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1.
Yi Chuan ; 42(1): 73-86, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31956098

RESUMO

Chromatin architecture involves the patterns of chromatin coiling and packing as well as the mutual relative allocations of different chromatins. Besides the canonical microscopic observations, the chromatin architectural capture techniques, including the Hi-C and ChIA-PET, have been widely applied in characterization of chromatin architecture in various plant and animal model species, in which chromatin architectural features, such as the chromosome territory, compartment A/B, topological associated domains (TADs) and chromatin loops, were defined. As for the studies in plant species, replying on the two techniques above (with differences in experimental techniques and data structures), scientists have compared the variation of specific chromatin architecture features across species and/or in different cell types of the same plant species, besides detailed analyses in each individual model. Here, we mainly review the recent progresses in studies of plant chromatin architectures, in which their composition, establishing mechanism and effective factors were described and discussed. We also propose the main technical bottlenecks, describe the breaking-through progresses, and anticipate future research directions, which may offer more theoretical references for related researches in the field.


Assuntos
Montagem e Desmontagem da Cromatina , Cromatina/química , Plantas
2.
Sci Total Environ ; 703: 135532, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31759718

RESUMO

This study evaluated the effects of nano zero-valent iron (NZVI, 50 nm) on anaerobic digestion of high solids sludge (10 ± 0.5%). Compared to the blank group without NZVI, the group with NZVI at all levels (10, 20 and 30 mM) played a driving role in methane production. The maximal methane production was increased by 37.5% in the group of 30 mM NZVI. The dynamic changes of hydrogen content and VFAs showed that rapid hydrogen evolutional corrosion of NZVI made lower hydrogen partial pressure in the later stage, which was more conducive to conversion of propionic acid. The microscopic analysis indicated that NZVI could flocculate and adsorb on the extracellular polymeric substances (EPS) around the anaerobic microorganisms, protecting most active microbial cell membrane from contact damage. On the other hand, some decaying microbial cells membrane could be destroyed by NZVI and intracellular substances would be released due to the reduction of EPS.

3.
Plant J ; 101(1): 188-203, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31529551

RESUMO

CG methylation (m CG) is essential for preserving genome stability in mammals, but this link remains obscure in plants. OsMET1-2, a major rice DNA methyltransferase, plays critical roles in maintaining m CG in rice. Null mutation of OsMET1-2 causes massive CG hypomethylation, rendering the mutant suitable to address the role of m CG in maintaining genome integrity in plants. Here, we analyzed m CG dynamics and genome stability in tissue cultures of OsMET1-2 homozygous (-/-) and heterozygous (+/-) mutants, and isogenic wild-type (WT). We found m CG levels in cultures of -/- were substantially lower than in those of WT and +/-, as expected. Unexpectedly, m CG levels in 1- and 3-year cultures of -/- were 77.6% and 48.7% higher, respectively, than in shoot, from which the cultures were initiated, suggesting substantial regain of m CG in -/- cultures, which contrasts to the general trend of m CG loss in all WT plant tissue cultures hitherto studied. Transpositional burst of diverse transposable elements (TEs) occurred only in -/- cultures, although no elevation of genome-wide mutation rate in the form of single nucleotide polymorphisms was detected. Altogether, our results establish an essential role of m CG in retaining TE immobility and hence genome stability in rice and likely in plants in general.

