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1.
Medicine (Baltimore) ; 99(19): e20081, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384478

RESUMO

INTRODUCTION: S-1, a new oral fluorouracil chemotherapeutical drug, has been increasingly used in clinical maintenance after first-line chemotherapy for stage III or IV gastric carcinoma (GC) and colorectal carcinoma (CRC) for its own advantages. XiangshaLiujunzi Decoction (XSLJZD), a classic traditional Chinese medicine (TCM) formula with effects of alleviating the adverse reactions of chemotherapy and improving the quality of life of cancer patients has been gradually confirmed, with no more reports about the maintenance therapy mode of combination of chemotherapeutic drugs and TCM. We designed the study of XSLJZD combined with S-1 in the maintenance therapy of Stage III or IV GC and CRC, and hoped that this research program will go further and comprehensively evaluate its efficacy and safety. OBJECTIVES: The aim of this study was to determine the efficacy and safety of XSLJZD combined with S-1 in the maintenance therapy of stage III or IV GC and CRC. METHODS: This study is an open, single-center, randomized study. Patients with stage III or stage IV GC and CRC will be randomized (1:1) into S-1group, S-1 combined with XSLJZD group for 5 years of maintenance therapy. The primary endpoint was progression-free survival, and secondary end point was overall survival and Quality of Life Assessment (QOLA), which include an improvement in symptoms before and after treatment, Karnofsky Performance Status, and adverse events assessment. DISCUSSION: This study will provide meaningful clinical information about the combination of chemotherapeutic drugs S-1 with TCM in the maintenance therapy of stage III or IV GC and CRC. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-INR-16008575.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Quimioterapia de Manutenção , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Tegafur/administração & dosagem , Neoplasias Colorretais/patologia , Combinação de Medicamentos , Humanos , Estadiamento de Neoplasias , Fitoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/patologia , Resultado do Tratamento
2.
Br J Cancer ; 122(3): 372-381, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31776458

RESUMO

BACKGROUND: Most gastrointestinal stromal tumours (GIST) are driven by activating oncogenic mutations of KIT/PDGFRA, which provide a compelling therapeutic target. Our previous studies showed that CDC37, regulated by casein kinase 2 (CK2), is a crucial HSP90 cofactor for KIT oncogenic function and a promising and more selective therapeutic target in GIST. METHODS: Biologic mechanisms of CK2-mediated CDC37 regulation were assessed in GISTs by immunoblotting, immunoprecipitations, knockdown and inactivation assays. The effects of a combination of KIT and CK2 inhibition were assessed by immunoblotting, cell viability, colony growth, cell cycle analysis, apoptosis, migration and invasiveness. RESULTS: CK2 overexpression was demonstrated by immunoblotting in GIST cell lines and patient biopsies. Treatment with a specific CK2 inhibitor, CX4945, leads to CDC37 dephosphorylation and inhibits KIT signalling in imatinib-sensitive and in imatinib-resistant GIST cell lines. Immunoprecipitation demonstrated that CK2 inhibition blocks KIT:HSP90:CDC37 interaction in GIST cells. Coordinated inhibition of CK2 and KIT by CX4945 (or CK2 shRNA) and imatinib, respectively, leads to increased apoptosis, anti-proliferative effects and cell cycle arrest and decreased p-AKT and p-S6 expression, migration and invasiveness in all GIST cell lines compared with either intervention alone, indicating additive effects of inhibiting these two important regulators of GIST biology. CONCLUSION: Our findings suggest that combinatorial inhibition of CK2 and KIT warrants evaluation as a novel therapeutic strategy in GIST, especially in imatinib-resistant GIST.

3.
Cell Cycle ; 18(24): 3472-3490, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31713447

RESUMO

Protein kinase CK2 alpha (CK2α) is involved in the development of multiple malignancies. Overexpression of Y-box binding protein 1 (YBX1) is related to tumor proliferation, drug resistance, and poor prognosis. Studies have demonstrated that both CK2 and YBX1 could regulate the PI3K/AKT pathway. In addition, we predicted that CK2 might be the upstream kinase of YBX1 through the Human Protein Reference Database (HPRD). Herein, we hypothesize that CK2 may interact with YBX1 and they regulate the PI3K/AKT signaling pathway together. Expressions of CK2α and YBX1 in cancer cell lines were evaluated by immunoblotting. The results showed that CK2α could regulate the expression of YBX1 at the transcriptional level, which is dependent on its enzymatic activity. Synergistic effects of PI3K/AKT pathway inactivation could be observed through combined inhibition of CK2α and YBX1, and YBX1 was required for CK2α-induced PI3K/AKT pathway activation. Further results demonstrated that CK2α could interact with YBX1 and PI3K/AKT antagonist decreased cell resistance to doxorubicin induced by co-activation of CK2α and YBX1. These results indicated that combined inhibition of CK2α and YBX1 showed synergistic effects in inactivating the PI3K/AKT signaling pathway and may be one of the mechanisms involved in tumor growth and migration.

