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BACKGROUND: Lucitanib is a novel multi-target inhibitor of FGFR1-3, VEGFR 1-3, and PDGFR α/ß. Here, we evaluated the safety, tolerability, and preliminary efficacy of lucitanib in recurrent and metastatic nasopharyngeal carcinoma (RM-NPC). METHODS: Patients with pretreated RM-NPC were randomly divided into two treatment arms: continuous or intermittent treatment. The primary endpoint was safety and tolerability. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). RESULTS: One hundred percent of patients in the continuous arm and 90% of patients in the intermittent arm had at least one treatment-related AE (TRAE). Grade ≥3 related TRAEs occurred in 5 patients in the continuous arm (5/10, 50%). No TRAEs grade >3 occurred in the intermittent arm. The ORR and DCR of the continuous arm was 20% and 90%, and the intermittent arm was 10% and 60%, respectively. All responses were observed by the first evaluation. The duration of response was more than 1 year, with two patients still on treatment with sustained response at more than 3 years. CONCLUSION: Lucitanib has promising clinical activity and tolerable safety profile in heavily pretreated patients with NPC. Patients who responded to lucitanib treatment generally achieved a long DoR. Lucitanib is now being evaluated in phase II/III studies. CLINICALTRIALS.GOV IDENTIFIER: NCT03260179.
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Neoplasias Nasofaríngeas , Quinolinas , Humanos , Naftalenos , Carcinoma Nasofaríngeo/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Quinolinas/uso terapêuticoRESUMO
Chinese quince seed (CQS) is an underutilized oil source and a potential source of unsaturated fatty acids and α-tocopherol-rich oil. Subcritical fluid (SCF) extraction is executed at lower pressures and temperatures than the pressures and temperatures used in supercritical fluid extraction. However, no studies on the SCF extraction of CQS oil are reported. Therefore, the objective of this study was to evaluate the use of SCF for the extraction of CQS oil and to compare the use of SCF with the classical Soxhlet (CS) and supercritical CO2 (SC-CO2) extraction methods. Response surface methodology (RSM) was used to investigate the extraction conditions: temperature (45-65 °C), time (30-50 min), and solvent/solid ratio (5-15 mL/g). The optimization results showed that the highest yield (27.78%) was obtained at 56.18 °C, 40.20 min, and 12.57 mL/g. The oil extracted by SCF had a higher unsaturated fatty acid content (86.37%-86.75%), higher α-tocopherol content (576.0-847.6 mg/kg), lower acid value (3.97 mg/g), and lower peroxide value (0.02 meq O2/kg) than extractions using CS and SC-CO2 methods. The SCF-defatted meal of oilseed exhibited the highest nitrogen solubility index (49.64%) and protein dispersibility index (50.80%), demonstrating that SCF extraction was a promising and efficient technique as an alternative to CS and SC-CO2 methods, as very mild operating conditions and an eco-friendly solvent can be used in the process with maximum preservation of the quality of the meal.
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Óleos de Plantas/química , Rosaceae/química , Sementes/química , Pressão Atmosférica , Ácidos Graxos Insaturados/análise , Temperatura , alfa-Tocoferol/análiseRESUMO
INTRODUCTION: An increasing number of targeted drugs have been tested for the treatment of nasopharyngeal carcinoma (NPC). However, targeted therapy-related oncogenic mutations have not been fully evaluated. This study aimed to detect targeted therapy-related oncogenic mutations in NPC and to determine which targeted therapy might be potentially effective in treating NPC. METHODS: By using the SNaPshot assay, a rapid detection method, 19 mutation hotspots in 6 targeted therapy-related oncogenes were examined in 70 NPC patients. The associations between oncogenic mutations and clinicopathologic factors were analyzed. RESULTS: Among 70 patients, 12 (17.1%) had mutations in 5 oncogenes: 7 (10.0%) had v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) mutation, 2 (2.8%) had epidermal growth factor receptor (EGFR) mutation, 1 (1.4%) had phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutation, 1 (1.4%) had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation, and 1 (1.4%) had simultaneous EGFR and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations. No significant differences were observed between oncogenic mutations and clinicopathologic characteristics. Additionally, these oncogenic mutations were not associated with tumor recurrence and metastasis. CONCLUSIONS: Oncogenic mutations are present in NPC patients. The efficacy of targeted drugs on patients with the related oncogenic mutations requires further validation.
