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1.
J Am Soc Mass Spectrom ; 35(4): 674-682, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38416724

RESUMO

False changes discovered by quantitative proteomics reduce the trust of biologists in proteomics and limit the applications of proteomics to unlock biological mechanisms, which suppresses the application of proteomics techniques in the pharmaceutical industry more than it does in academic research. To remove false changes that arise during LC-MS/MS data acquisition, we evaluated the contributions of peptide abundance and number of unique peptides on reproducibility. Lower abundance and only one unique peptide have a higher risk of generating a higher coefficient of variation (CV), resulting in less accurate quantification. However, the abundance of peptides in samples is not adjustable and discarding proteins quantified by only one unique peptide is not a choice either. Indeed, a large percentage of proteins are accurately quantified by only one unique peptide. Therefore, to improve the calculations of the CV, we leverage a new function in PEAKS called QC-channels which enables technical replicates of each spectrum to be evaluated prior to calculation of the CV. While the QC-channels function in PEAKS significantly reduced the false quantification, random false changes still exist due to known or unknown reasons. To address this challenge, we present the idea of Trend-design to track trend changes rather than changes from two points to remove false quantifications and reveal consequential changes responding to a treatment or condition. The idea was confirmed by molecules with different affinity and dose in the current study. The combination of QC-channels and Trend-design enables a more impactful quantitative proteomics to allow unlocking biological mechanisms using proteomics.


Assuntos
Proteômica , Espectrometria de Massas em Tandem , Cromatografia Líquida/métodos , Proteômica/métodos , Reprodutibilidade dos Testes , Proteínas , Peptídeos/química
2.
J Phys Chem Lett ; 14(40): 9075-9081, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37788153

RESUMO

The search for lead-free perovskite materials has triggered intensive interest. Here, we study the electronic structures and optical properties of cation-deficient Ruddlesden-Popper oxysulfide perovskites Ln2Ti2O5S2 (Ln = Sc, Y, or La), with a tunable band gap of 1.45-2.1 eV and a small exciton binding energy of ∼0.1 eV, among which Y2Ti2O5S2 has been synthesized experimentally. Sc2Ti2O5S2 possesses the largest light absorbance in the visible region. We further rationalize the light absorption via the transition dipole moment and suggest potential applications of Sc2Ti2O5S2 in solar cells and Y2Ti2O5S2 and La2Ti2O5S2 in water splitting. In addition, this family exhibits small effective masses within the x-y plane and large ones along the z direction. Most importantly, electron gas-like carrier behaviors are observed within the Ti-O bond region, offering a diffusion channel for electron transport. These findings greatly advance our understanding of lead-free perovskites and offer a novel material platform for future optoelectronic devices.

3.
Nat Prod Res ; : 1-7, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37820042

RESUMO

A series of C21 steroidal glycosides were isolated from the root bark of Periploca sepium, including a new compound, perisepiumoside A1 (1), and six known compounds (2-7). Their structures were elucidated by analysis of HR-ESI-MS, and 1D and 2D NMR spectroscopic data. All these compounds were tested for their NO production inhibitory activity in LPS-stimulated RAW 264.7 cells. Results showed that these C21 steroidal glycosides could remarkably inhibit NO production, particularly 1 and 2 with IC50 values of 30.81 ± 0.18 µM and 44.39 ± 0.21 µM, respectively. In addition, the cytotoxicity of these compounds was measured on A549, MCF-7, and HeLa cancer cell lines. Among them, compounds 1 and 7 displayed cytotoxicity against the A549 cell line with IC50 values of 28.41 ± 0.12 µM and 39.06 ± 0.05 µM, respectively.

4.
Cancer Treat Rev ; 112: 102491, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36502615

RESUMO

Tenosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.