4.
Cell Biochem Funct ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31797406

RESUMO

Cataract is the leading cause of blindness in the world while the molecular mechanisms of cataracts pathogenesis are not well elucidated. Dysregulated microRNA (miRNA) expressions have been implicated in cataract. However, the precise role of miR-4328 in cataract is still unknown. We compared the expression level of total miR-4328 between clinical samples from healthy people and cataract patient and between UV-irradiated and control lens epithelial cells. We determined the effect of miR-4328 on lens epithelial cell proliferation and apoptosis by suppressing miR-4328. We further predicted NLR Family Apoptosis Inhibitory Protein (NAIP) as potential target of miR-4328 and continued to evaluate the effects of NAIP on cell proliferation and apoptosis. MiR-4328 was up-regulated in cataract sample and in UV-irradiated lens epithelial cells. Suppressing MiR-4328 promoted cell proliferation and inhibited apoptosis. MiR-4328 targeted NAIP and suppressed its expression. Knocking down NAIP abolished the effects of miR-4328 on cell proliferation and inhibited apoptosis. MiR-4328 promotes lens epithelial cell apoptosis by targeting NAIP in age-related cataract. SIGNIFICANCE OF THE STUDY: MiR-4328 targeted NAIP and suppressed its expression. Knocking down NAIP abolished the effects of miR-4328 on cell proliferation and inhibited apoptosis. MiR-4328 promotes lens epithelial cell apoptosis by targeting NAIP in age-related cataract.

5.
Front Plant Sci ; 10: 1541, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31827481

RESUMO

One of the extraordinary aspects of plant genome evolution is variation in chromosome number, particularly that among closely related species. This is exemplified by the cotton genus (Gossypium) and its relatives, where most species and genera have a base chromosome number of 13. The two exceptions are sister genera that have n = 12 (the Hawaiian Kokia and the East African and Madagascan Gossypioides). We generated a high-quality genome sequence of Gossypioides kirkii (n = 12) using PacBio, Bionano, and Hi-C technologies, and compared this assembly to genome sequences of Kokia (n = 12) and Gossypium diploids (n = 13). Previous analysis demonstrated that the directionality of their reduced chromosome number was through large structural rearrangements. A series of structural rearrangements were identified comparing the de novo G. kirkii genome sequence to genome sequences of Gossypium, including chromosome fusions and inversions. Genome comparison between G. kirkii and Gossypium suggests that multiple steps are required to generate the extant structural differences.

6.
Thorac Cancer ; 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31828980

RESUMO

BACKGROUND: The impact of adjuvant treatment for esophageal carcinoma with tumor-negative lymph nodes after upfront radical esophagectomy is still uncertain. This study investigated the effects of postoperative radiotherapy in pT1-3N0 esophageal carcinoma after radical resection. METHOD: We retrospectively identified pT1-3N0M0 esophageal carcinoma patients between 2000 and 2016 from the Surveillance, Epidemiology, and End Results database. Patients with upfront esophagectomy were categorized as having received surgery alone (SA) and surgical resection followed by adjuvant radiotherapy (SA + RT). Propensity score matching, univariate and multivariate analysis were performed to compare overall survival (OS) and cause-specific survival (CSS). RESULTS: A total of 2862 patients were identified, of whom 274 received SA + RT and 2588 received SA. The median follow-up was 60.4 months (95%CI, 58.7-62.1 months). The five-year OS and CSS were better for SA group compared with SA + RT group (P < 0.001, respectively). Furthermore, after matching, the OS and CSS were still significantly better for SA patients. For T subgroup analysis, postoperative radiotherapy was an independent prognostic factor only for pT1 patients with worse OS, without survival differences for pT2 and pT3 patients. However, after multivariate cox analysis, postoperative radiotherapy can provide significantly better OS for pT3 patients with tumor length ≥5 cm (P = 0.03; 95%CI, 0.29-0.94). CONCLUSIONS: Among pT1-3N0M0 esophageal carcinoma patients, postoperative radiotherapy can provide significantly better OS for pT3 patients with tumor length ≥5 cm. However, there are no survival benefits for pT1-2 patients after SA + RT procedure. This finding may have significant implications on the use of adjuvant radiation in patients with pN0 disease.