4.
Oncogene ; 38(39): 6615-6629, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31371779

RESUMO

Oncogenic KIT or PDGFRA tyrosine kinase mutations are compelling therapeutic targets in most gastrointestinal stromal tumors (GISTs), and the KIT inhibitor, imatinib, is therefore standard of care for patients with metastatic GIST. However, some GISTs lose expression of KIT oncoproteins, and therefore become KIT-independent and are consequently resistant to KIT-inhibitor drugs. We identified distinctive biologic features in KIT-independent, imatinib-resistant GISTs as a step towards identifying drug targets in these poorly understood tumors. We developed isogenic GIST lines in which the parental forms were KIT oncoprotein-dependent, whereas sublines had loss of KIT oncoprotein expression, accompanied by markedly downregulated expression of the GIST biomarker, protein kinase C-theta (PRKCQ). Biologic mechanisms unique to KIT-independent GISTs were identified by transcriptome sequencing, qRT-PCR, immunoblotting, protein interaction studies, knockdown and expression assays, and dual-luciferase assays. Transcriptome sequencing showed that cyclin D1 expression was extremely low in two of three parental KIT-dependent GIST lines, whereas cyclin D1 expression was high in each of the KIT-independent GIST sublines. Cyclin D1 inhibition in KIT-independent GISTs had anti-proliferative and pro-apoptotic effects, associated with Rb activation and p27 upregulation. PRKCQ, but not KIT, was a negative regulator of cyclin D1 expression, whereas JUN and Hippo pathway effectors YAP and TAZ were positive regulators of cyclin D1 expression. PRKCQ, JUN, and the Hippo pathway coordinately regulate GIST cyclin D1 expression. These findings highlight the roles of PRKCQ, JUN, Hippo, and cyclin D1 as oncogenic mediators in GISTs that have converted, during TKI-therapy, to a KIT-independent state. Inhibitors of these pathways could be effective therapeutically for these now untreatable tumors.


Assuntos
Ciclina D1/fisiologia , Tumores do Estroma Gastrointestinal/genética , Proteínas Proto-Oncogênicas c-kit/genética , Antineoplásicos/uso terapêutico , Proliferação de Células/fisiologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/metabolismo , Humanos , Proteína Quinase C-theta/fisiologia , Inibidores de Proteínas Quinases/uso terapêutico
5.
J Biol Chem ; 2019 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-30728243

RESUMO

This article has been withdrawn by the authors. Some of the SDHA enzyme activity data were flawed and were not performed and analyzed correctly. The withdrawing authors are in the process of correcting the data and re-evaluating them for resubmission.

6.
Oncol Lett ; 17(2): 2020-2030, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30675269

RESUMO

Receptor tyrosine kinase (RTK) anaplastic lymphoma kinase (ALK) serves a crucial role in brain development. ALK is located on the short arm of chromosome 2 (2p23) and exchange of chromosomal segments with other genes, including nucleophosmin (NPM), echinoderm microtubule-associated protein-like 4 (EML4) and Trk-fused gene (TFG), readily occurs. Such chromosomal translocation results in the formation of chimeric X-ALK fusion oncoproteins, which possess potential oncogenic functions due to constitutive activation of ALK kinase. These proteins contribute to the pathogenesis of various hematological malignancies and solid tumors, including lymphoma, lung cancer, inflammatory myofibroblastic tumors (IMTs), Spitz tumors, renal carcinoma, thyroid cancer, digestive tract cancer, breast cancer, leukemia and ovarian carcinoma. Targeting of ALK fusion oncoproteins exclusively, or in combination with ALK kinase inhibitors including crizotinib, is the most common therapeutic strategy. As is often the case for small-molecule tyrosine kinase inhibitors (TKIs), drug resistance eventually develops via an adaptive secondary mutation in the ALK fusion oncogene, or through engagement of alternative signaling mechanisms. The updated mechanisms of a variety of ALK fusions in tumorigenesis, proliferation and metastasis, in addition to targeted therapies are discussed below.