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Mutação , Neoplasias Nasofaríngeas , Oncogenes , Farmacogenética , Carcinoma , Classe I de Fosfatidilinositol 3-Quinases , Receptores ErbB , Humanos , Carcinoma Nasofaríngeo , Recidiva Local de Neoplasia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas B-rafRESUMO
AIM: To confirm whether the aflibercept dose, plus docetaxel, in western study TCD6120 is appropriate for Chinese patients with nasopharyngeal carcinoma (NPC) and other solid tumors. MATERIALS & METHODS: To assess dose-limiting toxicity of every 3-week 4 mg/kg or 6 mg/kg aflibercept plus 75 mg/m(2) docetaxel. RESULTS: Previously treated patients (16 with NPC and 4 with lung cancer) were enrolled. At 6 mg/kg aflibercept: one dose-limiting toxicity was seen (neutropenic infection); the most frequently reported all-grade adverse events were oropharyngeal pain, stomatitis and alopecia; the most frequently reported grade 3/4 adverse events were oropharyngeal pain, stomatitis and neutropenic infection. Eleven patients had partial response and 3 had stable disease. CONCLUSION: Preliminary efficacy data for docetaxel/aflibercept are encouraging in Chinese patients with NPC. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry ( ClinicalTrials.gov , NCT01148615).
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Taxoides/administração & dosagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Povo Asiático , Carcinoma , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Metástase Neoplásica , Radiografia , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Taxoides/efeitos adversos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
To improve cancer pain management, the Medical Oncology Department of Sun Yat-sen University Cancer Center (SYSUCC) launched the Good Pain Management (GPM) Ward Program, which has been recognized by the Chinese Ministry of Health and promoted throughout the nation. This retrospective case-control study was designed to evaluate the effectiveness of the program. Patients diagnosed with malignant solid tumors with bone metastasis were eligible. Patients who were admitted 6 months before the initiation of the GPM program were used as the control group, and patients admitted 6 months after the initiation of the program were used as the GPM group. The pain-reporting rate and pain management index (PMI) were calculated. The pain levels before and after pain management were compared. A total of 475 patients (244 in the control group and 231 in the GPM group) were analyzed. The pain-reporting rate of the GPM group was significantly higher than that of the control group (62.8% vs. 37.7%, P < 0.001). The PMI of the GPM group was significantly higher than that of the control group (0.083 vs. -0.261, P < 0.001). Therefore, the GPM Ward Program improved the pain management of cancer patients and provided experience for improving cancer pain management in the future.
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Neoplasias Ósseas , Manejo da Dor/métodos , Idoso , Estudos de Casos e Controles , China , Humanos , Oncologia , Neoplasias , Dor , Medição da Dor , Estudos RetrospectivosRESUMO
Both platinum-based doublet chemotherapy (PBC) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) prolong the survival of patients with advanced non-small cell lung cancer (NSCLC). In early studies, most patients underwent PBC as first-line treatment, but not all patients could afford EGFR-TKIs as second-line treatment. To understand the impact of PBC and EGFR-TKIs on NSCLC prognosis, we evaluated the association between the receipt of both regimens and overall survival (OS). Using MEDLINE and EMBASE, we identified prospective, randomized, controlled phase III clinical trials in advanced NSCLC that met the inclusion criteria: in general population with advanced NSCLC, the percentage of patients treated with both PBC and EGFR-TKIs was available in the trial and OS was reported. After collecting data from the selected trials, we correlated the percentage of patients treated with both PBC and EGFR-TKIs with the reported OS, using a weighted analysis. Fifteen phase III clinical trials--involving 11,456 adult patients in 32 arms--were included in the analysis, including 6 trials in Asian populations and 9 in non-Asian (predominantly Caucasian) populations. The OS was positively correlated with the percentage of patients treated with both PBC and EGFR-TKIs (r = 0.797, P < 0.001). The correlation was obvious in the trials in Asian populations (r = 0.936, P < 0.001) but was not statistically significant in the trials in predominantly Caucasian populations (r = 0.116, P = 0.588). These results suggest that treatment with PBC and EGFR-TKIs may provide a survival benefit to patients with advanced NSCLC, highlighting the importance of having both modalities available for therapy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Ensaios Clínicos Fase III como Assunto , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Platina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de SobrevidaRESUMO
