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1.
Chemistry ; 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33090581

RESUMO

The crystal interaction density is generally assumed to be a suitable measure of the polarization of a low-molecular weight ligand inside an enzyme, but this approximation has seldomly been tested and has never been quantified before. In this study, we compare the crystal interaction density and the interaction electrostatic potential for a model compound of loxistatin acid (E64c) with those inside cathepsin B, in solution and in vacuum. We apply QM/MM calculations and experimental quantum crystallography to show that the crystal interaction density is indeed very similar to the enzyme interaction density. Less than 0.1e are shifted between these two environments in total. However, this has non-negligible consequences for derived properties.

2.
BMC Genomics ; 21(1): 711, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054712

RESUMO

BACKGROUND: Genes are regulated by various types of regulators and most of them are still unknown or unobserved. Current gene regulatory networks (GRNs) reverse engineering methods often neglect the unknown regulators and infer regulatory relationships in a local and sub-optimal manner. RESULTS: This paper proposes a global GRNs inference framework based on dictionary learning, named dlGRN. The method intends to learn atomic regulators (ARs) from gene expression data using a modified dictionary learning (DL) algorithm, which reflects the whole gene regulatory system, and predicts the regulation between a known regulator and a target gene in a global regression way. The modified DL algorithm fits the scale-free property of biological network, rendering dlGRN intrinsically discern direct and indirect regulations. CONCLUSIONS: Extensive experimental results on simulation and real-world data demonstrate the effectiveness and efficiency of dlGRN in reverse engineering GRNs. A novel predicted transcription regulation between a TF TFAP2C and an oncogene EGFR was experimentally verified in lung cancer cells. Furthermore, the real application reveals the prevalence of DNA methylation regulation in gene regulatory system. dlGRN can be a standalone tool for GRN inference for its globalization and robustness.

3.
Ther Apher Dial ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33012089

RESUMO

HD care may experience great stress with the coronavirus disease 2019 (COVID-19) pandemic. A modified HD modality named bed-sided short-duration renal replacement therapy (BSRRT) was used in noncritical maintenance HD (MHD) patients diagnosed with COVID-19 in Wuhan due to extreme situation. To determine the safety and efficacy as a substitution for intermittent HD (IHD), we conducted this study. We used the data of 88 noncritical COVID-19 MHD patients collected from 65 medical units at the hospitals in Wuhan, China, from January 1 to March 10, 2020. t-test, Wilcoxon rank sum test, and Fisher exact probability method were used to compare the baseline characteristics, treatment, and death. Log-rank test and Cox regression multivariate analysis was used to compare the survival of noncritical patients who were transferred to BSRRT modality versus those who were continued on the IHD. Univariate analysis showed the level of reported fatigue symptom at present, bilateral lung computed tomography infiltration and steroid treatment differed between the two groups. The outcome of death of the two groups did not show significant differences in univariate analysis (P = .0563). Multivariate Cox regression analysis dialysis showed modality of treatment after COVID-19 diagnosis was not a significant predictor of death (P = .1000). These data suggest that for noncritical COVID-19 MHD patients, the transfer from IHD to BSRRT does not have significant difference in the risk of death compared with IHD group. This finding suggests this modified modality could be an option for the substitution for IHD during the COVID-19 pandemic period.

4.
Cancer Lett ; 497: 89-99, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33038492

RESUMO

The human genome contains thousands of noncoding RNAs (ncRNAs), which are thought to lack open reading frames (ORFs) and cannot be translated. Some ncRNAs reportedly have important functions, including epigenetic regulation, chromatin remolding, protein modification, and RNA degradation, but the functions of most ncRNAs remain elusive. Through the application and development of ribosome profiling and sequencing technologies, an increasing number of studies have discovered the translation of ncRNAs. Although ncRNAs were initially defined as noncoding RNAs, a number of ncRNAs actually contain ORFs that are translated into peptides. Here, we summarize the available methods, tools, and databases for identifying and validating ncRNA-encoded peptides/proteins, and the recent findings regarding ncRNA-encoded small peptides/proteins in cancer are compiled and synthesized. Importantly, the role of ncRNA-encoding peptides/proteins has application prospects in cancer research, but some potential challenges remain unresolved. The aim of this review is to provide a theoretical basis that might promote the discovery of more peptides/proteins encoded by ncRNAs and aid the further development of novel diagnostic and prognostic cancer markers and therapeutic targets.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33095455