7.
J Cell Biochem ; 120(4): 5713-5721, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30362602

RESUMO

BACKGROUNDS AND AIMS: Increased arterial stiffness may increase cardiovascular morbidity and mortality. Angiotensin II type 1 receptor blocker losartan is potentially useful in controlling the central blood pressure and arterial stiffness in mild to moderate essential hypertension, while the effects of losartan in aged patients with essential hypertension are not entirely investigated. METHODS: The carotid-femoral arterial pulse wave velocity (PWV) was measured in aged patients with essential hypertension. RESULTS: In a cross-sectional study, PWV value was significantly higher in these old patients with essential hypertension, compared with patients without essential hypertension. Logistic regression analysis indicated that age, hypertension duration, and losartan treatment are risk factors of arterial stiffness. In a perspective study, long-term administration of losartan (50 mg/d) remarkably reduced PWV in aged patients with essential hypertension. In a longitudinal study, PWV is an independent predictor of the occurrence of acute coronary syndrome (ACS) in elderly patients with essential hypertension by using multivariate analysis. Further, the ACS occurrence was reduced by long-term administration of losartan in aged patients with essential hypertension, compared with the old hypertensive patients without taking losartan. CONCLUSION: Losartan treatment is a negative risk factor of arterial stiffness and reduces the risk of ACS in aged patients with essential hypertension.

8.
J Cell Biochem ; 120(3): 3790-3800, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30367511

RESUMO

BACKGROUND: Atherosclerosis is a chronical inflammatory disease in arterial walls, which is involved in oxidative stress and endothelial dysfunction. Aromatherapy is one of the complementary therapies that use essential oils as the major therapeutic agents to treat several diseases. Citronellal (CT) is a monoterpene predominantly formed by the secondary metabolism of plants, producing antithrombotic, antiplatelet, and antihypertensive activities. AIM: The aim of the present study is to explore whether aromatherapy with CT improves endothelial function to prevent the formation of atherosclerotic plaque in vivo. METHODS: An AS model in carotid artery was induced by balloon injury and vitamin D3 injection in rats fed with a high-fat diet. The size of the carotid atherosclerotic plaque was determined by ultrasound, oil red, and hematoxylin-eosin staining. Endothelial function was assessed by measuring acetylcholine-induced vessel relaxation in an organ chamber. RESULTS: Administrations of CT (50, 100, and 150 mg/kg) as well as lovastatin dramatically reduced the size of carotid atherosclerotic plaque in rats in a dose-dependent manner, compared with atherosclerotic rats fed with a high-fat diet plus balloon injury and vitamin D3. Mechanically, CT improved endothelial dysfunction, increased cell migration, and suppressed oxidative stress and inflammation in vascular endothelium in rats feeding on the high-fat diet plus balloon injury. Further, CT downregulated the protein levels of sodium-hydrogen exchanger 1 in rats with atherosclerosis. CONCLUSION: CT improves endothelial dysfunction and prevents the growth of atherosclerosis in rats by reducing oxidative stress. Clinically, CT is potentially considered as a medicine to treat patients with atherosclerosis.

9.
Cell Cycle ; 17(23): 2577-2592, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30488756

RESUMO

Oncogenic KIT or PDGFRA receptor tyrosine kinase (TK) mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GISTs), and the KIT/PDGFRA kinase inhibitor, imatinib, is the standard of care for patients with metastatic GIST. However, approximately 10% of KIT-positive GIST metastases lose KIT expression at the time of clinical progression during imatinib therapy. In the present report, we performed TK-activation screens, using phosphotyrosine-TK double immunoaffinity purification and mass spectrometry, in GIST in vitro models lacking KIT expression. These studies demonstrated tyrosine-phosphorylated EGFR, AXL, and EPHA2 in four of six KIT-negative GIST lines (GIST62, GIST522, GIST54, GIST226, GIST48B, and GIST430B), and tyrosine-phosphorylated focal adhesion kinase (FAK) in each of the six KIT-negative lines. AXL expression was strong in KIT-negative or -weak clinical GIST samples that were obtained from progressing metastases during imatinib therapy. AXL knockdown inhibited viability in three KIT-negative GIST cell lines (GIST62, GIST54, and GIST522), but not in an AXL-negative, KIT-positive GIST control cell line (GIST430). AXL inhibition by R428, a specific AXL kinase inhibitor, reduced viability in AXL-activated GIST54. AXL knockdown in GIST62, GIST522, and GIST54 was accompanied by an increase in p21, p27, and p53 expression. By contrast, gefitinib-mediated EGFR inhibition, PF562271-mediated FAK inactivation, and shRNA-mediated knockdowns of EPHA2 and FAK had no effect on viability or colony formation of the KIT-negative GISTs. These findings highlight the potential relevance of AXL/p53 signaling as a therapeutic target in a subset of GISTs that have lost KIT oncoprotein expression.