Tigernut has been recognized as a promising resource for edible oil and starch. However, the research on the quality characteristics of tigernut from different regions is lagging behind, which limits the application of tigernut in food industry. Tigernut tubers were obtained from six major growing regions in China, and the physicochemical properties of their main components, oil and starch, were characterized. Tigernut tubers from Baoshan contained the most oil (30.12%), which contained the most ß-carotene (130.4 µg/100 g oil) due to high average annual temperature. Gas chromatography analysis and fingerprint analysis results indicated that tigernut oil (TNO) consists of seven fatty acids, of which oleic acid is the major component. Changchun TNO contained the least total tocopherols (6.04 mg/100 g oil) due to low average annual temperature. Tigernut tubers from Chifeng (CF) contained the most starch (34.85%) due to the large diurnal temperature range. Xingtai starch contained the most amylose (28.4%). Shijiazhuang starch showed the highest crystallinity (19.5%). Anyang starch had the highest pasting temperature (76.0°C). CF starch demonstrated superior freeze-thaw stability (syneresis: 50%) due to low mean annual precipitation. The results could be further applied to support tigernut industries and relevant researchers that looks for geographical origin discrimination and improvements on tigernut quality, with unique physicochemical and technological properties.
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Cyperus , Amido , Amido/química , Cyperus/química , Óleos de Plantas/química , Verduras , ChinaRESUMO
This study was to explore the internal reasons for the changes in oil absorption performance of tigernut starch (TS) by revealing the high-temperature induced variations of structural and functional properties of TS. The results showed that as the temperature increased from 80 °C to 140 °C, the degree of starch gelatinization increased, while the proportion of double helix structures, the total proportion of B1 and B2 chains, the relative crystallinity and the molecular weight decreased, accompanied by the fragmentation and swelling of TS granules. The oxidation of tigernut oil (TNO) led to a decrease in oil density and an increase in total polar component content. These phenomena could result in an increase of oil absorption capacity of TS and starch-lipid complex index. With further increase in temperature from 170 °C to 200 °C, the disruption of the crystalline structure and chain structure increased, resulting in the melting and disintegration of TS granules. This caused a decrease in the starch-oil contact area and capillary absorption of TNO by the TS granules. The results will contribute to revealing the effect of high-temperature induced changes in the structural and functional properties of TS on its oil absorption properties.
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Pain is the cardinal symptom of many debilitating diseases and results in heavy health and economic burdens worldwide. Asarum (Asarum sieboldii Miq.) is a commonly used analgesic in Chinese medicine. However, the analgesic components and mechanisms of asarum in acute and chronic pain mice model remain unknown. In this study, we first generated asarum water extract and confirmed strong analgesic properties in mice in both the acute thermal and mechanical pain models, as well as in the complete Freund's adjuvant (CFA) induced chronic inflammatory pain model. Second, we identified higenamine as a major component of asarum and found that higenamine significantly inhibited thermal and mechanical induced acute pain and CFA induced chronic inflammatory pain. Then, using Trpv4-/- mice, we found that TRPV4 is necessary for CFA induced thermal and mechanical allodynia, and demonstrated that higenamine analgesia in the CFA model is partly through TRPV4 channel inhibition. Finally, we found that GSK1016790A, a TRPV4 agonist, induced calcium response was significantly inhibited by higenamine in both cultured DRG neurons and TRPV4 transfected HEK293 cells. Consistent with calcium imaging results, higenamine pretreatment also dose-dependently inhibited GSK1016790A induced acute pain. Taken together, our behavior and calcium imaging results demonstrate that the asarum component higenamine inhibits acute and chronic inflammatory pain by modulation of TRPV4 channels.