RESUMO

OBJECTIVES: Nutrition status is of great significance to the clinical outcome after major abdominal surgery. However, the effect of preoperative short-term parenteral nutrition (PN) support among gastric cancer (GC) patients remains unknown and was evaluated in the current study. METHODS: We retrospectively analyzed 455 nutritionally at-risk GC patients after radical resection from 2010 to 2016. We matched patients with 3-7 days of PN support to those without PN support. χ2 And Mann-Whitney U tests were used to compare differences between the PN and control groups. RESULTS: The propensity-matched sample included 368 GC patients (PN group, n = 184; control group, n = 184). The PN and control groups did not differ regarding postoperative complications (P = .528). The incidence of anastomotic leakage in the PN group was lower than in the control group (P = .011), whereas other complications were not found to differ between the groups. The hospitalization cost of the PN group was significantly higher than that of the control group (P < .001), whereas other outcome indicators were similar. Subgroup analysis showed that short-term PN support may have an improved benefit for patients with serum albumin level <35 g/L, but not at the level of statistical significance (P = .17). CONCLUSION: Short-term PN support did not significantly improve the short-term clinical outcomes of nutritionally at-risk GC patients, with the exception of a lower incidence of anastomotic leakage. Considering that short-term PN support increases economic burden, PN should not be the preferred method among these patients.

6.
J Stroke Cerebrovasc Dis ; 29(12): 105335, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007680

RESUMO

BACKGROUND AND PURPOSE: Modified Thrombolysis in Cerebral Infarction (mTICI)2b/3 has been considered the criterion for successful reperfusion in endovascular treatment. This study aimed to compare the therapeutic safety and efficacy of mTICI2b and mTICI3 recanalization, and to analyze the factors related to outcomes in everyday clinical practice. MATERIALS AND METHODS: This is a single-center retrospective analysis of 224 patients who underwent successful thrombectomy (achieving a mTICI score ≥2b). The primary outcomes included a modified Rankin score (mRS) of 0-2 at 90-day, mortality, and symptomatic intracranial hemorrhage. RESULTS: A total of 111 patients achieved mTICI2b status (49.6%), and 113 achieved mTICI3 status (50.4%). The comparison between mTICI2b and 3 reperfusions showed no differences in short-term outcomes, 90-day mRS, complications, and mortality. There was a trend toward more passes in mTICI2b patients, although the difference was not significant. The univariate analysis showed that poor outcomes after endovascular treatment were associated with older age, previous history of coronary heart disease, atrial fibrillation, diabetes, tandem occlusions, high National Institutes of Health Stroke Scale (NIHSS) score on admission, and general anesthesia. A previous history of coronary heart disease, a high NIHSS score on admission, and the use of general anesthesia were independent factors that affected the therapeutic effects. CONCLUSION: The superiority (efficacy and safety) of mTICI3 reperfusion was not significant compared with that of mTICI2b reperfusion. Prolonged efforts to achieve mTICI3 after achieving mTICI2b should be considered prudently for those with difficulty achieving 100% reperfusion.