Assuntos
Proteínas Proto-Oncogênicas c-kit/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/antagonistas & inibidores , Proteína-Tirosina Quinases de Adesão Focal/genética , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Gefitinibe/farmacologia , Humanos , Mesilato de Imatinib/farmacologia , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptor EphA2/antagonistas & inibidores , Receptor EphA2/genética , Receptor EphA2/metabolismo
10.
Ying Yong Sheng Tai Xue Bao ; 29(10): 3175-3182, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30325140

RESUMO

With the continuous drought stress treatment to five Hydrangea macrophylla varieties of different abilities of drought resistance, twenty-five physiological-biochemical indices were mea-sured. We evaluated the drought resistance of different varieties and established the mathematic model. The results showed that leaf mass per area, cell membrane permeability (CMP), the content of malonaldehyde (MDA), the activity of superoxide dismutase (SOD), soluble sugar content, proline content, intercellular carbon dioxide and non-photochemical quenching coefficient were significantly increased under drought stress for twenty days. In contrast, relative water content, net photosynthetic rate, stomatal conductance, transpiration rate, actual photochemical efficiency of PS2 and electron transport rate (ETR) were significantly decreased. The principal component analysis classified those indices into three independent comprehensive indices (accumulative contribution of 87.1%). The principal component 1 mainly reflected the information of photosynthetic and fluorescence. The principal component 2 mainly reflected the information of plant vigor. The principal component 3 mainly reflected the information of membrane system and osmotic adjust system. Five H. macrophylla varieties were divided into three categories by clustering analysis: drought-tolerant type (including H. macrophylla 'Lavblaa') and H. macrophylla 'Taube'), intermediate type (H. macrophylla 'You and me romance'), and drought-intolerant type (including H. macrophylla cv. Endless summer bride and H. macrophylla 'Tricolor'). Comprehensive evaluation of drought resis-tance (D value) showed that the ability of drought resistance decreased in order of H. macrophylla 'Lavblaa' > H. macrophylla 'Taube'> H. macrophylla 'You and me romance'> H. macrophylla cv. Endless summer bride > H. macrophylla 'Tricolor'. Four influential indices for drought resis-tance including CMP, the activity of peroxidase (POD), soluble protein contents (SP) and ETR was screened by stepwise regression analysis, which could be used for the rapid identification of drought resistance of H. macrophylla.


Assuntos
Hydrangea , Dióxido de Carbono , Secas , Transporte de Elétrons , Malondialdeído , Fotossíntese , Folhas de Planta , Estresse Fisiológico , Superóxido Dismutase , Água
11.
J Cancer Res Clin Oncol ; 144(11): 2097-2106, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30073421

RESUMO

PURPOSE: Lung cancer and mesothelioma are two types of respiratory disease that have fatal courses and poor prognoses. Although a substantial number of targeted small molecules and antibody drugs have been developed, the 5-year survival rates of these patients remain relatively low. Moreover, most patients inevitably develop clinical resistance to treatment. Therefore, novel therapeutic options and cancer prognostic biomarkers are urgently needed. METHODS: In this review, we summarized the recent literature from various electronic databases, including PubMed, and highlighted the most advanced findings regarding the hippo pathway in lung cancer and mesothelioma. CONCLUSION: The hippo signaling transduction pathway has been demonstrated to play crucial roles in lung cancer and mesothelioma pathogenesis, including tumor development and multidrug resistance, and is emerging as a promising therapeutic target, potentially providing new tools for the detection of these tumors at an early stage.