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Alcaloides , Dor Crônica , Canais de Cátion TRPV , Tetra-Hidroisoquinolinas , Animais , Humanos , Camundongos , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Cálcio/metabolismo , Dor Crônica/tratamento farmacológico , Células HEK293 , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Leucina/análogos & derivados , Sulfonamidas/farmacologia , Canais de Cátion TRPV/antagonistas & inibidoresRESUMO
Heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) are hazardous substances produced when food is heated. In this study, the ability of plasma-activated water (PAW) to simultaneously mitigate production of HAAs and AGEs in roasted beef patties was investigated. Assays of free radicals, lipid peroxidation, and active carbonyls were used to analyze the mechanisms. PAW treatment decreased the contents of free HAAs, free AGEs, bound HAAs, and bound AGEs to 12.65 ng/g, 0.10 µg/g, 297.74 ng/g, and 4.32 µg/g, with the inhibition rates of 23.88%, 23.08%, 11.02%, and 8.47%, respectively. PAW treatment decreased HAAs and AGEs and mitigated their increase during storage. The decrease of HAAs and AGEs in PAW-treated samples was correlated with the enhancement of antioxidant capacity. The increase of free radical scavenging ability by PAW treatment led to the decrease of lipid peroxidation and the decrease of active carbonyls, HAAs, and AGEs in meat products.
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Aminas , Produtos Finais de Glicação Avançada , Produtos da Carne , Produtos Finais de Glicação Avançada/metabolismo , Animais , Bovinos , Produtos da Carne/análise , Aminas/metabolismo , Água/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Temperatura Alta , Compostos Heterocíclicos/farmacologia , Compostos Heterocíclicos/química , Culinária , Antioxidantes/metabolismo , Antioxidantes/química , Antioxidantes/farmacologiaRESUMO
The abilities of Chinese quince free proanthocyanidins (FP) and bound proanthocyanidins (BP) at different levels (0.1%, 0.15%, and 0.3%) to mitigate heterocyclic aromatic amine (HAA) formation in fried chicken patties were investigated for the first time and compared with vitamin C (Vc). FP and BP reduced HAAs in a dose-dependent manner. Significantly, high concentrations of FP (0.3%) resulted in a reduction of PhIP, harman, and norharman levels by 59.84%, 22.91%, and 38.21%, respectively, in chicken patties. The addition of proanthocyanidins significantly (p < 0.05) reduced the weight loss of fried chicken patties. Furthermore, a positive correlation was observed among pH, weight loss, and total HAA formation in all three groups (FP, BP, and Vc). Multivariate analysis showed that FP had a more pronounced effect than BP from the perspective of enhancing the quality of fried chicken patties and reducing the formation of HAAs. These results indicate that proanthocyanidins, both BP and FP, but especially FP, from Chinese quince can inhibit the formation of carcinogenic HAAs when added to protein-rich foods that are subsequently fried.
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Aminas , Galinhas , Culinária , Proantocianidinas , Proantocianidinas/análise , Proantocianidinas/farmacologia , Animais , Aminas/química , Culinária/métodos , Compostos Heterocíclicos/química , Rosaceae/química , População do Leste AsiáticoRESUMO
Surface modification of nanostructured lipid carriers (NLCs) can be an effective way to improve their oral delivery for active ingredients. In this study, four type of guar gum series modified NLCs for the delivery of phytosterols (PS) were constructed and the effects of the polysaccharides on their structure and physicochemical properties were studied. DLS and AFM results revealed that positively charged polysaccharides could bind to PS-NLCs through electrostatic attraction and made the complexes finally take positive charges, while negatively charged polysaccharides were more likely to fill in the gaps of NLC systems to achieve a balance between electrostatic repulsion and intermolecular forces. Although all four polysaccharides exhibited good storage stability and controlled release of PS in simulated intestinal digestion, PS-NLCs modified with partially hydrolyzed cationic guar gum (PHCG) at medium or high concentrations exhibited better gastric stability, mucoadhesion, and cellular uptake, which had considerable significance for improving the oral bioavailability of PS. This might be related to the coating structure of PHCG-PS-NLCs confirmed by AFM, FTIR, and Raman characterization. This study provide a reference value for designing suitable PS-NLC complexes without synthetic surfactants.