Assuntos
Tumor de Células Gigantes de Bainha Tendinosa , Qualidade de Vida , Humanos , Consenso , Tumor de Células Gigantes de Bainha Tendinosa/tratamento farmacológico , Tumor de Células Gigantes de Bainha Tendinosa/patologia
5.
J Ethnopharmacol ; 300: 115693, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36075272

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shi-Wei-Ru-Xiang pills (SW) as a tradition Tibetan medicine has been clinically proved effective in rheumatoid arthritis (RA) treatment. However, the underlying mechanism of SW remains unclear. AIM OF THE STUDY: This study aimed to investigate the anti-arthritic effect of SW and its possible mechanisms of action. MATERIALS AND METHODS: A CIA rat model in vivo, and IL-1ß-stimulated synoviocytes or chondrocytes and a co-culture system (IL-1ß-stimulated synoviocytes/chondrocytes) in vitro were used to evaluate the effects of SW on the treatment of RA. Arthritic score, paw swelling rate, hematoxylin-eosin (HE) staining, and Safranin-O-Fast green (S-O) staining were used to evaluate the anti-arthritic activity of SW in CIA rats. TUNEL assay or flow cytometry were performed to measure chondrocytes apoptosis in vivo and invitro. The effects of SW on the expression and production of pro-inflammatory cytokines were assessed by qRT-PCR and Elisa. The inhibitory effects of SW on the phosphorylation of p38, Erk1/2, and STAT3 were analyzed by Western blot. RESULTS: SW treatment significantly alleviated paw swelling, severity of arthritic and cartilage destruction in CIA rats. Moreover, SW decreased the expression of mRNAs of proinflammatory cytokines including TNF-α, IL-1ß and IL-6 in the synovium, suppressed the production of these pro-inflammatory cytokines in serum and hind paws, downregulated the protein expression of p-p38, p-Erk1/2 and p-STAT3, and protected the chondrocytes apoptosis in CIA rats. Consistent with the results in vivo, SW also inhibited the activation of MAPK and STAT3 pathways, suppressed the expression of pro-inflammatory cytokines in IL-1ß-stimulated synoviocytes, and attenuated chondrocytes apoptosis in IL-1ß-stimulated chondrocytes. In the co-culture system, SW pre-treatment in IL-1ß-stimulated synoviocytes exhibited inhibition of chondrocytes apoptosis, which was associated with attenuation of inflammation in synoviocytes. CONCLUSION: These results suggested that the underlying mechanisms by which SW exerts its anti-arthritis effect may be related to the reduction of proinflammatory cytokine levels, inhibition of p38, Erk1/2 and STAT3 phosphorylation, and attenuating of chondrocyte apoptosis.


Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Colágeno , Citocinas/metabolismo , Edema/tratamento farmacológico , Interleucina-6 , Ratos , Fator de Necrose Tumoral alfa
6.
Zhongguo Zhong Yao Za Zhi ; 47(19): 5383-5388, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36472046

RESUMO

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.


Assuntos
Medicina Tradicional Tibetana , Pesquisa Farmacêutica , Tibet , Controle de Qualidade , Indústria Farmacêutica
7.
Dalton Trans ; 51(40): 15507-15514, 2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36165211

RESUMO

Since nickel exhibits good binding energy and is inexpensive, it is widely applied as a hydrogen evolution reaction (HER) electrocatalyst. Among all Ni-based materials, nickel selenide (NiSe) shows a unique electronic structure as a semiconductor with good electrocatalytic activity. Herein, we prepare Co-doped NiSe (Ni1-xCoxSe) with a structure of uniform corrugations by one-step chemical vapor deposition. For comparison, Fe-doped NiSe (Ni1-xFexSe) and NiSe are also prepared using the same method. In alkaline electrolyte, Ni1-xCoxSe shows great HER performance in terms of low overpotential (93 mV@10 mA cm-2 and 140 mV@50 mA cm-2) and long-term stability. Moreover, with the assistance of solar energy, the overpotential needed for Ni1-xCoxSe is reduced, making Ni1-xCoxSe better than most reported NiSe-based HER catalysts. On the other hand, the current density of Ni1-xCoxSe is 13 mA cm-2@93 mV and 63 mA cm-2@140 mV with illumination, which is 30% and 26% higher than that without solar illumination assistance, respectively. Therefore, we believe that inducing sunlight to electrocatalytic hydrogen evolution in water splitting could be a supplementary footprint toward the utilization of solar energy.

