Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking,Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling

Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich’s mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich’s solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-β, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.     

微量元素与肿瘤关系的研究进展

本文根据近年国内外的文献报道,概述了微量元素的生理作用及与肿瘤的关系。作者认为肿瘤的发展程度与微量元素含量变化有关,铜／锌比值对恶性肿瘤的疗效和预后估计有一定的参考价值。     

Dilute oral iron solutions as gastrointestinal contrast agents for magnetic resonance imaging; initial clinical experience

Delineation of the gastrointestinal tract in magnetic resonance imaging (MRI) remains a problem. Ferric ammonium citrate is paramagnetic, producing a high MRI signal intensity by virtue of its spin-lattice (T1) relaxation rate enhancement properties. Water is diamagnetic, producing a low MRI signal intensity, especially with short TR and TE times. To compare efficacy for gastrointestinal contrast alteration, ferric ammonium citrate was administered to 18 patients and water was given to 10 patients. Spin-echo imaging at 0.35T was performed after administration of these agents. Ferric ammonium citrate produced high signal intensity within the esophagus, stomach, duodenum, and small intestine that aided in the differentiation of the gastrointestinal tract from adjacent tumors, vessels, and viscera. Delineation of the gut wall was superior using ferric ammonium citrate compared to that produced by water. Delineation of the margins of the pancreas, liver, and kidney from adjacent gastrointestinal tract was also better with ferric ammonium citrate. Optimal distinction between bowel and fat was better with water. Longer TE times (75 to 200 ms) may allow improved contrast between gut and intrabdominal fat using ferric ammonium citrate.     

Efficient System for Delimitation of Benign and Malignant Breast Masses

In this study, a high-performing scheme is introduced to delimit benign and malignant masses in breast ultrasound images. The proposal is built upon by the Nonlocal Means filter for image quality improvement, an Intuitionistic Fuzzy C-Means local clustering algorithm for superpixel generation with high adherence to the edges, and the DBSCAN algorithm for the global clustering of those superpixels in order to delimit masses’ regions. The empirical study was performed using two datasets, both with benign and malignant breast tumors. The quantitative results with respect to the BUSI dataset were JSC≥0.907, DM≥0.913, HD≥7.025, and MCR≤6.431 for benign masses and JSC≥0.897, DM≥0.900, HD≥8.666, and MCR≤8.016 for malignant ones, while the MID dataset resulted in JSC≥0.890, DM≥0.905, HD≥8.370, and MCR≤7.241 along with JSC≥0.881, DM≥0.898, HD≥8.865, and MCR≤7.808 for benign and malignant masses, respectively. These numerical results revealed that our proposal outperformed all the evaluated comparative state-of-the-art methods in mass delimitation. This is confirmed by the visual results since the segmented regions had a better edge delimitation.     

Organic Nanoparticles with Persistent Luminescence for In Vivo Afterglow Imaging-Guided Photodynamic Therapy

Optical imaging-guided photodynamic therapy (PDT), with precise localization and non-invasive treatment of tumors, is an emerging technique with great potential for cancer therapy. However, impaired by tissue auto-fluorescence that causes low signal-to-background ratio (SBR), most fluorescence imaging systems show poor sensitivity to tumors in vivo. In this study, we synthesized organic nanoparticles (ONPs) with persistent luminescence and good biocompatibility for afterglow imaging-guided PDT. The ONPs displayed near-infrared light emission with half-life time at minute level, which offered high SBR and good tissue penetration for in vivo afterglow tumor imaging. Taking advantage of their abundant singlet oxygen generation by NIR laser irradiation guided to the tumor sites, the ONPs also enabled imaging-guided PDT for efficient suppression of tumor growth in mice with minimal damage to major organs.     