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Nanoestruturas , Fitosteróis , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Lipídeos/química , Eletricidade Estática , Galactanos , Nanoestruturas/química , Tamanho da Partícula , Administração OralRESUMO
Asarinin, an isomer of sesamin, has attracted attention because it has stronger biological properties than sesamin. The research on the conversion of sesamin into asarinin is limited. In this study, solid acid catalysts were screened and applied to promote the conversion of sesamin into asarinin in sesame oil. The results showed that citric acid loaded on zeolite beta (CTAH) was the optimal catalyst for asarinin production among the prepared catalysts. Characterization showed that CTAH had the greatest pore volume, largest surface area and strongest acid content. Response surface methodology (RSM) was applied to optimize the reaction conditions for asarinin yield using CTAH. The optimal reaction conditions were as follows: temperature, 85 °C; time, 2.7 h; catalyst amount, 1.6%. The predicted and experimental values of asarinin yield were 50.79 and 51.80 mg/100 g, respectively. The peroxide value and color in sesame oil samples treated with CTAH were clearly improved. In short, CTAH is a solid acid catalyst with potential application in the industrial conversion of sesamin into asarinin and in the improvement of sesame oil.
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Over the years, concentrated efforts have been directed toward the improvement of desirable characteristics and attributes in peanut cultivars. Most of these breed improvement programs have been targeting attributes that involve peanut growth, productivity, drought and disease tolerance, and oil quality and content, with only a few articles focusing directly on improvements in peanut butter organoleptic qualities. There are numerous peanut cultivars on the market today, with widely differing chemical compositions and metabolite profiles, about which little is known concerning their suitability for making peanut butter. In this review, we detail how the numerous peanut varieties on the market today, with their genetically conferred physiochemical attributes, can significantly affect the sensory quality attributes of peanut butter, even in peanut butter processing lines with optimized processes. If other peanut butter processing parameters are held constant, variations in the chemical composition and metabolite profiles of peanuts have a significant impact on peanut butter color, flavor, texture, storage stability, shelf life, and overall product acceptance by consumers. Further research on breeding programs for peanut varieties that are specifically tailored for peanut butter production, and even more comprehensive research on the synergetic relationship between peanut chemical composition and peanut butter organoleptic quality, are still required.
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Peanut butter has a very large and continuously increasing global market. The food safety risks associated with its consumption are also likely to have impacts on a correspondingly large global population. In terms of prevalence and potential magnitude of impact, contamination by Salmonella spp., and aflatoxins, are the major food safety risks associated with peanut butter consumption. The inherent nature of the Salmonella spp., coupled with the unique chemical composition and structure of peanut butter, present serious technical challenges when inactivating Salmonella spp. in contaminated peanut butter. Thermal treatment, microwave, radiofrequency, irradiation, and high-pressure processing all are of limited efficacy in inactivating Salmonella spp. in contaminated peanut butter. The removal of aflatoxins in contaminated peanut butter is equally problematic and for all practical purposes almost impossible at the moment. Adopting good manufacturing hygiene practices from farm to table and avoiding the processing of contaminated peanuts are probably some of the few practically viable strategies for minimising these peanut butter food safety risks. The purpose of this review is to highlight the nature of food safety risks associated with peanut butter and to discuss the effectiveness of the initiatives that are aimed at minimising these risks.