9.
Phytomedicine ; 85: 153535, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33819766

RESUMO

BACKGROUND: Quality control exerted great importance on the clinical application of drugs for ensuring effectiveness and safety. Due to chemical complexity, diversity among different producing areas and harvest seasons, as well as unintentionally mixed with non-medicinal parts, the current quality standards of traditional Chinese medicine (TCM) still faced challenges in evaluating the overall chemical consistency. PURPOSE: We aimed to develop a new strategy to discover potential quality marker (Q-marker) of TCM by integrating plant metabolomics and network pharmacology, using Periplocae Cortex (GP, the dried root bark of Periploca sepium Bge.) as an example. METHODS: First, plant metabolomics analysis was performed by UPLC/Q-TOF MS in 89 batches of samples to discover chemical markers to distinguish medicinal parts (GP) and non-medicinal parts (the dried stem bark of Periploca sepium Bge. (JP)), harvest seasons and producing region of Periplocae Cortex. Second, network pharmacology was applied to explore the initial linkages among chemical constituents, targets and diseases. Last, potential Q-marker were selected by integrating analysis of plant metabolomics and network pharmacology, and the quantification method of Q-marker was developed by using UPLC-TQ-MS. RESULTS: The chemical profiling of GP and JP was investigated. Fifteen distinguishing features were designated as core chemical markers to distinguish GP and JP. Besides, the content of 4-methoxybenzaldehyde-2-O-ß-d-xylopyranosyl-(1→6)-ß-d-glucopyranoside could be used to identify Periplocae Cortex harvested in spring-autumn or summer. Meanwhile, a total of 15 components targeted rheumatoid arthritis were screened out based on network pharmacology. Taking absorbed constituents into consideration, 23 constituents were selected as potential Q-marker. A simultaneous quantification method (together with 11 semi-quantitative analysis) was developed and applied to the analysis of 20 batches of commercial Periplocae Cortex on the market. The PLS-DA model was successfully developed to distinguish GP and JP samples. In addition, the artificially mixed GP sample, which contained no less than 10% of the adulterant (JP), could also be correctly identified. CONCLUSION: Our results indicated that 9 ingredients could be considered as Q-marker of Periplocae Cortex. This study has also demonstrated that the plant metabolomics and network pharmacology could be used as an effective approach for discovering Q-marker of TCM to fulfill the evaluation of overall chemical consistency among samples from different producing areas, harvest seasons, and even those commercial crude drugs, which might be mixed with a small amount of non-medicinal parts.


Assuntos
Medicamentos de Ervas Chinesas/química , Metabolômica , Periploca/química , Controle de Qualidade , Animais , Biomarcadores , China , Cromatografia Líquida de Alta Pressão , Contaminação de Medicamentos , Espectrometria de Massas , Medicina Tradicional Chinesa/normas , Camundongos , Raízes de Plantas/química , Células RAW 264.7
10.
Biomed Pharmacother ; 133: 110844, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33186793

RESUMO

Cerebral palsy (CP) is a non-progressive motor-impairment disorder related to brain injury early in development. To gain new insights into the mechanisms of CP and the therapeutic efficacy of Baimai ointment, we used a high-throughput quantitative proteomic approach to evaluate proteomic changes in the hippocampus and motor cortex in a rat model of CP induced by lipopolysaccharide (LPS) combined with hypoxia/ischemia (H/I). More than 2000 proteins were identified in each brain region with high confidence. Quantitative analysis demonstrated profound disturbances in the proteomes of the hippocampus and motor cortex after LPS + H/I, in addition to the disruption of the motor system. In contrast, the topical application of Baimai ointment not only alleviated the motor deficit in the CP model rats, but also restored the proteomes in the brain cortex. Furthermore, astrocytes in the hippocampus were strongly activated in the Baimai-treated CP rat brains, associated with an increase in neurotrophic factors. Proteomic analysis demonstrated that the CP model induced neuroinflammatory responses in the brain which were reversed by the topical application of Baimai ointment. This study highlights the unexpected roles of hippocampus and motor cortex neurons in CP progress and treatment, thus providing potentially novel therapeutic targets for CP.