Assuntos
Neoplasias Pulmonares/metabolismo , Mesotelioma/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mesotelioma/patologia , Mesotelioma/terapia , Proteínas Supressoras de Tumor/metabolismo
12.
Am J Ophthalmol ; 195: 1-7, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30053479

RESUMO

PURPOSE: To assess differences in clinical and demographic characteristics between glaucoma patients identified by community screening and those newly diagnosed in hospital in a Chinese setting. DESIGN: Prospective comparative cohort study. METHODS: A total of 373 patients identified with glaucoma among 27 000 persons undergoing community screening were enrolled as the Screening group. The Clinic group consisted of 119 consecutively presenting, newly diagnosed glaucoma patients in hospital. Primary outcomes were mean deviation (MD), visual field index (VFI) and pattern standard deviation (PSD) on Humphrey Field Analyzer, and intraocular pressure (IOP). Disease severity was categorized into 5 stages based on MD. RESULTS: A total of 89.6% (328/373) of Screening group patients had IOP < 21 mm Hg, compared to 48.7% (58/119) in the Clinic group (P < .001). The mean VFI, MD, and PSD were 76.4% ± 23.8%, -9.7 ± 7.3 dB, and 6.4 ± 3.4 dB in the Screening group and significantly worse in the Clinic group: 44.1% ± 32.0%, -19.8 ± 9.5 dB, and 7.6 ± 3.1 dB (P < .001 for MD and VFI, P = .001 for PSD). Nearly three quarters of Screening patients had early or moderate visual field loss (monocular), while nearly half of Clinic patients had severe loss at the time of diagnosis. Screening patients were significantly more likely to be older (P < .001) and female (P < .001) than Clinic patients. CONCLUSION: Glaucoma patients detected through community screening had significantly milder damage, and were more likely to include underserved groups (women, elderly) than those newly diagnosed in a clinic in this setting. Comparison with population studies suggests that cases of glaucoma with IOP < 21 mm Hg are severely underascertained in China, a situation that may be improved by screening.


Assuntos
Serviços de Saúde Comunitária/estatística & dados numéricos , Glaucoma/diagnóstico , Glaucoma/epidemiologia , População Urbana/estatística & dados numéricos , Idoso , China/epidemiologia , Feminino , Glaucoma/terapia , Humanos , Pressão Intraocular/fisiologia , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/diagnóstico , Hipertensão Ocular/epidemiologia , Hipertensão Ocular/terapia , Estudos Prospectivos , Índice de Gravidade de Doença , Tonometria Ocular , Testes de Campo Visual , Campos Visuais/fisiologia
13.
Int J Mol Med ; 42(1): 131-140, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29620145

RESUMO

Leukemia inhibitory factor (LIF) is the most pleiotropic cytokine of the interleukin­6 family, and is widely used to establish and maintain pluripotent stem cells, particularly mouse pluripotent stem cells. However, no reports have fully elucidated the application of LIF in marmoset induced pluripotent stem cell (iPSC) culture, particularly the underlying mechanisms. To demonstrate the feasibility of the application of LIF to marmoset iPSCs, the present study assessed these cells in the presence of LIF. Cell proliferation was measured using MTT assay, cell apoptosis was determined by flow cytometric analysis of fluorescein isothiocyanate Annexin V staining and the differentially expressed genes were analysed using Digital Gene Expression (DGE) analysis. The altered expression of pluripotency­associated genes was confirmed by reverse transcription­quantitative polymerase chain reaction and western blot analysis. Furthermore, following treatment with LY294002, cell proliferation was measured by MTT assay and protein levels were confirmed by western blot analysis. The results showed that LIF significantly promoted the number of proliferating cells, but had no effect on apoptosis. Digital Gene Expression analysis was used to examine the differentially expressed genes of marmoset iPSCs in the presence of LIF. The results showed that the pluripotency­associated transcription factor­encoding gene T­box 3 (Tbx­3) was activated by LIF. Notably, LIF increased the levels of phosphorylated (p­)AKT and Tbx­3 in the marmoset iPSCs. Furthermore, pretreatment with LY294002, an inhibitor of phosphoinositide 3­kinase (PI3K), significantly impaired the LIF­induced upregulation of p­AKT and Tbx­3 in the marmoset iPSCs, suggesting that the PI3K/Akt signaling pathway is involved in this regulation. Taken together, the results suggested that LIF is effective in maintaining marmoset iPSCs in cultures, which is associated with the activation of Tbx­3 through regulation of the PI3K/Akt signaling pathway.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/enzimologia , Fator Inibidor de Leucemia/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteínas com Domínio T/metabolismo , Animais , Apoptose/efeitos dos fármacos , Callithrix , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , Camundongos , Modelos Biológicos , Transdução de Sinais/efeitos dos fármacos , Proteínas com Domínio T/genética
14.
Food Res Int ; 106: 446-457, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29579946