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In the present work, effects of reaction temperature, reactant concentration, catalyst loading, and rotation speed on the kinetics of sesamin conversion in a sesame oil system were studied by using citric acid loading on Hß zeolite (CA/Hß) as a catalyst. A kinetic model was built for sesamin conversion. The kinetic model fits correctly the experimental concentration of sesamin and asarinin ( R S ⢠e ⢠s ⢠a ⢠m ⢠i ⢠n 2 = 0.93 and R A ⢠s ⢠a ⢠r ⢠i ⢠n ⢠i ⢠n 2 = 0.97). The sesamin conversion is an endothermic reaction (â³H rIso = 3 4.578kJ/mol). The CA/Hß catalyst could be easily regenerated by calcination, and there was no obvious loss of catalytic activity when reused. Knowledge of the sesamin conversion is of great significance for guiding production and improving the value and nutrition of sesame oil. In a word, this study lays the foundation for the scale-up of the production of asarinin from sesame oil using CA/Hß as the catalyst.
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Background: CT053PTSA is a novel tyrosine kinase inhibitor that targets MET, AXL, VEGFR2, FLT3 and MERTK. Here, we present preclinical data about CT053PTSA, and we conducted the first-in-human (FIH) study to evaluate the use of CT053PTSA in adult patients with pretreated advanced solid tumors. Methods: The selectivity and antitumor activity of CT053PTSA were assessed in cell lines in vitro through kinase and cellular screening panels and in cell line-derived tumor xenograft (CDX) and patient-derived xenograft (PDX) models in vivo. The FIH, phase I, single-center, single-arm, dose escalation (3 + 3 design) study was conducted, patients received at least one dose of CT053PTSA (15 mg QD, 30 mg QD, 60 mg QD, 100 mg QD, and 150 mg QD). The primary objectives were to assess safety and tolerability, to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended dose of CT053PTSA for further study. Secondary objectives included pharmacokinetics, antitumor activity. Results: CT053 (free-base form of CT053PTSA) inhibited MET, AXL, VEGFR2, FLT3 and MERTK phosphorylation and suppressed tumor cell angiogenesis by blocking VEGF and HGF, respectively, in vitro. Moreover, cell lines with high MET expression exhibited strong sensitivity to CT053, and CT053 blocked the MET and AXL signaling pathways. In an in vivo study, CT053 significantly inhibited tumor growth in CDX and PDX models. Twenty eligible patients were enrolled in the FIH phase I trial. The most common treatment-related adverse events were transaminase elevation (65%), leukopenia (45%) and neutropenia (35%). DLTs occurred in 3 patients, 1/6 in the 100 mg group and 2/4 in the 150 mg group, so the MTD was set to 100 mg. CT053PTSA was rapidly absorbed after the oral administration of a single dose, and the Cmax and AUC increased proportionally as the dose increased. A total of 17 patients in this trial underwent tumor imaging evaluation, and 29.4% had stable disease. Conclusions: CT053PTSA has potent antitumor and antiangiogenic activity in preclinical models. In this FIH phase I trial, CT053PTSA was well tolerated and had a satisfactory safety profile. Further trials evaluating the clinical activity of CT053PTSA are ongoing.
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Neoplasias , Inibidores de Proteínas Quinases , Adulto , Humanos , c-Mer Tirosina Quinase , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias/patologia , Dose Máxima Tolerável , Administração OralRESUMO
OBJECTIVE: The objective of this study was to compare the effects of Sanyinjiao (SP6), Xuanzhong (GB39), and an adjacent non-meridian point on menstrual pain and uterine arterial blood flow in primary dysmenorrhea patients. DESIGN: The design of the study was a prospective, randomized controlled trial. SETTING: The setting of the study was the Shandong Institute of Medical Imaging, Jinan, China. PATIENTS: The patients were 52 women with primary dysmenorrhea. INTERVENTIONS: Women received electroacupuncture (EA) at SP6 (n=13), GB39 (n=14), and an adjacent non-meridian point (n=12), respectively, for 10 minutes when scored ≥40 on a 100-mm visual analog scale (VAS), and for 30 minutes on the next 2 days. There was no EA in the waiting list group (n=13). OUTCOME MEASURES: Primary outcomes were menstrual pain, resistance index (RI), and the ratio between peak systolic to end-diastolic flow velocity (S/D) in uterine arteries. Secondary outcomes included verbal rating scale (VRS) and retrospective symptom scale (RSS). RESULTS: The SP6 group had a highly significant reduction in VAS scores compared with the waiting list group (-23.19mm, 95% confidence interval [CI]-32.06 to -14.33, P<0.0001), GB39 group (-18.58mm, 95% CI -27.29 to -9.88, P<0.0001) and the non-meridian point group (-20.78mm, 95% CI -29.82 to -11.73, P<0.0001), respectively. A significant reduction in VRS scores was found in the SP6 group compared with the GB39 group (P=0.034) and the non-meridian point group (P=0.038). There were no significant differences of RI, S/D-values and RSS scores among the four groups (P>0.05). CONCLUSIONS: EA at SP6 can immediately relieve menstrual pain and minimize the influence of pain on daily life compared with GB39 and an adjacent non-meridian point. The data preliminarily show the specificity of SP6 for the immediate pain relief of primary dysmenorrhea.