Assuntos
Comportamento Animal/efeitos dos fármacos , Paralisia Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Hipocampo/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Córtex Motor/efeitos dos fármacos , Proteoma , Proteômica , Administração Cutânea , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Paralisia Cerebral/metabolismo , Paralisia Cerebral/fisiopatologia , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Córtex Motor/metabolismo , Córtex Motor/fisiopatologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pomadas , Gravidez , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
11.
Clin Infect Dis ; 73(11): e3949-e3955, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-33165503

RESUMO

BACKGROUND: We evaluated an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine for immunogenicity and safety in adults aged 18-59 years. METHODS: In this randomized, double-blinded, controlled trial, healthy adults received a medium dose (MD) or a high dose (HD) of the vaccine at an interval of either 14 days or 28 days. Neutralizing antibody (NAb) and anti-S and anti-N antibodies were detected at different times, and adverse reactions were monitored for 28 days after full immunization. RESULTS: A total of 742 adults were enrolled in the immunogenicity and safety analysis. Among subjects in the 0, 14 procedure, the seroconversion rates of NAb in MD and HD groups were 89% and 96% with geometric mean titers (GMTs) of 23 and 30, respectively, at day 14 and 92% and 96% with GMTs of 19 and 21, respectively, at day 28 after immunization. Anti-S antibodies had GMTs of 1883 and 2370 in the MD group and 2295 and 2432 in the HD group. Anti-N antibodies had GMTs of 387 and 434 in the MD group and 342 and 380 in the HD group. Among subjects in the 0, 28 procedure, seroconversion rates for NAb at both doses were both 95% with GMTs of 19 at day 28 after immunization. Anti-S antibodies had GMTs of 937 and 929 for the MD and HD groups, and anti-N antibodies had GMTs of 570 and 494 for the MD and HD groups, respectively. No serious adverse events were observed during the study period. CONCLUSIONS: Adults vaccinated with inactivated SARS-CoV-2 vaccine had NAb as well as anti-S/N antibody and had a low rate of adverse reactions. CLINICAL TRIALS REGISTRATION: NCT04412538.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina
12.
Biomed Chromatogr ; 34(4): e4807, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32020626

RESUMO

Periplocae Cortex, named Xiang-Jia-Pi in China, has been widely used to treat autoimmune diseases, especially rheumatoid arthritis. However, the in vivo substances of Periplocae Cortex remain unknown yet. In this study, an ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used for profiling the chemical components and related metabolites of Periplocae Cortex. A total of 98 constituents were identified or tentatively characterized in Periplocae Cortex: 42 C21 steroidal glycosides, 10 cardiac glycosides, 23 organic acids, 4 aldehydes, 7 triterpenes, and 12 other types. Among them, 18 components were unambiguously identified by comparison with reference standards. In addition, 176 related xenobiotics (34 prototypes and 142 metabolites) were screened out and characterized in rats' biosamples (plasma, urine, bile, and feces) after the oral administration of Periplocae Cortex. Moreover, the metabolic fate of periplocoside S-4a, a C21 steroidal glycoside, was proposed for the first time. In summary, phase II reactions (methylation, glucuronidation, and sulfation), phase I reactions (hydrolysis reactions, oxygenation, and reduction), and their combinations were the predominant metabolic reactions of Periplocae Cortex in rat. It is the first report to reveal the in vivo substances and metabolism feature of Periplocae Cortex. This study also provided meaningful information for further pharmacodynamics study of Periplocae Cortex, as well as its quality control research.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/metabolismo , Espectrometria de Massas/métodos , Periploca/química , Administração Oral , Aldeídos/análise , Aldeídos/química , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Glicosídeos/análise , Glicosídeos/química , Masculino , Casca de Planta/química , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley , Triterpenos/análise , Triterpenos/química
13.
Front Pharmacol ; 10: 354, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31024317

