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Nanotechnology Feb 2019A new type of vapreotide-templated Ag/Au bimetallic nanoshells (Vap@Ag/AuNSs) were successfully designed and fabricated based on polypeptide-directed mineralization and...
A new type of vapreotide-templated Ag/Au bimetallic nanoshells (Vap@Ag/AuNSs) were successfully designed and fabricated based on polypeptide-directed mineralization and hierarchical self-assembly mechanisms under mild synthetic conditions. The nanoparticles with polypeptides serving as a core and coated Ag/Au bimetallic nanoshells exhibit diverse advantages, such as excellent biocompatibility, tumor targeting and low-cost. The Vap@Ag/AuNSs share excellent dispersibility, uniform size (120 nm) and a positive zeta potential (36.74 ± 4.49 mV), hence they easily accumulate in negatively charged tumor tissue. The results of thermal imaging, temperature variation assays and photothermal conversion efficiency (41.6%) indicated that Vap@Ag/AuNSs have excellent photothermal conversion capability. Based on their photothermal response, as well as biocompatibility determined by MTT assay, the prominent anti-tumor effects of Vap@Ag/AuNSs have been verified by fluorescein diacetate staining. Therefore, Vap@Ag/AuNSs are novel and promising candidates for photothermal tumor therapy.
Topics: Antineoplastic Agents; Biocompatible Materials; Gold; Minerals; Nanoshells; Silver; Somatostatin; Temperature
PubMed: 30520422
DOI: 10.1088/1361-6528/aaf0db -
Materials Science & Engineering. C,... Dec 2018Based on the self-assembly properties of vapreotide acetate (Vap), one kind of novel vapreotide acetate‑gold nanoflowers (Vap-AuNFs) was fabricated for the first time...
Based on the self-assembly properties of vapreotide acetate (Vap), one kind of novel vapreotide acetate‑gold nanoflowers (Vap-AuNFs) was fabricated for the first time by biomimetic mineralization method using Vap as a template. The Vap-AuNFs possessed anisotropic structure with a large absorption cross-section, which were face-centered cubic crystalline, exhibiting a remarkable monodisperse, narrow size (154 nm) distribution and good stability in aqueous solution. The apparent anisotropy of the gold nanostructure with high molar extinction coefficient can cause significantly higher plasmon absorption of Vap-AuNFs in the near infrared (NIR) region compared with Au nanoparticles (AuNPs), so the nanocomplex can induce remarkably enhanced photothermal conversion efficiency under NIR light irradiation. Breathtakingly, Vap-AuNFs exhibited superior biocompatibilities compared to AuNPs, as well as enhanced Hela cells lethality under NIR irradiation. This novel method was simple, low cost and green for the design and preparation of anisotropic gold nanoflowers with outstanding NIR laser-induced local hyperthermia, highlighting their potential applications in biomedical fields.
Topics: Gold; HeLa Cells; Humans; Hyperthermia, Induced; Metal Nanoparticles; Neoplasms; Phototherapy; Somatostatin
PubMed: 30274105
DOI: 10.1016/j.msec.2018.08.017 -
Neuropsychopharmacology : Official... Jul 2017Altered brain somatostatin functions recently appeared as key elements for the pathogenesis of stress-related neuropsychiatric disorders. The hippocampus exerts an...
Altered brain somatostatin functions recently appeared as key elements for the pathogenesis of stress-related neuropsychiatric disorders. The hippocampus exerts an inhibitory feedback on stress but the mechanisms involved remain unclear. We investigated herein the role of hippocampal somatostatin receptor subtypes in both stress response and behavioral emotionality using C57BL/6, wild type and sst or sst knockout mice. Inhibitory effects of hippocampal infusions of somatostatin agonists on stress-induced hypothalamo-pituitary-adrenal axis (HPA) activity were tested by monitoring peripheral blood and local hippocampus corticosterone levels, the latter by using microdialysis. Anxiolytic and antidepressant-like effects were determined in the elevated-plus maze, open field, forced swimming, and stress-sensitive beam walking tests. Hippocampal injections of somatostatin analogs and sst or sst but not sst or sst receptor agonists produced rapid and sustained inhibition of HPA axis. sst agonists selectively produced anxiolytic-like behaviors whereas both sst and sst agonists had antidepressant-like effects. Consistent with these findings, high corticosterone levels and anxiety were found in sstKO mice and depressive-like behaviors observed in both sstKO and sstKO strains. Both hippocampal sst and sst receptors selectively inhibit stress-induced HPA axis activation but mediate anxiolytic and antidepressive effects through distinct mechanisms. Such results are to be accounted for in development of pathway-specific somatostatin receptor agents in the treatment of hypercortisolism (Cushing's disease) and stress-related neuropsychiatric disorders.
Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Behavior, Animal; Corticosterone; Emotions; Hippocampus; Hypothalamo-Hypophyseal System; Male; Mice; Mice, Knockout; Octreotide; Pituitary-Adrenal System; Receptors, Somatostatin; Somatostatin; Stress, Psychological
PubMed: 27986975
DOI: 10.1038/npp.2016.281 -
Journal of Clinical Gastroenterology 2017Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort... (Observational Study)
Observational Study
GOALS/BACKGROUND
Data on acute variceal hemorrhage (AVH) in the United States is limited and the best method to stratify risk is not clear. Taking advantage of a prospective US cohort study, we aimed to (1) describe clinical outcomes of AVH and their predictors; (2) compare predictors of 6-week mortality.
STUDY
Prospective 15-center US cohort of patients with cirrhosis presenting with endoscopically proven AVH, all of whom received antibiotics, vapreotide (a somatostain analog) infusion and endoscopic band ligation. Patients were enrolled between August 2006 and April 2008. Primary outcome was 6-week mortality. Secondary outcome was 5-day treatment failure. The prognostic value of Child-Turcotte-Pugh (CTP) class, Model for End-stage Liver Disease (MELD) score and a recent recalibrated MELD were compared.
RESULTS
Seventy eligible patient were enrolled; 18 (26%) patients died within 6-weeks of index bleed. Demographic, clinical, and laboratory data were compared between survivors and nonsurvivors. Multivariate models showed that admission CTP or the MELD score (separately) were independent predictors of survival. The discriminative values of CTP (area under receiver operating characteristic: 0.75) and MELD (area under receiver operating characteristic: 0.79) were good and not significantly different (P=0.27). However, calibration (correlation between observed and predicted mortality) test was significantly better for CTP than for MELD, with the recently described recalibrated MELD model having the worst agreement. Predicted mortality for CTP-A was <10%, CTP-B 10% to 30%; and CTP-C >33%.
CONCLUSIONS
AVH mortality of 26% in the United States is in the upper range limit compared with recent series but may be due to inclusion of patients with more advanced cirrhosis. CTP score has the best overall performance in the prediction of 6-week mortality and is best at stratifying risk.
Topics: Decision Support Techniques; Disease Progression; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Risk Factors; Time Factors; Treatment Failure; United States
PubMed: 27779613
DOI: 10.1097/MCG.0000000000000733 -
Oncotarget Apr 2016Malignant brain glioma is the most lethal and aggressive type of cancer. Surgery and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood-brain barrier...
Malignant brain glioma is the most lethal and aggressive type of cancer. Surgery and radiotherapy cannot eliminate all glioma stem cells (GSCs) and blood-brain barrier (BBB) restricts the movement of antitumor drugs from blood to brain, thus leading to the poor prognosis with high recurrence rate. In the present study, the targeting conjugates of cholesterol polyethylene glycol polyethylenimine (CHOL-PEG2000-PEI) and D-a-tocopheryl polyethylene glycol 1000 succinate vapreotide (TPGS1000-VAP) were newly synthesized for transporting drugs across the BBB and targeting glioma cells and GSCs. The multifunctional targeting vinorelbine plus tetrandrine liposomes were constructed by modifying the targeting conjugates. The studies were undertaken on BBB model, glioma cells, GSCs, and glioma-bearing mice. In vitro results showed that multifunctional targeting drugs-loaded liposomes with suitable physicochemical property could enhance the transport drugs across the BBB, increase the intracellular uptake, inhibit glioma cells and GSCs, penetrate and destruct the GSCs spheroids, and induce apoptosis via activating related apoptotic proteins. In vivo results demonstrated that multifunctional targeting drugs-loaded liposomes could significantly accumulate into brain tumor location, show the specificity to tumor sites, and result in a robust overall antitumor efficacy in glioma-bearing mice. These data suggested that the multifunctional targeting vinorelbine plus tetrandrine liposomes could offer a promising strategy for treating brain glioma.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzylisoquinolines; Brain Neoplasms; Cell Line, Tumor; Glioma; Liposomes; Mice; Mice, Inbred ICR; Molecular Targeted Therapy; Neoplastic Stem Cells; Random Allocation; Vinblastine; Vinorelbine
PubMed: 27029055
DOI: 10.18632/oncotarget.8360