The Prognosis of Anti-Angiogenesis Treatments Combined with Standard Therapy for Newly Diagnosed Glioblastoma: A Meta-Analysis of Randomized Controlled Trials

Background and Purpose: Although bevacizumab (BV) has been approved as second-line therapy for recurrent glioblastoma (GB), the efficacy and safety of BV for patients with newly diagnosed GB remain unclear. Methodology/Principal Findings: We systematically searched electronic databases (PubMed, EMBASE, OVID, etc.) to identify related studies published from January 1966 and August 2016. Eight randomized controlled trials including a total of 2,185 patients with GB were included. We found that the median progression-free survival (PFS) was higher in the BV group than in the standard therapy (ST) group (pooled hazard ratio, 0.73;95% CI, 0.62-0.86;P = 0.0001). Compared with ST, BV improved the PFS rate at 6 months (OR 3.33, 95% CI 2.73-4.06, p<0.00001) and 12 months (OR 2.10, 95% CI 1.74-2.54, p< 0.00001). There were no significant differences in median overall survival between the BV and ST groups (OR, 1.01;95% CI, 0.83-1.23;P = 0.95). The BV group had higher survival rates at 6 months (OR, 1.41;95% CI, 1.09-1.84;P = 0.01) and 12 months (OR, 1.23;95% CI, 1.02-1.48;P = 0.03), but a low survival rate at the 36-month follow-up (OR, 0.57;95% CI, 0.32-0.98;P = 0.04). For the incidence of adverse events, three adverse outcomes were found to be significantly different between BV and ST groups, including hypertension (8.37% vs. 1.62%, p<0.000001), proteinuria (7.65% vs. 0%, p<0.001), and fatigue (14.54% vs. 9.01%, p = 0.05). Conclusions/Significance: Our study indicates that combination of BV with ST for newly diagnosed GB did not improve the median overall survival but result in longer median PFS, maintaining the quality of life and functional status. However, the long-term use of BV is associated with a higher incidence of adverse events and mortality

Polydopamine-based loaded temozolomide nanoparticles conjugated by peptide-1 for glioblastoma chemotherapy and photothermal therapy

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM).Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice.Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p &lt; 0.05).Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM

Dual Optical Frequency Comb Neuron: Co‐Developing Hardware and Algorithm

Previous studies on photonic neural network have demonstrated that algorithm can inspire hardware design. This study seeks to demonstrate that hardware can also inspire algorithm design. To further exploit the advantages of photonic analog computing, the authors develop hardware and algorithm simultaneously for photonic convolutional neural networks. Specifically, this work developed an architecture called dual optical frequency comb neuron (DOFCN) enabled by an integrated microcomb to perform cosinusoidal nonlinear activation and vector convolution without temporal or spatial dispersion and large‐scale modulator arrays. Furthermore, DOFCN‐based composite vector convolutional neural networks (CVCNNs), an optical‐electric hybrid model, are proposed to perform classification and regression tests in signal modulation format identification and optical structure inverse design tasks, respectively. The ablation experiments show that under 4‐bit precision limit, the element‐wise activation CVCNN has 14% higher classification accuracy, 76% lower regression residuals, and 100% higher training efficiency than that of the 32‐bit standard convolutional neural network (CNN). DOFCN exhibits impressive spectral information processing ability to facilitate signal‐processing tasks related to optics and electromagnetics

The PRISMA flow chart of the meta-analysis.

<p>The PRISMA flow chart of the meta-analysis.</p

The funnel plot of OS on patients with newly diagnosed GB.

<p>The funnel plot of OS on patients with newly diagnosed GB.</p

The pooled HR of median PFS comparing BV with ST in patients with GB.

<p>The pooled HR of median PFS comparing BV with ST in patients with GB.</p

Image3_Polydopamine-based loaded temozolomide nanoparticles conjugated by peptide-1 for glioblastoma chemotherapy and photothermal therapy.TIF

Purpose: Nanoparticles (NPs) of the polydopamine (PDA)-based,loaded with temozolomide (TMZ) and conjugated with Pep-1 (Peptide-1) as a feasible nano-drug delivery system were constructed and utilized for chemotherapy (CT) and photothermal therapy (PTT) of glioblastoma (GBM).Method: PDA NPs were synthesized from dopamine (DA) hydrochloride and reacted with TMZ to obtain the PDA-TMZ NPs and then the PDA NPs and the PDA-TMZ NPs were conjugated and modified by Pep-1 to obtain the Pep-1@PDA NPs and Pep-1@PDA-TMZ NPs via the Schiff base reaction (SBR), respectively.Their dimensions, charge, and shape were characterized by dynamic light scattering (DLS) and scanning electron microscope (SEM). The assembly of TMZ was verified by Fourier-transform infrared spectroscopy (FT-IR) and ultraviolet and visible spectroscopy (UV-Vis). The biostability of both the nanocarrier and the synthetic NPs were validated using water and fetal bovine serum (FBS). The antitumor activities of the PDA-TMZ NPs and Pep-1@PDA-TMZ NPs were verified in U87 cells and tumor-bearing nude mice.Results: The prepared PDA NPs, PDA-TMZ NPs, Pep-1@PDA NPs, and Pep-1@PDA-TMZ NPs were regular and spherical, with dimension of approximately 122, 131, 136, and 140 nm, respectively. The synthetic nanoparticles possessed good dispersity, stability,solubility, and biocompatibility. No obvious toxic side effects were observed, and the loading rate of TMZ was approximately 50%.In vitro research indicated that the inhibition ratio of the Pep-1@PDA-TMZ NPs combined with 808 nm laser was approximately 94% for U87 cells and in vivo research was approximately 77.13%, which was higher than the ratio of the other groups (p Conclusion: Pep-1 was conjugated and modified to PDA-TMZ NPs, which can serve as a new targeted drug nano-delivery system and can offer a CT and PTT integration therapy against GBM. Thus, Pep-1@PDA-TMZ NPs could be a feasible approach for efficient GBM therapy, and further provide some evidence and data for clinical transformation so that gradually conquer GBM.</p