RESUMO

Xiebai is an edible Chinese herb with various health and therapeutic benefits. To evaluate its nutritional and health values, the free amino acids and derivatives of its two botanical origins (i.e., Allium chinense G. Don and Allium macrostemon Bunge) were isolated using a solvent extraction method and analyzed using automatic amino acid analysis and ultra-performance liquid chromatography-quadrupole-time of flight (UPLC-Q-TOF) mass spectrometry. Our data show that both plants contain abundant free amino acids, and the amount of total free amino acids in A. chinense G. Don is higher than that in A. macrostemon Bunge. The free amino acid compositions in the two plants are qualitatively similar, including nineteen proteinogenic and four non-proteinogenic amino acids. The identified proteinogenic amino acids include eight essential amino acids and five semi-essential amino acids. The sum of essential and semi-essential amino acids accounts for 64.9% and 69.7% of the total free amino acids of the two plants, respectively. The principal amino acids of both plants, from highest concentration to lowest concentration, are arginine, glutamine, glutamic acid, asparagine and serine. A. chinense G. Don is also rich in citrulline and lysine. In addition, two amino acid derivatives were identified from the two plants, i.e., the proline analog N­methyl­proline and the dipeptide H-Glu-Tyr-OH. For the first time, the presence of N­methyl­proline in the plants of the Allium genus and the presence of H-Glu-Tyr-OH in unprocessed food sources are reported. The influences of the identified substances on the flavor, nutrition and health values of Xiebai are discussed.


Assuntos
Allium/química , Aminoácidos/análise , Raízes de Plantas/química , Plantas Comestíveis/química , Análise de Alimentos/métodos , Valor Nutritivo , Paladar
15.
Stem Cell Res Ther ; 9(1): 49, 2018 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-29482598

RESUMO

BACKGROUND: Induced pluripotent stem cells (iPS) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). Mφ show great promise in disease pathogenesis, particularly tuberculosis. However, there is no information about human iPS-derived (hiPS) macrophages (hiPS-Mφ) in response to tuberculosis infection. METHODS: In the present study, macrophages derived from hiPS were established via embryoid body (EB) formation by using feeder-free culture conditions, and the human monocyte cell line THP-1 (THP-1-Mφ) was used as control. iPS-Mφ were characterized by using morphology, Giemsa staining, nonspecific esterase staining (α-NAE), phagocytosis, and surface phenotype. Additionally, after treatment with Bacillus Calmette-Guérin (BCG) for 24 h, cell apoptosis was detected by using an Annexin V-FITC Apoptosis Detection assay. The production of nitric oxide (NO), expression of tumor necrosis factor alpha (TNF-α), activity of apoptosis-related protein cysteine-3 (Caspase-3) and expression of B-cell lymphoma-2 (Bcl-2) were analyzed. RESULTS: With respect to morphology, surface phenotype, and function, the iPS-Mφ closely resembled their counterparts generated in vitro from a human monocyte cell line. iPS-Mφ exhibited the typically morphological characteristics of macrophages, such as round, oval, fusiform and irregular characteristics. The cells were Giemsa-stained-positive, α-NAE-positive, and possessed phagocytic ability. iPS-Mφ express high levels of CD14, CD11b, CD40, CD68, and major histocompatibility complex II (MHC-II). Moreover, with regard to the apoptotic rate, the production of NO, expression of TNF-α, and activity of Caspase-3 and Bcl-2, iPS-Mφ closely resemble that of their counterparts generated in vitro from human monocyte cell line in response to BCG infection. The rate of apoptosis of BCG-treated iPS-Mφ was 37.77 ± 7.94% compared to that of the untreated group at 4.97 ± 1.60% (P < 0.01) by using Annexin V-FITC Apoptosis Detection. Additionally, the rate of apoptosis of BCG-treated THP-1-Mφ was 37.1 ± 2.84% compared to that of the untreated group at 6.19 ± 1.68% (P < 0.001). The expression of TNF-α and the production of NO were significantly increased (P < 0.001), and the activity of Caspase-3 was increased. However, the expression of Bcl-2 was inhibited (P < 0.001). CONCLUSIONS: Our results demonstrate that Mφ derived from hiPS perform the immunological function in response to Bacillus Calmette-Guérin infection by undergoing apoptosis, increasing the production of NO and expression of TNF-α. Thus, our study may help to overcome the limitations of research into certain rare diseases due to the lack of adequate supply of disease-specific primary cells.