7.
Cancer Sci ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016509

RESUMO

Prolonged hypersecretion of catecholamine induced by chronic stress may correlate with malignant progression of cancer. ß2-adrenergic receptor (ß2-AR) overexpressed in certain cancer cells may translate the signals from neuroendocrine system to malignant signals by interacting with oncoproteins, such as Her2. In the present study, we demonstrate that catecholamine stimulation activates the expression and proteolytic activity of ADAM10 by modulating the expression of miR-199a-5p and SIRT1 and also confirm that catecholamine induction triggers the activities of γ-secretase, leading to shedding of Her2 extracellular domain (ECD) by ADAM10 and subsequent intramembranous cleavage of Her2 intracellular domain (ICD) by presenilin-dependent γ-secretase, nuclear translocation of Her2 ICD, and enhanced transcription of tumor metastasis-associated gene COX-2. Chronic stimulation of catecholamine strongly promotes the invasive activities of cancer cells in vitro and spontaneous tumor lung metastasis in mice. Furthermore, nuclear localization of Her2 was significantly correlated with overexpression of ß2-AR in human breast cancer tissues, indicating that catecholamine-induced ß2-AR activation plays decisive roles in tumor metastasis. Our data also reveal that an unknown mechanism by which the regulated intramembrane proteolysis (RIP) initiated by ß2-AR-mediated signaling controls a novel Her2-mediated signaling transduction.

8.
Pharm Dev Technol ; : 1-9, 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33070673

RESUMO

Multidrug resistance (MDR) is a serious challenge in chemotherapy and also a major threat to breast cancer treatment. As an intracellular energy factory, mitochondria provide energy for drug efflux and are deeply involved in multidrug resistance. Mitochondrial targeted delivery of doxorubicin can overcome multidrug resistance by disrupting mitochondrial function. By incorporating a reactive oxygen species (ROS)-responsive hydrophobic group into the backbone structure of hyaluronic acid - a natural ligand for the highly expressed CD44 receptor on tumor surfaces, a novel ROS-responsive and CD44-targeting nano-carriers was constructed. In this study, mitochondria-targeted triphenylphosphine modified-doxorubicin (TPP-DOX) and amphipathic ROS-responsive hyaluronic acid derivatives (HA-PBPE) were synthesized and confirmed by 1H NMR. The nanocarriers TPP-DOX @ HA-PBPE was prepared in a regular shape and particle size of approximately 200 nm. Compared to free DOX, its antitumor activity in vitro and tumor passive targeting in vivo has been enhanced. The ROS-responsive TPP-DOX@HA-PBPE nanocarriers system provide a promising strategy for the reverse of MDR and efficient delivery of doxorubicin derivatives into drug-resistant cancer cells.

9.
Orthop Surg ; 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33073506

RESUMO

OBJECTIVE: To compare the clinical outcomes of horizontal mattress suture vs free-edge suture in the all-inside arthroscopic Broström-Gould procedure. METHODS: This retrospective cohort study included 68 chronic lateral ankle instability (CLAI) patients who underwent either a horizontal mattress suture or a free-edge suture all-inside arthroscopic Broström-Gould procedure from January 2014 to January 2017. Patients were divided into two groups based on the suture fashion during the all-inside arthroscopic Broström-Gould procedure. In the horizontal mattress suture group (n = 31), anchor sutures were used to suture the ATFL, capsule, and inferior extensor retinaculum in horizontal mattress suture fashion. In the free-edge suture group (n = 37), anchor sutures were used to suture the ATFL, capsule, and inferior extensor retinaculum in free-edge suture fashion. The Visual Analogue Scale (VAS) score, the American Orthopaedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (KAFS), Anterior Talar Translation (ATT), the rate of return to sports, and ankle proprioceptive recovery were compared in both groups. RESULTS: The operative times and duration of hospitalization between the two groups were comparable (all P > 0.05). The VAS, AOFAS, ATT, the rate of return to sports, and ankle proprioceptive recovery were comparable between the horizontal mattress suture and free-edge suture groups at 1 and 2 years after surgery. Patients of the free-edge suture group achieved better KAFS 1 and 2 years after the surgery compared with those of the horizontal mattress suture group. In both groups, incisions were healed by first intention, and complications such as infection, implant reactions, tendon injury, and nervous or vascular injuries were not observed. The ankle proprioceptive recovery in horizontal mattress suture and free-edge suture groups showed no significant differences at 1 and 2 years after surgery. The mean time of the return to full activity for patients in the horizontal mattress suture group was 10.38 ± 2.02 (range 8 to 12) weeks vs 8.63 ± 2.31 (range 8 to 12) weeks for those in the free-edge suture group (P = 0.001, power = 0.907). The exercise participation rates were comparable between groups (P > 0.05). At the 2-year follow-up, all patients regained normal activities and ankle stability, and no recurrence of CLAI or revision surgery was recorded. CONCLUSION: All-inside arthroscopic Broström-Gould surgery for the treatment of CLAI ensures a better functional effect (KAFS) and better recovery time when free-edge suture is used instead of horizontal mattress suture.