A new method of creating minibeam patterns for synchrotron radiation therapy: a feasibility study

Several synchrotrons around the world are currently developing innovative radiotherapy techniques with the aim of palliating and possibly curing human brain tumors. Amongst them, microbeam radiation therapy (MRT) and, more recently, minibeam radiation therapy (MBRT) have shown promising results. In MBRT the beam thickness ranges from 500 to 700 µm with a separation between two adjacent minibeams of the same value, whilst in MRT the thickness is of the order of 25–50 µm with a distance between adjacent microbeams of the order of 200 µm. An original method has been developed and tested at the ESRF ID17 biomedical beamline to produce the minibeam patterns. It utilizes a specially developed high‐energy white‐beam chopper whose action is synchronized with the vertical motion of the target moving at constant speed. Each opening of the chopper generates a horizontal beam print. The method described here has the advantage of being simple and reliable, and it allows for an easy control of the patient safety in future clinical trials. To study the feasibility of the method, dosimetric measurements have been performed using Gafchromic HD‐810 films and compared with Monte Carlo simulations. The results of this comparison are discussed.     

Considerations in applying 3D PRESS H-1 brain MRSI with an eight-channel phased-array coil at 3 T

The purpose of this study was to assess the benefits of a 3 T scanner and an eight-channel phased-array head coil for acquiring three-dimensional PRESS (Point REsolved Spectral Selection) proton (H-1) magnetic resonance spectroscopic imaging (MRSI) data from the brains of volunteers and patients with brain tumors relative to previous studies that used a 1.5 T scanner and a quadrature head coil. Issues that were of concern included differences in chemical shift artifacts, line broadening due to increased susceptibility at higher field strengths, changes in relaxation times and the increased complexity of the postprocessing software due to the need for combining signals from the multichannel data. Simulated and phantom spectra showed that very selective suppression pulses with a thickness of 40 mm and an overpress factor of at least 1.2 are needed to reduce chemical shift artifact and lipid contamination at higher field strengths. Spectral data from a phantom and those from six volunteers demonstrated that the signal-to-noise ratio (SNR) in the eight-channel coil was more than 50% higher than that in the quadrature head coil. For healthy volunteers and eight patients with brain tumors, the SNR at 3 T with the eight-channel coil was on average 1.5 times higher relative to the eight-channel coil at 1.5 T in voxels from normal-appearing brains. In combination with the effect of a higher field strength, the use of the eight-channel coil was able to provide an increase in the SNR of more than 2.33 times the corresponding acquisition at 1.5 T with a quadrature head coil. This is expected to be critical for clinical applications of MRSI in patients with brain tumors because it can be used to either decrease acquisition time or improve spatial resolution.     

Synthetic approaches towards [18F]fluoro-DOG1, a potential radiotracer for the imaging of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) can currently only be identified by invasive biopsy sampling followed by immunohistochemical analysis. It would however be highly advantageous to have a radioligand able to bind the calcium-activated chloride channel DOG1, which is specific for GIST, and thus enable the sensitive, non-invasive and specific functional imaging of the disease by Positron Emission Tomography (PET). For this purpose, we developed different synthetic strategies towards a 4-phenylthiazole-2-amine-based labeling precursor that can be directly reacted with ¹⁸F-fluoride to yield a radiotracer intended to bind DOG1. Of these, a boronic acid pinacol ester radiolabeling precursor could be efficiently reacted with ¹⁸F in a one-step reaction, and the target radioligand [¹⁸F]fluoro-DOG1 be obtained in radiochemical yields of 34.0?±?11.1% within 85?min overall synthesis time.     

Stromal Vascular Fraction Loaded Silk Fibroin Mats Effectively Support the Survival of Diabetic Mice after Pancreatic Islet Transplantation

The aim of this study is to assess whether stromal vascular fraction (SVF)‐soaked silk fibroin nonwoven mats (silk‐SVF) can preserve the functionality of encapsulated pancreatic endocrine cells (alginate‐PECs) after transplantation in the subcutaneous tissue of diabetic mice. Silk scaffolds are selected to create an effective 3D microenvironment for SVF delivery in the subcutaneous tissue before diabetes induction: silk‐SVF is subcutaneously implanted in the dorsal area of five healthy animals; after 15 d, mice are treated with streptozotocin to induce diabetes and then alginate‐PECs are implanted on the silk‐SVF. All animals appear in good health, increasing weight during time, and among them, one presents euglycemia until the end of experiments. On the contrary, when PECs are simultaneously implanted with SVF after diabetes induction, mice are euthanized due to suffering. This work clearly demonstrates that silk‐SVF creates a functional niche in subcutaneous tissue and preserves endocrine cell survival and engraftment.