7.
Med Chem ; 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31880252

RESUMO

BACKGROUND: NEDD8 activating enzyme (NAE) plays a critical role in various cellular functions in carcinomas. The selective inhibition of NAE could mediate the rate of ubiquitination and the subsequent degradation of proteins associated with cancer so as to achieve the purpose of treatment. OBJECTIVE: In this article, we decided to study the synthesis and screening of 4-amino substituted 2H-chromen-2-one derivatives against cancer cell lines, specifically the human pancreatic cancer cell line BxPC-3. METHODS: After synthesis of twenty targeted compounds, we evaluated their anti-proliferative activity against six cancer cell lines, cytotoxicity against three normal cell lines through MTT assay and hemolysis to screen out the candidate compound, which was further conducted drug-like physical property measurement, target confirmation by enzyme-based experiment, cell apoptosis and synergistic effect research. RESULTS: Starting from intermediate 4 and 5 several new 4-amino substituted 2H-chromen-2-one derivatives (9-28) were synthesized and evaluated for their cell activities using six cancer cell lines. We performed test of cytotoxicity, hemolysis, ATP-dependent NAE inhibition in enzyme-based system, apoptosis and synergistic effect in BxPC-3 cells against the best candidate compound 21. CONCLUSION: Based on these results, we found that compound 21 inhibited NAE activity in an ATP-dependent manner in enzyme-based system, induced apoptosis in BxPC-3 cells and synergized with bortezomib on BxPC-3 cell growth inhibition. Additionally, it had low toxicity with reasonable Log P value and water solubility.

8.
Chem Sci ; 10(35): 8246-8252, 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31673325

RESUMO

Photothermal therapy in the second near-infrared window (NIR-II, 1000-1700 nm) exhibits a significant advantage over the first near-infrared window (NIR-I, 650-950 nm) in terms of both maximum permissible exposure (MPE) and penetration depth. However, the thus far reported NIR-II photothermal agents (PTAs) have been focused just on inorganic semiconducting and organic polymeric semiconducting nanoparticles. Herein a novel cruciform phthalocyanine pentad was designed, synthesized, and characterized for the first time. The water-soluble nanoparticles (Zn4-H2Pc/DP NPs) assembled from this single molecular material with the help of DSPE-PEG2000-OCH3 exhibit characteristic absorption in the NIR-II region at 1064 nm with a large extinction coefficient of 52 L g-1 cm-1, high photothermal conversion efficiency of 58.3%, and intense photoacoustic signal. Moreover, both in vitro and in vivo studies reveal the good biocompatibility and notable tumor ablation ability of Zn4-H2Pc/DP NPs under 1064 nm laser irradiation. Theoretical density functional theory calculations interpret the two-dimensional compressional wave energy-dissipation pathway over the broad saddle curved framework of the cruciform conjugated phthalocyanine pentad, rationalizing the efficient photothermal properties of corresponding Zn4-H2Pc/DP NPs in the NIR-II window.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31718418

RESUMO

Background: Although minimally invasive pancreatic necrosectomy (MIPN) is a new invasive technique for necrotizing pancreatitis, it has some disadvantages. This study aimed to improve the debridement technique with an ultrasonic pressure ballistic system. We hypothesized that this system would facilitate debridement and improve the safety of the procedure. Materials and Methods: Between October 2016 and January 2019, 5 patients diagnosed with necrotizing pancreatitis were enrolled in the clinical cohort. All patients underwent debridement due to infective necrosis. Access for debridement was typically established with percutaneous puncture. Then MIPN was performed. During the procedure, ultrasonic pressure was applied to liquefy the necrotic material and make it absorbable. The effect of debridement was assessed by analyzing the average bleeding volume, operation time, and complications. Postoperative clinical parameters were evaluated. Results: Debridement was performed successfully for all patients. Semisolid necrotic tissue was dissolved with ultrasonic pressure. Viscous pus was rapidly aspirated with the suction applied with negative pressure, which greatly enhanced efficiency. This approach enhanced the visibility of blood vessels, which improved safety. No major complications were encountered. Two patients (40%) developed puncture site infections. The average blood loss during the operation was 13 ± 6 mL. The average operation time was 78 ± 31 minutes. Postoperative APACHE II scores were significantly lower than preoperative scores (P < .05). White blood cells, C-reactive protein, and procalcitonin levels declined postoperatively. Conclusions: The ultrasonic pressure ballistic system could potentially enhance MIPN and make it safer.