10.
JAMA Ophthalmol ; 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001210

RESUMO

Importance: Because studies have suggested that atropine might slow the progression of myopia in children, randomized clinical trials are warranted to understand this potential causal relationship. Objective: To evaluate the efficacy and safety of atropine, 0.01%, eyedrops on slowing myopia progression and axial elongation in Chinese children. Design, Setting, and Participants: This was a randomized, placebo-controlled, double-masked study. A total of 220 children aged 6 to 12 years with myopia of -1.00 D to -6.00 D in both eyes were enrolled between April 2018 and July 2018 at Beijing Tongren Hospital, Beijing, China. Cycloplegic refraction and axial length were measured at baseline, 6 months, and 12 months. Adverse events were also recorded. Interventions: Patients were randomly assigned in a 1:1 ratio to atropine, 0.01%, or placebo groups to be administered once nightly to both eyes for 1 year. Main Outcomes and Measures: Mean changes and percentage differences in myopia progression and axial elongation between atropine, 0.01%, or placebo groups. Results: Of 220 participants, 103 were girls (46.8%), and the mean (SD) age was 9.64 (1.68) years. The mean (SD) baseline refractive error and axial length were -2.58 (1.39) D and 24.59 (0.87) mm. Follow-up at 1 year included 76 children (69%) and 83 children (75%) allocated into the atropine, 0.01%, and placebo groups, respectively, when mean myopia progression was -0.49 (0.42) D and -0.76 (0.50) D in the atropine, 0.01%, and placebo groups (mean difference, 0.26 D; 95% CI, 0.12-0.41 D; P < .001), with a relative reduction of 34.2% in myopia progression. The mean (SD) axial elongation in the atropine, 0.01%, group was 0.32 (0.19) mm compared with 0.41 (0.19) mm in the placebo group (mean difference, 0.09 mm; 95% CI, 0.03-0.15 mm; P = .004), with relative reduction of 22.0% in axial elongation. Fifty-one percent and 13.2% of children progressed by at least 0.50 D and 1.00 D in the atropine, 0.01%, group, compared with 69.9% and 34.9% in the placebo group. No serious adverse events related to atropine were reported. Conclusions and Relevance: While the clinical relevance of the results cannot be determined from this trial, these 1-year results, limited by approximately 70% follow-up, suggest that atropine, 0.01%, eyedrops can slow myopia progression and axial elongation in children and warrant future studies to determine longer-term results and potential effects on slowing sight-threatening pathologic changes later in life. Trial Registration: http://www.chictr.org.cn Identifier: ChiCTR-IOR-17013898.