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Pontos de Acupuntura , Dismenorreia/terapia , Eletroacupuntura , Artéria Uterina/fisiologia , Útero/irrigação sanguínea , Adolescente , Adulto , Método Duplo-Cego , Dismenorreia/fisiopatologia , Eletroacupuntura/efeitos adversos , Feminino , Humanos , Medição da Dor , Estudos Prospectivos , Fluxo Sanguíneo Regional/fisiologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To compare the value of ultrasound and magnetic resonance imaging (MRI) in detecting fetal spine and spinal cord dysplasia. METHODS: Thirty women with complicated pregnancies, age from 22 to 41 years, gestation from 23-38 weeks, were studied with MRI within 72 hours after ultrasound studies and revealed 19 cases of fetal spine with irregular, 7 cases of vertebral canal widened partly and 4 cases of anomalies of spinal curvature. Autopsy or imaging was conducted when pregnancy was terminated. A close follow-up was given for cases continuing pregnancy within 12 months after delivery. RESULTS: (1) Nineteen cases of fetal spine with irregular in ultrasound, the coincidence of antenatal sonographic diagnosis was 42% (8/19), the coincidence of antenatal MRI diagnosis was 89% (17/19). Seven cases of vertebral canal widened partly in ultrasound, the coincidence of antenatal sonographic diagnosis was 0, the coincidence of antenatal MRI diagnosis was 7/7. Four cases of anomalies of spinal curvature in ultrasound, the coincidence of antenatal sonographic diagnosis was 2/4, the coincidence of antenatal MRI diagnosis was 3/4.(2) By MRI study, one cases were conformed their ultrasound diagnosis, eleven cases were completed their ultrasound diagnosis, nine cases were made the same diagnosis as ultrasound and six cases were corrected diagnosis. By MRI and ultrasound study one case of hemivertebra, one case of butterfly vertebra and one case of dorsal dermal sinus were missed diagnosis. Ultrasound had limits and low specificity especially in fetal spinal cord. CONCLUSIONS: MRI can show the spinal cord and its lesion intuitively and has advantages in displaying fetal anomaly of spine and spinal cord. MRI is a valuable complement to sonography in difficult cases and diagnostic accuracy can be significantly improved.
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Imageamento por Ressonância Magnética , Defeitos do Tubo Neural/diagnóstico , Medula Espinal/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Feminino , Feto/anormalidades , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal/métodos , Medula Espinal/anormalidades , Coluna Vertebral/anormalidadesRESUMO
The beta-carbolines norharman and harman, two heterocyclic aromatic amines with potential mutagenicity, have been determined in vegetable oils. Identification and analysis were carried out by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry (UPLC-MS/MS). In 88 samples analysed, the concentrations of norharman and harman were < LOD to 336.22 ng/g and < LOD to 505.14 ng/g, respectively. A high variability of norharman and harman levels among different oil types was observed. Sesame-, flaxseed-, sunflower seed-, peanut- and rapeseed oils were most contaminated. Both ß-carbolines were most likely formed during roasting of the oilseeds. Oil consumption, especially of oils obtained after roasting of the seeds, was a major dietary source of the ß-carbolines norharman and harman. Under existing oil risk factors, this investigation contributes to the unprecedented and essential information for dietary assessments associated with oil consumption.