10.
Mol Genet Genomic Med ; 7(12): e1022, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31692290

RESUMO

BACKGROUND: Pituitary adenomas (PAs) are one of the most common intracranial tumors; approximately half of PAs are prolactin (PRL)-secreting PAs (prolactinomas). The genetic alterations prevalent in prolactinomas are unknown. METHODS: Here, we present a patient with an extremely aggressive and giant prolactinoma accompanied by serious destruction of the surrounding bone mass. This patient exhibited resistance to dopaminergic drugs. Through whole-genome sequencing, we identified two novel somatic mutations in the POU6F2 gene (NM_001166018.2: c. 839 C>T; NM_001166018.2: c. 875A>G). RESULTS: This report is the first to identify these somatic mutations in the POU6F2 gene in a prolactinoma. We found that these two mutations obviously decreased the expression level of POU6F2. Inhibition of POU6F2 activity increased the cell proliferation and PRL secretion in rat pituitary cells, but proliferation and PRL secretion were decreased in cells with POU6F2 overexpression. CONCLUSIONS: POU6F2 might play a crucial role in the development of prolactinomas and may be a promising target for developing new therapies against prolactinomas.

11.
Front Microbiol ; 10: 2167, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31611849

RESUMO

Two new species (Melanoleuca galerina and M. subgrammopodia) and seven new recorded species from northern China are described here using morphological and molecular methods. Melanoleuca galerina is mainly characterized by its hygrophanous pileus, decurrent lamellae, fibrous stipe and spores with round warts. Key characteristics of M. subgrammopodia include its discolored pileus, fibrous stipe and urticiform cystidia. The divergence time of Melanoleuca fungi as well as the phylogenetic relationships within this genus were analyzed using DNA sequences of the internal transcribed spacer (ITS) and the nuclear large subunit rDNA (nrLSU) gene fragments. Analyses revealed that morphological identifications and phylogenetic relationships were consistent with the results of divergence time, thereby confirming that M. galerina and M. subgrammopodia are new species.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31613776

RESUMO

Genome sequencing is one of the most challenging problems in computational biology and bioinformatics. As a traditional algorithm, the string match meets a challenge with the development of the massive volume of data because of gene sequencing. Surveys show that there will be a huge amount of short read segments during the process of gene sequencing and the need for a highly efficient is urgent. As a classic fast and exact single pattern matching algorithm, Knuth-Morris-Pratt (KMP) algorithm has been demonstrated in network security and computational biology. However, with the increasing amount of data in the modern society, it becomes increasingly important and essential to provide a High-performance implementation of KMP algorithm. In this paper, we implement a scalable KMP accelerator based on FPGA, named GeneKMP. The accelerator is composed of different computing units to achieve a pipelined organization for higher throughput with satisfying scalability. A novel programming model is provided to alleviate the burden of the high-level programmers. We provide a greedy-based partitioning algorithm for the software/hardware design paradigms. Experimental results on the state-of-the-art Xilinx FPGA hardware prototype show that our accelerator can achieve up to a promising speedup with insignificant hardware cost and power consumption.

13.
Chemistry ; 25(71): 16207-16213, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31602719

RESUMO

The functionalization of natural 1D architectures is dependent on hierarchically inner nanostructures. However, the artificial supramolecular nanofibers or nanotubes were rarely developed with complex inner structures. Inspired by a biomimetic strategy, single-molecule-diameter nanofibers of double-decker phthalocyanine (EuPc2) with compartmentalized internal space and fantastic electrochemical features were developed upon air/water interfacial assembly with poly-l-lysine. EuPc2/poly-l-lysine nanofibers can be electrochemical sensors both in water and the gas phase and have the best analytical performances for nitrite among all the porphyrins or phthalocyanines monomers and assemblies. Imbedding nitrite in compartments not only promotes the sensing but also changes the supramolecular chirality of nanofibers, and the morphological-dependent sensing properties of EuPc2 assemblies in water are different from that in the gas phase. These results suggest the unprecedented properties for diverse applications of artificial 1D architectures containing complex inner nanostructures.