11.
Mol Carcinog ; 59(11): 1269-1279, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32914490

RESUMO

Despite considerable knowledge of viral pathogenesis, the pathophysiological changes related to the multifactorial, multistep process of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) development remains unclear. Longitudinal metabolomics study can reveal biological process for disease progression. We performed metabolite profiling with longitudinal prediagnostic plasma samples from two nested case-control studies of hepatitis B surface antigen carriers participating in ultrasound screening for HCC, one within a government employee cohort (870 samples from 109 HCC cases and 107 controls) and the other within a hospital-based cohort (266 samples from 63 HCC cases and 114 controls). Of the 34 measured metabolites, tyrosine, isoleucine, and glutamine were consistently associated with HCC. In analyses combining longitudinal data, a high metabolic risk score based on the three amino acids was robustly associated with increased risk of HCC (OR = 3.71, 95% confidence interval: 2.53-5.42), even after adjustment for clinical factors, or when assessed for different times up to ≥8 years before diagnosis. Similar association was observed in an independent, prospective analysis comprising 633 randomly selected individuals of the government employee cohort. More importantly, this metabolite signature was longitudinally influenced by HBV-infection phase and involved in gradual progression to liver fibrosis and cirrhosis. Furthermore, mediation analysis showed that the score mediated substantial proportions of the associations of key viral factors, insulin resistance, and diabetes status with HCC risk. Our results suggest that an amino-acid dysregulation metabotype may play a role in HBV-related HCC development, and may also be linked to common pathways that mediate increased HCC risks.

13.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(8): 719-723, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32958129

RESUMO

Objective To observe the changes of the acetylation of lysine 9 on histone H3 (H3K9) and H3K14 in the different brain regions during rapid eye movement after sleep deprivation (SD) in rats. Methods Modified multiple platform was used to establish the SD model. Forty-eight rats were randomly divided into four groups: control group, one day post-SD group (SD1), three day post-SD group (SD3) and six day post-SD group (SD6). Western blotting was performed to examine the changes in the acetylation levels of H3K9 and H3K14 in different brain regions, including hippocampus, hypothalamus, prefrontal cortex and raphe nucleus. Results Compared with the control group, in the SD1, SD3, and SD6 groups, the acetylation levels of H3K9 and H3K14 in the hippocampus and hypothalamus significantly decreased time-dependently. In contrast, their levels in the ventromedial prefrontal cortex and raphe nucleus markedly increased in the SD6 but not in the SD1 and SD3 groups. Conclusion The increase of H3K9 and H3K14 acetylation in the hippocampus and hypothalamus as well as the decrease of H3K9 and H3K14 acetylation in the prefrontal cortex and raphe nucleus may be involved in the development of sleep disorders.

14.
J Environ Sci Health B ; : 1-7, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32897819

RESUMO

Micro RNAs (miRNAs) are major players in cellular responses to xenobiotic compounds and toxins. However, their functions in organophosphate-induced cytotoxicity remain unclear. This study investigated the involvement of miR-96-5p in the non-cholinergic toxicity of malathion in normal human kidney cells (HK-2 cells). Malathion decreased HK-2 cell viability and the expression of miR-96-5p in a dose- and time-dependent manner. In addition, transfection with miR-96-5p mimics attenuated malathion-induced HK-2 cell apoptosis, whereas transfection with a miR-96-5p inhibitor increased HK-2 cell apoptosis. Luciferase assays indicated that miR-96-5p could bind directly to the 3'-untranslated region of DDIT3, a well-known marker of endoplasmic reticulum stress. Further analyses of the expression of apoptosis-related genes and proteins indicated that miR-96-5p may function to reduce malathion-induced HK-2 cell apoptosis via regulation of the DDIT3/B-cell lymphoma (BCL)-2/caspase-3 signaling pathway. In summary, the results of the present study indicate that miR-96-5p protects HK-2 cells from malathion-induced ER stress-dependent apoptosis by targeting DDIT3.