Assuntos
Apoptose/imunologia , Regulação da Expressão Gênica/imunologia , Células-Tronco Pluripotentes Induzidas/imunologia , Macrófagos/imunologia , Mycobacterium bovis/imunologia , Óxido Nítrico/imunologia , Tuberculose/imunologia , Fator de Necrose Tumoral alfa/imunologia , Humanos , Células-Tronco Pluripotentes Induzidas/microbiologia , Células-Tronco Pluripotentes Induzidas/patologia , Macrófagos/microbiologia , Macrófagos/patologia , Células THP-1 , Tuberculose/microbiologia , Tuberculose/patologia
16.
Oncol Lett ; 15(1): 545-551, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29375719

RESUMO

Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3) serves a role in the progression and prognosis of cancer. PHD3 is able to induce apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and HIF2α were analyzed by western blot analysis and immunohistochemistry in 84 paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver tissues. The mRNA levels of PHD3 and HIF2α were analyzed by reverse transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The high level of expression of PHD3 in HCC tissues was associated with good differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition, HIF2α expression was lower in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.002; immunohistochemistry positive rate: P=0.002). No statistically significant associations were identified between HIF2α expression and clinicopathological characteristics. Pearson's and Spearman's correlation coefficients revealed no correlation between HIF2α and PHD3 expression in HCC. In conclusion, PHD3 expression acts as a favorable prognostic marker for patients with HCC. There is no correlation between PHD3 and HIF2α expression in HCC.

17.
Polymers (Basel) ; 10(12)2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30961277

RESUMO

The addition of salt to a colloid solution ensures that emulsions can be easily separated into two phases and that polymer latexes can be coagulated. The switchable stability of emulsions and polymer latexes would improve the properties for their current applications. A switchable process of salt addition can be achieved using CO2 and switchable water, and it is a novel, benign approach to achieving a switchable ionic strength in an aqueous solution. However, the problem associated with switchable water is that its additives are all synthetic tertiary amines, most of which are harmful to human beings and the environment. Oligochitosan, as a natural product, can also be used as a switchable water additive. In this paper, a new switchable water system using oligochitosan to change the ionic strength was explored for use in several potential industrial applications. The conductivity of the aqueous solution of oligochitosan (0.2 wt.%) was switched from 0.2 to 331 µS/cm through the addition and removal of CO2. Oligochitosan and CO2 were successfully utilized to reversibly break a crude oil emulsion. Polystyrene (PS) latexes could also be reversibly destabilized; the zeta potential of the PS latex changed between -5.8 and -45.2 mV in the absence and presence of CO2 after oligochitosan was dissolved in the PS latex. The use of oligochitosan is a more environmentally friendly means for reversibly separating colloid solutions.

18.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(11): 1174-1179, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29132465

RESUMO

OBJECTIVE: To investigate the significance of flexible bronchoscopy in children with respiratory diseases. METHODS: A retrospective analysis was performed for the clinical data of 80 children who were hospitalized due to respiratory diseases (including severe pneumonia, Mycoplasma pneumoniae pneumonia with atelectasis/lung consolidation/local emphysema, protracted pneumonia, coughing and wheezing of unknown cause, chronic cough of unknown cause, and laryngeal stridor) and who underwent flexible bronchoscopy/alveolar lavage. RESULTS: Bronchoscopy found that all the 80 children had endobronchial inflammation, among whom 28 children had severe airway obstruction by secretion. Twenty-four children had congenital airway dysplasia besides endobronchial inflammation, and three children had bronchial foreign bodies. In the children with coughing and wheezing of unknown cause and laryngeal stridor, some had congenital airway dysplasia or bronchial foreign bodies. Among the 27 children with Mycoplasma pneumoniae pneumonia, 26 had severe airway obstruction/embolization by secretion; 25 children (93%) underwent chest imaging again at 2 weeks after alveolar lavage, and the results showed complete or partial lung recruitment. Among the 80 children who underwent bronchoscopy, 3 had severe hypoxemia during surgery, 1 had epistaxis, 1 had minor bleeding during alveolar lavage, 3 had transient bronchospasm, and 5 had postoperative fever; these children were all improved after symptomatic treatment. CONCLUSIONS: Flexible bronchoscopy is safe and reliable in children with respiratory diseases. Early alveolar lavage under a flexible bronchoscope is recommended for children with severe/refractory Mycoplasma pneumoniae pneumonia to improve prognosis. Flexible bronchoscopy is recommended for children with recurrent coughing and wheezing and persistent laryngeal stridor, in order to directly observe the throat and airway under an endoscope.