14.
Biomed Pharmacother ; 120: 109352, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586905

RESUMO

Inflammatory monocyte and macrophage subset accumulation during the inflammatory response that drives atherosclerosis can exacerbate the extent of atherosclerosis. It has been demonstrated that voltage-gated sodium channels (VGSCs) can regulate cell bioactivities in monocytes/macrophages. We hypothesized that blockade of mononuclear phagocyte VGSCs was atheroprotective through monocyte/macrophage subset modulation and macrophage proliferation suppression in atherosclerotic lesions. In this experimental study, when VGSCs were knocked down with RNA interference plasmid transfection in mouse peripheral blood monocytes and monocyte-macrophage lineage RAW264.7 cells in vitro, the biological characteristics of proliferation, phagocytosis, and migration in RAW264.7 cells declined. In addition, suppression of LPS-induced M1 polarization and facilitation of IL-4-induced M2 polarization were also observed. In an in vivo study, ApoE knockout (ApoE-/-) mice were fed a standard chow diet (CD) or a western diet (WD). After feeding with phenytoin (PHT), no significant differences were detected in plasma lipids, and the anti-inflammatory phenotypes of both monocytes and macrophages were elevated and proinflammatory phenotypes declined. The local proliferation of macrophages was also distinctly suppressed, along with a significant reduction in atheromatous plaques. In conclusion, blockade of VGSCs in the mononuclear phagocyte system reduced atherosclerotic lesions, which may occur through altering monocyte/macrophage subsets and suppressing macrophage proliferation in atherosclerotic plaques. Blockage of VGSCs may play an important role in cardiovascular protection.

15.
Thorac Cancer ; 10(11): 2161-2167, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31556243

RESUMO

BACKGROUND: In recent years, diagnosis of early squamous cell carcinoma of the esophagus has been increasingly emphasized. The application of endoscopic submucosal dissection (ESD) has enabled safe resection of esophageal lesions. Minimally invasive esophagectomy (MIE) is also safe and feasible for early stages of the cancer. This study aimed to compare the therapeutic effects of early esophageal carcinoma treatment, and find the best predictive factor for the selection of treatment for T1a patients. METHODS: We performed a retrospective study of early-stage patients admitted to Tianjin Medical University Cancer Institute and Hospital between January 2015 and December 2018. A total of 128 patients underwent MIE, while 78 patients underwent ESD. The depth of the tumor invasion, lymph node metastasis, and complications were compared between the two groups. RESULTS: In the ESD group, 76.92% of the patients were stage T1a, while 34.38% in the MIE group were stage T1a. The lymph node metastasis rate was 16.41% in the MIE group (6.98% in T1a stage), which related to tumor differentiation, tumor length (≥37.5 mm), depth of invasion, and angiolymphatic invasion. However, the R0 resection rate was only 73.08% in the ESD group. Comprehensive analysis of all T1 patients in the two groups revealed that the positive margin was related to tumor differentiation, tumor width (≥13.5 mm), and depth of invasion (≥3.25 mm). CONCLUSION: For early-stage cases, lymph node metastasis and positive margins are risk factors affecting long-term survival. Efficient predictive factors mentioned in our study would provide a proper indication for treatment strategy selection.