15.
Biomed Res Int ; 2020: 5914502, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32904518

RESUMO

Background: This systematic review and meta-analysis assessed the role of teriparatide in improving hip fracture healing and function to provide a clinical guide. Methods: The systematic literature review identified randomized controlled trials (RCTs) and controlled studies evaluating teriparatide for elderly hip fractures. A meta-analysis was performed using RevMan version 5.3. Results: This study included two RCTs and four retrospective studies comprising 607 patients, with 269 and 338 patients in the teriparatide and control groups, respectively. The quality of these six studies was moderate. Compared to the control group, teriparatide reduced the time to union (weighted mean difference (WMD) = -1.95; 95% confidence interval (CI): -3.23--0.68; P = 0.003) but did not improve the rate of fracture union at 3 months (odds ratio (OR) = 1.46; 95% CI: 0.50-4.24; P = 0.49) or 6 months (OR = 0.89; 95% CI: 0.44-1.81; P = 0.75). In addition, teriparatide did not decrease the complications, need for reoperation, mortality, rate of deformity after fracture healing, and subsequent fracture or improve hip function. Conclusions: The current limited evidence did not support that teriparatide improves fracture healing in hip fractures, due to study heterogeneity and various sources of biases. Further high-quality, large-sample trials are needed. This trial is registered with PROSPERO with registration number CRD42020152205.

16.
Plast Reconstr Surg ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32868628
17.
Clin Exp Optom ; 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32869355

RESUMO

CLINICAL RELEVANCE: Large-scale data on the association between body stature with biometry parameters and refraction in young adults facilitates an understanding of myopia development. Taller persons have eyes with more negative refractions, longer axial lengths, deeper anterior chambers, flatter corneas, and higher axial length-corneal radius ratio. BACKGROUND: To determine the relationship between body stature with ocular biometry and refraction in young adults. METHODS: This was a cross-sectional university-based study of 16- to 26-year-old students in China. Cycloplegic refraction and corneal curvature were measured using an autorefractor. Ocular parameters, including axial length, anterior chamber depth and lens thickness, were measured using a Lenstar LS900. Data on height and weight were acquired from an annual standardised physical examination and body mass index was calculated. RESULTS: Of 7,971 participants examined in the school clinics, 5,657 (71.0 per cent) were available in the analysis. After adjusting for age, gender, parental myopia, time outdoors, near work and weight, each centimetre of height increase was associated with more negative refraction of -0.023 D, a 0.032 mm increase in axial length, a 0.003 mm increase in anterior chamber depth, a 0.008 mm increase in corneal curvature, and a 0.001 increase in axial length-corneal radius ratio. With regard to weight, a 1 kg heavier person was more likely to have less negative refraction of 0.011 D, a 0.001 mm increase in anterior chamber depth and a 0.002 mm increase in corneal curvature. A similar pattern of significant associations was also found in body mass index. CONCLUSION: Taller, young adults tended to have longer eyes, deeper anterior chambers, flatter corneas, higher axial length-corneal radius ratio, and more negative refraction, adjusted for potential confounders. In contrast, heavier and higher body mass index persons are more hyperopic. The differences in stature may partially explain the variation in refraction and ocular biometric parameters.

18.
Immun Inflamm Dis ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32870597

RESUMO

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and frequently occurring disease of the upper respiratory tract. The nasal instillation of the Gram-negative (G- ) bacterial product lipopolysaccharide (LPS) can induce not only acute sinusitis but also the development of CRSwNP in animal models. Nevertheless, the expression and distribution of LPS in patients with CRSwNP have not been investigated. And the study was to investigate the expression of LPS and its relationship with glucocorticoid receptors (GRs) in CRSwNP. METHODS: Multiple methods, including bacterial culture and immunohistochemistry, were used to detect and analyze nasal bacteria, plasma LPS content, and the levels of LPS and GR-α/ß, cluster of differentiation 68 (CD68), and myeloperoxidase (MPO) expression, as well as their relationship in CRSwNP. RESULTS: The number of G- bacteria and Escherichia coli (E. coli) was not significantly different between CRSwNP subjects and the controls. However, the positive rate of LPS was much higher than that of E. coli in CRSwNP subjects and was significantly higher in noneosinophilic CRSwNP subjects than in eosinophilic CRSwNP subjects. Moreover, the LPS levels were positively correlated with GR-ß but not GR-α expression in CRSwNP. Immunofluorescence assays showed that LPS was mainly detected in CD68+ macrophages and MPO+ neutrophils, in addition to histiocytes, in CRSwNP. CONCLUSIONS: Persistent LPS in CRSwNP can lead to unresolved mucosal inflammation, eventually leading to tissue remodeling and the development of CRSwNP. Our findings suggest that increased LPS content and possible resistance to glucocorticoids may be one of the important pathogenic mechanisms of G- bacteria in CRSwNP.