Assuntos
Broncoscopia/métodos , Pneumopatias/diagnóstico , Broncoscopia/efeitos adversos , Criança , Pré-Escolar , Tosse/diagnóstico , Feminino , Humanos , Lactente , Masculino , Pneumonia por Mycoplasma/diagnóstico , Sons Respiratórios/diagnóstico , Estudos Retrospectivos
19.
Cancer Res ; 77(18): 5107-5117, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28760855

RESUMO

Oncogenic KIT or PDGFRA receptor tyrosine kinase (RTK) mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GIST. Most GISTs eventually acquire imatinib resistance due to secondary mutations in the KIT kinase domain, but it is unclear whether these genomic resistance mechanisms require other cellular adaptations to create a clinically meaningful imatinib-resistant state. Using phospho-RTK and immunoblot assays, we demonstrate activation of KIT and insulin receptor (IR) in imatinib-resistant GIST cell lines (GIST430 and GIST48) and biopsies with acquisition of KIT secondary mutations, but not in imatinib-sensitive GIST cells (GIST882 and GIST-T1). Treatment with linsitinib, a specific IR inhibitor, inhibited IR and downstream intermediates AKT, MAPK, and S6 in GIST430 and GIST48, but not in GIST882, exerting minimal effect on KIT phosphorylation in these cell lines. Additive effects showing increased apoptosis, antiproliferative effects, cell-cycle arrest, and decreased pAKT and pS6 expression, tumor growth, migration, and invasiveness were observed in imatinib-resistant GIST cells with IR activation after coordinated inhibition of IR and KIT by linsitinib (or IR shRNA) and imatinib, respectively, compared with either intervention alone. IGF2 overexpression was responsible for IR activation in imatinib-resistant GIST cells, whereas IR activation did not result from IR amplification, IR mutation, or KIT phosphorylation. Our findings suggest that combinatorial inhibition of IR and KIT warrants clinical evaluation as a novel therapeutic strategy in imatinib-resistant GISTs. Cancer Res; 77(18); 5107-17. ©2017 AACR.


Assuntos
Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Gastrointestinais/tratamento farmacológico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Mesilato de Imatinib/farmacologia , Proteínas Proto-Oncogênicas c-kit/antagonistas & inibidores , Receptor de Insulina/antagonistas & inibidores , Animais , Antígenos CD , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/metabolismo , Tumores do Estroma Gastrointestinal/patologia , Humanos , Camundongos , Camundongos Nus , Fosforilação/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Medicine (Baltimore) ; 96(17): e6538, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28445255

RESUMO

RATIONALE: Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic syndrome characterized by a unique type of gastrointestinal hamartomatous polyp associated with oral and anal mucocutaneous pigmentations. Peutz-Jeghers polyps occur most numerously in the small intestine but frequently in the colon and stomach, only a few cases have been reported in the duodenum. PATIENT CONCERN: A further family history survey discovered 10 out of 14 members of the family (in 4 generations) had mucocutaneous pigmentations, but many of them were living in rural areas where they had no access to specialized medical services, so none were checked with endoscopy for polyps of hamartoma. DIAGNOSES: We report the case of a boy patient with mucocutaneous pigmentations over the lips, and a history of recurrent bouts of vomit and anemia over the preceding two years, no abdominal pain and mass. An upper gastrointestinal endoscopy revealed some small polyps in the stomach and multiple sessile polyps in the second part of the duodenum, but colonoscopy exam did not reveal any lesion. INTERVENTIONS: A double polypectomy and duodenum segmentary resection with end-to-end anastomosis was performed. Histopathology of the resected duodenum polyps indicated it to be a typical hamartomatous polyp. OUTCOMES: The child was under regular follow-up and recovered well. LESSONS: In this case, the patient was characteristic with pigmentations on his lips and intermittent upper intestinal obstruction (due to mass duodenal polyps), there are no definitive guidelines for the treatment to duodenal PJS hamartomatous polyp, each case requires tailor-made management.


Assuntos
Obstrução Intestinal/complicações , Síndrome de Peutz-Jeghers/complicações , Criança , Diagnóstico Diferencial , Humanos , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/patologia , Obstrução Intestinal/cirurgia , Masculino , Síndrome de Peutz-Jeghers/diagnóstico , Síndrome de Peutz-Jeghers/patologia , Síndrome de Peutz-Jeghers/cirurgia
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