16.
Front Oncol ; 9: 809, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31508369

RESUMO

Advances in the understanding of growth hormone-producing adenomas (GHomas) are ongoing, but current therapy is limited by moderate and variable efficacy and in need of life-long treatment. In this study, the molecular signaling pathway related to GHoma was investigated by proteomics and transcriptomics. The differentially expressed proteins and genes were significantly enriched in Extracellular Matrix-Receptor Interactions, Notch Signaling, Basal Cell Carcinoma Signaling, JAK-STAT3, Wnt Signaling, and Glioblastoma Multiforme Signaling by Ingenuity Pathway Analysis. Furthermore, the Notch2/Delta-like canonical Notch ligand (DLL) signaling pathway was identified to be associated with tumorigenesis and invasiveness of GHoma. In 76 patients, Notch2 and DLL3 were upregulated in invasive compared to those in non-invasive GHoma (p < 0.05). Disease-free survival was significantly longer in patients with low, compared with high, DLL3 expression (p = 0.027). Notch 2 knockdown inhibited cell migration in both GH3 cells and primary GHoma cells, along with downregulation of the mRNA expression of related genes. DAPT, a γ-secretase inhibitor, inhibited tumor growth and invasion in vivo and in vitro and suppressed the release of growth hormone in primary GHoma cells. The involvement of Notch2/DLL3 signaling in GHoma progression warrants additional study of Notch inhibitor, DAPT, as a potential GHoma treatment. Importance of the Study: Current treatments of GH adenomas (GHomas) are limited by their moderate and variable efficacy and in need of life-long treatment. We found that the Notch2/Delta-like Notch ligand 3 (DLL3) signaling pathway was active in GHoma tumorigenesis, progression, and invasion.The γ-secretase inhibitor DAPT is of potential use in GHoma treatment targeting Notch signaling.

17.
Environ Technol ; : 1-10, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31560610

RESUMO

With their wide application, some nanomaterials entering into the environment and made effects in many ways. Different concentrations of Fe3O4 nanoparticles (NPs) were added (0, 100, 200, 400 and 600 mg/L) in this study, the changes of substance in three stages of anaerobic digestion (AD) were explored, the optimal dosage of Fe3O4 NPs was finally found. The results showed that the 200 mg/L Fe3O4 NPs could better promote the decomposition of organic matter than the other groups, the protein and polysaccharide degradation rate reached to 99.75% and 83.14%, respectively. In the acidogenesis stage, the acetic acid concentration reached up to 692.88 mg/L, increased by 31.8% compared with the control group. Fe3O4 NPs had also been proved to increase VFAs, finally made the methane content reach to 92.22%. The variation of coenzyme F420 had also been described in this research, the highest value was 1.83 Umol/g VS. These results showed that the different concentrations of Fe3O4 NPs had different effects on anaerobic digestion.

18.
Opt Lett ; 44(18): 4617, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31517945

RESUMO

In this erratum, the function z(θ) in equation (7) of Opt. Lett.44, 2843 (2019)OPLEDP0146-959210.1364/OL.44.002843 has been corrected.

19.
Med Gas Res ; 9(3): 122-126, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31552874

RESUMO

Cognitive deficits are a devastating neurological outcome seen in survivors of cardiac arrest. We previously reported water electrolysis derived 67% hydrogen gas inhalation has some beneficial effects on short-term outcomes in a rat model of global brain hypoxia-ischemia induced by asphyxia cardiac arrest. In the present study, we further investigated its protective effects in long-term spatial learning memory function using the same animal model. Water electrolysis derived 67% hydrogen gas was either administered 1 hour prior to cardiac arrest for 1 hour and at 1-hour post-resuscitation for 1 hour (pre- & post-treatment) or at 1-hour post-resuscitation for 2 hours (post-treatment). T-maze and Morris water maze were used for hippocampal memory function evaluation at 7 and 14 days post-resuscitation, respectively. Neuronal degeneration within hippocampal Cornu Ammonis 1 (CA1) regions was examined by Fluoro-Jade staining ex vivo. Hippocampal deficits were detected at 7 and 18 days post-resuscitation, with increased neuronal degeneration within hippocampal CA1 regions. Both hydrogen gas treatment regimens significantly improved spatial learning function and attenuated neuronal degeneration within hippocampal CA1 regions at 18 days post-resuscitation. Our findings suggest that water electrolysis derived 67% hydrogen gas may be an effective therapeutic approach for improving cognitive outcomes associated with global brain hypoxia-ischemia following cardiac arrest. The study was approved by the Animal Health and Safety Committees of Loma Linda University, USA (approval number: IACUC #8170006) on March 2, 2017.

20.
Br J Cancer ; 121(8): 640-646, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31523058

RESUMO

BACKGROUND: Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies. METHODS: Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate. RESULTS: Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand-foot syndrome, increased L-gamma-glutamyltransferase. CONCLUSIONS: Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted. TRIAL REGISTRATION: NCT02945852.

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