodules and masses in the abdominal wall, accompanied by suspected small subpleural nodule at the lower lobe of the right lung. Immunohistochemistry of previous surgical pathology indicated that CD31, ERG and Vim were positive. The result of whole exome sequencing suggested the mutations of BRAF and HRAS, and the amplification of MYC. Based on the above results, the patient was clinically diagnosed with radiation-induced angiosarcoma of the abdominal wall with pulmonary metastasis. The patient was treated with low-dose apatinib and rejected reoperation or chemotherapy. RESULTS: At the 6-month follow-up visit, the abdominal wall lesions that had previously ruptured stopped bleeding and showed significant shrinkage. Imaging showed that most of the abdominal wall lesions had partially regressed, and some of the lesions on the abdominal wall and the suspected lesion of subpleural nodule at the lower lobe of the right lung had disappeared. CONCLUSIONS: We described this case and reviewed the literature on radiation-related angiosarcoma. Importantly, this case suggests that apatinib may be an effective and sensitive treatment for radiation-induced angiosarcoma even at the lowest dosage, without aggravating the bleeding of lesions.


Assuntos
Neoplasias Abdominais/tratamento farmacológico , Hemangiossarcoma/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Induzidas por Radiação/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Piridinas/administração & dosagem , Neoplasias Abdominais/etiologia , Neoplasias Abdominais/genética , Parede Abdominal/patologia , Feminino , Amplificação de Genes , Hemangiossarcoma/etiologia , Hemangiossarcoma/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Mutação , Neoplasias Induzidas por Radiação/genética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Piridinas/uso terapêutico , Resultado do Tratamento
10.
Sensors (Basel) ; 18(5)2018 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-29734789

RESUMO

In the present work, centrifugal deposited Au-Pd core-shell nanoparticle (NP) film was proposed for the room-temperature optical detection of hydrogen gas. The size dimension of 44, 48, 54, and 62 nm Au-Pd core-shell nanocubes with 40 nm Au core were synthesized following a solution-based seed-mediated growth method. Compared to a pure Pd NP, this core-shell structure with an inert Au core could decrease the H diffusion length in the Pd shell. Through a modified centrifugal deposition process, continues film samples with different core-shell NPs were deposited on 10 mm diameter quartz substrates. Under various hydrogen concentration conditions, the optical response properties of these samples were characterized by an intensity-based optical fiber bundle sensor. Experimental results show that the continues film that was composed of 62 nm Au-Pd core-shell NPs has achieved a stable and repeatable reflectance response with low zero drift in the range of 4 to 0.1% hydrogen after a stress relaxation mechanism at first few loading/unloading cycles. Because of the short H diffusion length due to the thinner Pd shell, the film sample composed of 44 nm Au-Pd NPs has achieved a dramatically decreased response/recovery time to 4 s/30 s. The experiments present the promising prospect of this simple method to fabricate optical hydrogen sensors with controllable high sensitivity and response rate at low cost.

11.
Heliyon ; 10(1): e23799, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192825

RESUMO

Based on the panel data from 283 prefecture-level cities in China between 2009 and 2019, this study examines the impact of China's carbon emissions trading system on reducing carbon emissions and its mechanisms, using the PSM-DID method. The findings demonstrate that the carbon emissions trading system can effectively decrease the total carbon emissions in pilot cities in China, and has a positive spatial spillover effect on neighboring cities of the pilot areas. The carbon emission trading system primarily reduces carbon emission by incentivizing businesses to implement eco-friendly practices and improve the industrial structure of pilot cities. Increased financial marketisation can promote the carbon emission reduction effects of the trading system. The impact of the carbon emission trading system on old industrial base cities and inland cities is more significant than those on non-old industrial base cities and coastal cities.

12.
ChemMedChem ; 17(4): e202100681, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34855308

RESUMO

In this study, we designed and synthesized twelve bitopic ligands as dopamine D2 receptor (D2 R) agonists. The forskolin-induced cAMP accumulation assay revealed that all the finial compounds are able to activate D2 R. Furthermore, bitopic ligand N-((trans)-4-(((2,3-dihydro-1H-inden-2-yl)(propyl)amino)methyl)cyclo-hexyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide (11 b) showed 21-fold higher potency than lead compound propyl aminoindane (2) and 17-fold higher subtype selectivity for D2 R over D4 R, indicating that the optimal length of spacer affects the D2 R functionality. Molecular modeling study exhibited that 11 b formed an electrostatic interaction and two H-bonds with amino acid Asp114, which contributes significantly to the D2 R functional activity. Taken together, we discovered a bitopic ligand 11 b as potent D2 R agonist, which may be used as a tool compound for further study.


