Phase I Clinical Evaluation of Designed Ankyrin Repeat Protein [Tc]Tc(CO)-(HE)-Ec1 for Visualization of EpCAM-Expressing Lung Cancer.

A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using Tc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection.

Human and animal intestinal commensals and probiotics vs modern challenges of biosafety: problems and prospects.

The appearance of an array of data on the study of the intestinal microbiota in Metazoa has significantly expanded our understanding of the role of commensals in the control of a wide range of physiological functions in higher organisms in norm and pathology. In the intestine, where the microbial load significantly exceeds the number of microorganisms of other ecosystems, the components of the intestinal microbiota are a constant source of stimuli that induce activation of the host immune system. The introduction into practice of biomedical research of innovative high-resolution methods, including   multi-omics technologies, has brought data that change our understanding of intestinal commensals, including probiotics with GRAS status, widely used in medicine, agriculture and biotechnology.

Evaluation of HER2/neu Expression in Metastatic Axillary Lymph Node Tissue of Breast Cancer Patients Using [99mTc]Tc-(HE)3-G3.

Anatomic visualization and molecular typing of metastatic regional lymph nodes in breast cancer patients are a serious clinical challenge in modern oncology. According to the results of previous studies, [99mTc]Tc-(HE)3-G3 has proven to be a promising diagnostic agent in differentiating the HER2/neu receptor status in primary breast tumors ( < 0.05, Mann-Whitney test).

Decellularized Umbilical Cord as a Scaffold to Support Healing of Full-Thickness Wounds.

The umbilical cord is a material that enhances regeneration and is devoid of age-related changes in the extracellular matrix (ECM). The aim of this work was to develop a biodegradable scaffold from a decellularized human umbilical cord (UC-scaffold) to heal full-thickness wounds. Decellularization was performed with 0.

Evaluation of Approaches for the Assessment of HER2 Expression in Breast Cancer by Radionuclide Imaging Using the Scaffold Protein [Tc]Tc-ADAPT6.

Due to its small size and high affinity binding, the engineered scaffold protein ADAPT6 is a promising targeting probe for radionuclide imaging of human epidermal growth factor receptor type 2 (HER2). In a Phase I clinical trial, [Tc]Tc-ADAPT6 demonstrated safety, tolerability and capacity to visualize HER2 expression in primary breast cancer. In this study, we aimed to select the optimal parameters for distinguishing between breast cancers with high and low expression of HER2 using [Tc]Tc-ADAPT6 in a planned Phase II study.

Humic Polyelectrolytes Facilitate Rapid Microwave Synthesis of Silver Nanoparticles Suitable for Wound-Healing Applications.

This article describes the one-pot microwave synthesis of silver nanoparticles (AgNPs) assisted with natural polyelectrolytes-humic substances (HS). The humic polyelectrolytes served both as chemical reductants for silver ions and as end-capping agents for AgNPs. Three commercially available sodium humates extracted from lignites and leonardite and one sodium fulvate isolated from natural brown water seeped through peat deposits were used in this study.

Phase I clinical evaluation of Tc-labeled Affibody molecule for imaging HER2 expression in breast cancer.

The determination of tumor human epidermal growth factor receptor type 2 (HER2) status is of increasing importance with the recent approval of more efficacious HER2-targeted treatments. There is a lack of suitable methods for clinical HER2 expression assessment. Affibody molecules are small affinity proteins ideal for imaging detection of receptors, which are engineered using a small (molecular weight 6.

Direct Intra-Patient Comparison of Scaffold Protein-Based Tracers, [Tc]Tc-ADAPT6 and [Tc]Tc-(HE)-G3, for Imaging of HER2-Positive Breast Cancer.

Previous Phase I clinical evaluations of the radiolabelled scaffold proteins [Tc]Tc-ADAPT6 and DARPin [Tc]Tc-(HE)-G3 in breast cancer patients have demonstrated their safety and indicated their capability to discriminate between HER2-positive and HER2-negative tumours. The objective of this study was to compare the imaging of HER2-positive tumours in the same patients using [Tc]Tc-ADAPT6 and [Tc]Tc-(HE)-G3. Eleven treatment-naïve female patients (26-65 years) with HER2-positive primary and metastatic breast cancer were included in the study.

The GRPR Antagonist [Tc]Tc-maSSS-PEG-RM26 towards Phase I Clinical Trial: Kit Preparation, Characterization and Toxicity.

Gastrin-releasing peptide receptors (GRPRs) are overexpressed in the majority of primary prostate tumors and in prostatic lymph node and bone metastases. Several GRPR antagonists were developed for SPECT and PET imaging of prostate cancer. We previously reported a preclinical evaluation of the GRPR antagonist [Tc]Tc-maSSS-PEG-RM26 (based on [D-Phe, Sta, Leu-NH]BBN(6-14)) which bound to GRPR with high affinity and had a favorable biodistribution profile in tumor-bearing animal models.