RESUMO

The pathogenesis of itchy skin diseases including allergic contact dermatitis (ACD) is complicated and the treatment of chronic itch is a worldwide problem. One traditional Tibetan medicine, Qingpeng ointment (QP), has been used in treatment of ACD in China for years. In this study we used HPLC and LC/MS analysis, combined with a BATMAN-TCM platform, for detailed HPLC fingerprint analysis and network pharmacology of QP, and investigated the anti-inflammatory and antipruritic activities of QP on ACD induced by squaric acid dibutylester (SADBE) in mice. The BATMAN-TCM analysis provided information of effector molecules of the main ingredients of QP, and possible chronic dermatitis-associated molecules and cell signaling pathways by QP. In ACD mice, QP treatment suppressed the scratching behavior induced by SADBE in a dose-dependent manner and inhibited the production of Th1/2 cytokines in serum and spleen. Also, QP treatment reversed the upregulation of mRNAs levels of itch-related genes in the skin (TRPV4, TSLP, GRP, and MrgprA3) and DRGs (TRPV1, TRPA1, GRP, and MrgprA3). Furthermore, QP suppressed the phosphorylation of Erk and p38 in the skin. In all, our work indicated that QP can significantly attenuate the pathological alterations of Th1/2 cytokines and itch-related mediators, and inhibit the phosphorylation of MAPKs to treat the chronic itch.

14.
Hu Li Za Zhi ; 65(3): 88-95, 2018 06.
Artigo em Chinês | MEDLINE | ID: mdl-29790143

RESUMO

Immune checkpoint inhibitors (ICIs) have become the new posterchild of cancer treatment in recent years largely due to their impressive clinical efficacy. Drugs targeting cytotoxic T- lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1) antibodies, e.g., ipilimumab (Yervoy®), pembrolizumab (Keytruda®), and nivolumab (Opdivo®), reinvigorate cytotoxic T cells to kill cancer cells in patients. Despite the impressive clinical benefits, ICIs may induce immune-related adverse events (irAE) of the skin, gastrointestinal tract, liver, endocrine, and lung with a wide spectrum of severity. Rare but severe irAEs of critical organs such as the heart and central nervous system have also been reported. Clinical practitioners must recognize the early signs and symptoms of irAE as well as related management strategies.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antígeno CTLA-4/antagonistas & inibidores , Ipilimumab/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Humanos , Nivolumabe
15.
Nanoscale Res Lett ; 12(1): 405, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28610398

RESUMO

SnO2 nanobelts (NBs) have unique structural and functional properties which attract great attention in gas detecting. In this work, Eu doping is adopted to improve the gas sensitivity of pure SnO2, especially to enhance the response to one single gas. The Eu-doped SnO2 NBs, pure-SnO2 NBs, and their single NB devices are fabricated by simple techniques. The sensing properties of the two sensors have been experimentally investigated. It is found that the two sensors possess long-term stability with rapid response performance, and Eu doping improves the electronic performance and the gas-sensing response, particularly to acetone. In addition, the effects aroused by Eu have been theoretically calculated, which indicates that Eu doping enhances the sensing performance of SnO2. Consequently, Eu-doped SnO2 NBs show great potential applications in the detection of acetone.

16.
Hu Li Za Zhi ; 63(5): 121-126, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-27699747

RESUMO

Human epidermal growth factor receptor (HER2)-positive breast cancer is associated with a more aggressive disease and poor prognosis. The development of trastuzumab, a HER2-targeted agent, has changed the paradigm of HER2-positive breast cancer treatment and improved survival rates dramatically. However, metastatic HER2-positive breast cancer patients eventually develop resistance to this treatment regimen eventually. A new anti-HER2 antibody-drug conjugate, Trastuzumab emtansine (T-DM1), has been shown to improve treatment efficacy. However, side effects that differ from trastuzumab, including thrombocytopenia, liver dysfunction, fatigue, cardiotoxicity, pneumonitis, and peripheral neuropathy, may occur. Clinical nurses must understand the mechanism of this new agent and be aware of the symptoms and signs related to its side effects. Furthermore, clinical nurses should understand the varying degrees of these side effects, their probable causes, and the potential approaches to their management. Finally, clinical nurses must understand how to administer this agent in order to ensure patient safety. Understanding the side effects of T-DM1 and their management will help elevate nursing quality and caring efficacy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Maitansina/análogos & derivados , Receptor ErbB-2/análise , Ado-Trastuzumab Emtansina , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias da Mama/patologia , Feminino , Humanos , Maitansina/administração & dosagem , Maitansina/efeitos adversos , Maitansina/uso terapêutico , Metástase Neoplásica , Trastuzumab
17.
BMC Cancer ; 16: 466, 2016 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-27412562