Assuntos
Indanos/farmacologia , Piridinas/farmacologia , Receptores de Dopamina D2/agonistas , Células Cultivadas , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Indanos/química , Ligantes , Modelos Moleculares , Estrutura Molecular , Piridinas/síntese química , Piridinas/química , Relação Estrutura-Atividade
13.
Cancers (Basel) ; 14(19)2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36230714

RESUMO

Tumor metastasis occurs in lung cancer, resulting in tumor progression and therapy failure. Anoikis is a mechanism of apoptosis that combats tumor metastasis; it inhibits the escape of tumor cells from the native extracellular matrix to other organs. Deciphering the regulators and mechanisms of anoikis in cancer metastasis is urgently needed to treat lung cancer. Several natural and synthetic products exhibit the pro-anoikis potential in lung cancer cells and in vivo models. These products include artonin E, imperatorin, oroxylin A, lupalbigenin, sulforaphane, renieramycin M, avicequinone B, and carbenoxolone. This review summarizes the current understanding of the molecular mechanisms of anoikis regulation and relevant regulators involved in lung cancer metastasis and discusses the therapeutic potential of targeting anoikis in the treatment of lung cancer metastasis.

14.
Open Med (Wars) ; 16(1): 419-427, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33758783

RESUMO

FGF16 is implicated in the progression of some specific types of cancers, such as embryonic carcinoma, ovarian cancer, and liver cancer. Yet, the function of FGF16 in the development of lung cancer remains largely unexplored. In this study, we present the novel function of FGF16 and the regulation of miR-520b on FGF16 in lung cancer progression. In clinical lung cancer tissues, FGF16 is overexpressed and its high level is negatively associated with the low level of miR-520b. Furthermore, both the transcription and translation levels of FGF16 are restrained by miR-520b in lung cancer cells. For the regulatory mechanism investigation, miR-520b is able to directly bind to the 3'-untranslated region (3'UTR) of FGF16 mRNA, leading to its mRNA cleavage in the cells. Functionally, miR-520b reduces the growth of lung cancer and its inhibitor anti-miR520b is able to promote the growth through competing endogenous miR-520b. Moreover, FGF16 silence using RNA interference is capable of doing great damage to anti-miR-520b-accelerated growth of lung cancer. Thus, our finding indicates that FGF16 is a new target gene of miR-520b in lung cancer. For lung cancer, FGF16 may serve as a novel biomarker and miR-520b/FGF16 may be useful in clinical treatment.

15.
J Hazard Mater ; 412: 124407, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33548790

RESUMO

Exploring high-performance sensors for toxic arsenic detection is highly desired because of its great threat to the environment. Herein, we report a ratiometric fluorescent biosensor based on acid phosphatase and hemin loaded multifunctional Zn-based metal-organic framework (ACP/hemin@Zn-MOF) for high-performance arsenate (As(Ⅴ)) sensing. ACP/hemin@Zn-MOF is constructed by self-assembly, where hemin exhibits peroxidase-like activity and 2-aminoterephthalic acid ligand endows ACP/hemin@Zn-MOF with an intrinsic fluorescence (452 nm). When ACP/hemin@Zn-MOF catalyzes the oxidation of o-phenylenediamine (OPD), fluorescent 2,3-diaminophenazine (DAP) with an emission signal (564 nm) is produced and weakens ACP/hemin@Zn-MOF intrinsic fluorescence (452 nm) due to inner filter effect; after adding ascorbic acid 2-phosphate (AAP), ACP can hydrolyze AAP and produce ascorbic acid, which competitively suppresses the oxidation of OPD, resulting in the decrease of DAP signal (564 nm) and the recovery of ACP/hemin@Zn-MOF signal (452 nm); when As(V) is added, it irreversibly poisons ACP against hydrolyzing AAP, and the fluorescence signal at 564 nm recovers and the one at 452 nm is suppressed again. High-sensitivity and high-selectivity detection of As(V) (3.33-300 µg L-1) is realized, with a detection limit of 1.05 µg L-1. The biosensor was also successfully employed to detect total arsenic and As(V) in rice.