19.
Sci Rep ; 10(1): 14447, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879359

RESUMO

In this work, we developed a new antibody-targeted and redox-responsive drug delivery system "MSNs-CAIX" by binding the anti-carbonic anhydrase IX antibody (A-CAIX Ab) on the surface of mesoporous silica nanoparticles (MSNs) via disulfide linkages. The design of the composite particles "MSNs-CAIX" involved the synthesis and surface functionalization with thiol groups, 2,2'-dipyridyl disulfide and CAIX antibody. In vitro, CAIX capping the doxorubicin hydrochloric (DOX)-loaded nanoparticles (DOX@MSNs-CAIX) exhibited effectively redox-responsive release in the presence of glutathione (GSH) owing to the cleavage of the disulfide bond. Compared with CAIX negative Mef cells (mouse embryo fibroblast), remarkably more DOX@MSNs-CAIX was internalized into CAIX positive 4T1 cells (mouse breast cancer cells) by receptor-mediation. Tumor targeting in vivo studies clearly demonstrated DOX@MSNs-CAIX accumulated in tumors and induced more tumor cells apoptosis in 4T1 tumor-bearing mice. With great potential, this drug delivery system is a promising candidate for targeted and redox-responsive cancer therapy.

20.
Cancer ; 126(22): 4878-4885, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32940929

RESUMO

BACKGROUND: Postchemotherapy retroperitoneal lymphadenectomy (PC-RPLND) is an essential, yet potentially morbid, therapy for the management of patients with advanced germ cell tumors. In the current study, the authors sought to define the complication profile of PC-RPLND using validated grading systems for intraoperative adverse events (iAEs) and early postoperative complications. METHODS: Between 2000 and 2018, all patients who underwent PC-RPLND were analyzed for iAEs and early postoperative complications using the Kaafarani and Clavien-Dindo classifications, respectively. Logistic regression models were conducted to assess patient and tumor factors associated with iAEs and postoperative complications. RESULTS: Of the 453 patients identified, 115 patients (25%) and 252 patients (56%), respectively, experienced an iAE and postoperative complication. Major iAEs (grade ≥3) were observed in 15 patients (3%) and major postoperative complications (grade ≥3) were noted in 80 patients (18%). The most common iAE was vascular injury (112 of 132 events; 85%), which occurred in 92 patients (20%), and the most frequent postoperative complication was ileus, which occurred in 121 patients (27%). Original and postchemotherapy retroperitoneal mass size, nonretroperitoneal metastases, intermediate and/or poor International Germ Cell Cancer Collaborative Group classification, previous RPLND, elevated tumor markers at the time of RPLND, and anticipated adjuvant surgical procedures increased the risk of both iAEs and postoperative complications. Patients who experienced an iAE were significantly more likely to experience a postoperative complication (odds ratio, 2.50; 95% confidence interval, 1.58-3.97 [P < .001]). CONCLUSIONS: In what to the authors' knowledge is the first analysis of PC-RPLND using validated classifications for both iAEs and postoperative complications, advanced disease and surgical complexity significantly increased the risks of major iAEs and postoperative complications. Standardized reporting of adverse perioperative events allows providers and patients to appreciate the consequences of PC-RPLND during counseling and decision making.

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