RESUMO

BACKGROUND: To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. METHODS: Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2-4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. RESULTS: Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were -12.8 and -24.7 % for Peak, -46.6 and -65.8 % for Slope, -27.9 and -55.5 % for iAUC 60 , and -46.6 and -63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. CONCLUSION: Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01281696 , registered prospectively on December 24, 2010.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Encefálicas/irrigação sanguínea , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/secundário , Neoplasias da Mama/tratamento farmacológico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Meios de Contraste/administração & dosagem , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento
18.
Clin Nucl Med ; 41(9): 708-9, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27405028

RESUMO

Osteosarcomas are aggressive with a high incidence of recurrence and metastasis. Cardiac osteosarcoma metastasis is rare. We described a 17-year-old boy who had right distal femoral osteosarcoma with lung metastases. During follow-up, right ventricular (RV) metastasis was noted and confirmed by histopathological examination of the surgical specimen. F-NaF PET/CT was then arranged 1 month after debulking surgery for residual tumor survey. The images showed intense F-NaF uptake at RV region, suggestive of residual cardiac metastases.


Assuntos
Fluordesoxiglucose F18/farmacocinética , Neoplasias Cardíacas/diagnóstico por imagem , Neoplasia Residual/diagnóstico por imagem , Osteossarcoma/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/farmacocinética , Adolescente , Neoplasias Ósseas/patologia , Neoplasias Cardíacas/secundário , Humanos , Masculino , Imagem Multimodal/métodos , Osteossarcoma/patologia
19.
Sci Rep ; 5: 17879, 2015 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-26671300

RESUMO

IHC4 and PAM50 assays have been shown to provide additional prognostic information for patients with early breast cancer. We evaluated whether incorporating TP53 mutation analysis can further enhance their prognostic accuracy. We examined TP53 mutation and the IHC4 score in tumors of 605 patients diagnosed with stage I-III breast cancer at National Taiwan University Hospital (the NTUH cohort). We obtained information regarding TP53 mutation and PAM50 subtypes in 699 tumors from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort. We found that TP53 mutation was significantly associated with high-risk IHC4 group and with luminal B, HER2-enriched, and basal-like subtypes. Despite the strong associations, TP53 mutation independently predicted shorter relapse-free survival (hazard ratio [HR] = 1.63, P = 0.007) in the NTUH cohort and shorter breast cancer-specific survival (HR = 2.35, P = <0.001) in the METABRIC cohort. TP53 mutational analysis added significant prognostic information in addition to the IHC4 score (∆ LR-χ(2) = 8.61, P = 0.002) in the NTUH cohort and the PAM50 subtypes (∆ LR-χ(2) = 18.9, P = <0.001) in the METABRIC cohort. We conclude that incorporating TP53 mutation analysis can enhance the prognostic accuracy of the IHC4 and PAM50 assays.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Mutação , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Taiwan , Proteína Supressora de Tumor p53/metabolismo , Adulto Jovem
20.
Sensors (Basel) ; 15(12): 29950-7, 2015 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-26633404

RESUMO

Eu-doped In2O3 nanobelts (Eu-In2O3 NBs) and pure In2O3 nanobelts (In2O3 NBs) are synthesized by the carbon thermal reduction method. Single nanobelt sensors are fabricated via an ion beam deposition system with a mesh-grid mask. The gas-sensing response properties of the Eu-In2O3 NB device and its undoped counterpart are investigated with several kinds of gases (including H2S, CO, NO2, HCHO, and C2H5OH) at different concentrations and different temperatures. It is found that the response of the Eu-In2O3 NB device to 100 ppm of H2S is the best among these gases and the sensitivity reaches 5.74, which is five times that of pure In2O3 NB at 260 °C. We also found that the former has an excellent sensitive response and great selectivity to H2S compared to the latter. Besides, there is a linear relationship between the response and H2S concentration when its concentration changes from 5 to 100 ppm and from 100 to 1000 ppm. The response/recovery time is quite short and remains stable with an increase of H2S concentration. These results mean that the doping of Eu can improve the gas-sensing performance of In2O3 NB effectually.

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