17.
Medicine (Baltimore) ; 97(20): e10754, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29768356

RESUMO

RATIONALE: Metastases of breast carcinoma to the main bronchus and choroid are rare, but have been reported in relevant literature. Late distant recurrence of breast carcinoma after more than 20 years is extremely rare. Herein, we report a 57-year-old woman with late distant recurrence and metastasis to the main bronchus and choroid almost 28 years after surgery. PATIENT CONCERNS: At the age of 29, the patient underwent chemotherapy and endocrine treatment after a right side mastectomy to remove breast carcinoma. The patient was hospitalized for a cough with blood-tinged sputum, dysphagia, and blurred vision in the left eye at the age of 57. DIAGNOSES: On evaluation, laboratory findings detected the elevated serum tumor markers of CA12-5, CA15-3, NSE, and Cyfra21-1. The imaging showed left lung metastase, multiple lymph node metastases, and small suspected metastases in the both sides of parietal lobes. Fundus fluorescein angiography showed choroidal occupying lesion of the left side which indicates secondary metastasis and retinal detachment. Combined with the pathological finding via fiberoptic bronchoscopic biopsy, the patient was clinically diagnosed with a late distant recurrence of breast carcinoma. INTERVENTIONS: The patient received oral endocrine therapy of letrozole, but she refused chemotherapy, radiotherapy and other topical treatments. OUTCOMES: At the 3-month follow-up visit, the multiple lesions of the left lung and lymph nodes had partially regressed, and the lesion of right parietal lobe had disappeared. The patient's clinical symptoms, such as blood-tinged sputum and dysphagia, had significantly improved. LESSONS: We have described this case and reviewed the relevant literature concerning late distant recurrence of breast carcinoma. Importantly, this case indicates that patients with HR positive breast carcinoma are more likely to develop late distant recurrence and clinicians should not ignore the follow-up examinations even more than 20 years after the surgery.


Assuntos
Neoplasias da Mama , Neoplasias Brônquicas , Neoplasias da Coroide , Efeitos Adversos de Longa Duração , Mastectomia/efeitos adversos , Nitrilas/administração & dosagem , Triazóis/administração & dosagem , Antineoplásicos/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Biópsia/métodos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Brônquios/diagnóstico por imagem , Brônquios/patologia , Neoplasias Brônquicas/patologia , Neoplasias Brônquicas/secundário , Broncoscopia/métodos , Corioide/diagnóstico por imagem , Corioide/patologia , Neoplasias da Coroide/patologia , Neoplasias da Coroide/secundário , Feminino , Angiofluoresceinografia/métodos , Humanos , Letrozol , Efeitos Adversos de Longa Duração/tratamento farmacológico , Efeitos Adversos de Longa Duração/patologia , Metástase Linfática/patologia , Mastectomia/métodos , Pessoa de Meia-Idade , Receptores de Estrogênio/análise , Receptores de Estrogênio/antagonistas & inibidores , Resultado do Tratamento
18.
J Tissue Eng Regen Med ; 8(6): 442-53, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22674864

RESUMO

We have previously reported a natural, human cartilage ECM (extracellular matrix)-derived three-dimensional (3D) porous acellular scaffold for in vivo cartilage tissue engineering in nude mice. However, the in vivo repair effects of this scaffold are still unknown. The aim of this study was to further explore the feasibility of application of cell-loaded scaffolds, using autologous adipose-derived stem cells (ADSCs), for cartilage defect repair in rabbits. A defect 4 mm in diameter was created on the patellar groove of the femur in both knees, and was repaired with the chondrogenically induced ADSC-scaffold constructs (group A) or the scaffold alone (group B); defects without treatment were used as controls (group C). The results showed that in group A all defects were fully filled with repair tissue and at 6 months post-surgery most of the repair site was filled with hyaline cartilage. In contrast, in group B all defects were partially filled with repair tissue, but only half of the repair tissue was hyaline cartilage. Defects were only filled with fibrotic tissue in group C. Indeed, histological grading score analysis revealed that an average score in group A was higher than in groups B and C. GAG and type II collagen content and biomechanical property detection showed that the group A levels approached those of normal cartilage. In conclusion, ADSC-loaded cartilage ECM scaffolds induced cartilage repair tissue comparable to native cartilage in terms of mechanical properties and biochemical components.


Assuntos
Tecido Adiposo/citologia , Cartilagem/patologia , Matriz Extracelular/química , Transplante de Células-Tronco , Células-Tronco/citologia , Alicerces Teciduais/química , Cicatrização , Animais , Fenômenos Biomecânicos , Cartilagem/cirurgia , Cartilagem/ultraestrutura , Adesão Celular , Células Cultivadas , Condrogênese , Colágeno Tipo II/metabolismo , Matriz Extracelular/ultraestrutura , Humanos , Camundongos , Coelhos , Medicina Regenerativa , Coloração e Rotulagem
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