Increasing the Thermal Stability and High-Temperature Strength of Vanadium Alloys by Strengthening with Nanosized Non-Metallic Particles.

Using the methods of scanning and transmission electron microscopy, the features of the structural-phase state of a vanadium alloy of the V-Cr-Ta-Zr system after a combined treatment, which consisted in cyclic alternation of thermomechanical and chemical-heat treatments, were studied. The values of yield strength and ductility of the V-Cr-Ta-Zr alloy were determined, depending on the stabilization and test temperatures. It was established that, after the combined treatment, the structural-phase state of the V-Cr-Ta-Zr alloy was composite, in which the joint implementation of dispersion and substructural strengthening ensured the formation of a gradient grain structure with a polygonal state, the elements of which were fixed by nanosized ZrO particles characterized by a high thermal stability.

Phase I Trial of [Tc]Tc-maSSS-PEG-RM26, a Bombesin Analogue Antagonistic to Gastrin-Releasing Peptide Receptors (GRPRs), for SPECT Imaging of GRPR Expression in Malignant Tumors.

The gastrin-releasing peptide receptor (GRPR) is overexpressed in prostate cancer (PCa) and in hormone-driven breast cancer (BCa). The aim of this phase I clinical trial was to evaluate safety, biodistribution, and dosimetry after the administration of the recently developed GRPR-targeting antagonistic bombesin analogue [Tc]Tc-maSSS-PEG-RM26 in PCa and BCa patients. Planar and whole-body SPECT/CT imaging was performed in six PCa patients and seven BCa patients 2, 4, 6, and 24 h post the intravenous administration of 40 µg of [Tc]Tc-maSSS-PEG-RM26 (600-700 MBq).

A concept of "materials" diffraction and imaging beamline for SKIF: Siberian circular photon source.

Over the next decade, the extremely brilliant fourth generation synchrotron radiation sources are set to become a key driving force in materials characterization and technology development. In this study, we present a conceptual design of a versatile "Materia" diffraction and imaging beamline for a low-emittance synchrotron radiation facility. The beamline was optimized for operation with three main principal delivery regimes: parallel collimated beam ∼1 mm beam size, micro-focus regime with ∼10 μm beam spot size on the sample, and nano-focus regime with <100 nm focus.

Performing a radical trachelectomy with uterine transposition in a patient with stage IB2 cervical cancer: A case report.

We describe a case of a woman with invasive IB2 cervical cancer who desired to maintain fertility and required complex treatment. The suggested surgical approach with uterine transposition improves the existing radical trachelectomy procedure. Oncologic outcomes are encouraging, and no perioperative complications were noted.

The Evolution of Targeted Radionuclide Diagnosis of HER2-Positive Breast Cancer.

This review examines the evolution of the radionuclide diagnosis of HER2-positive breast cancer using various compounds as a targeting module in clinical practice: from full-length antibodies to a new group of small synthetic proteins called alternative scaffold proteins. This topic is of especial relevance today in view of the problems attendant to the detection of breast cancer with HER2/neu overexpression, which, in most cases, introduce errors in the treatment of patients. The results of clinical studies of radiopharmaceuticals based on affibody molecules, ADAPTs, and DARPins for SPECT and PET have demonstrated good tolerability of the compounds, their rapid excretion from the body, and the possibility to differentiate tumor sites depending on the HER2/neu status.

Phase I Clinical Trial Using [Tc]Tc-1-thio-D-glucose for Diagnosis of Lymphoma Patients.

Similar to [F]-FDG, [Tc]Tc-1-thio-D-glucose ([Tc]Tc-TG) also binds to GLUT receptors. The aim of this Phase I study was to evaluate the safety, biodistribution and dosimetry of [Tc]Tc-TG. Twelve lymphoma patients were injected with 729 ± 102 MBq [Tc]Tc-TG.

Development of Resistance to Clarithromycin and Amoxicillin-Clavulanic Acid in Is Followed by Genomic Rearrangements and Evolution of Virulence.

Ensuring the safety of the use of probiotics is a top priority. Obviously, in addition to studying the beneficial properties of lactic acid bacteria, considerable attention should be directed to assessing the virulence of microorganisms as well as investigating the possibility of its evolution under conditions of selective pressure. To assess the virulence of probiotics, it is now recommended to analyze the genomes of bacteria in relation to the profiles of the virulome, resistome, and mobilome as well as the analysis of phenotypic resistance and virulence .

Extracellular Vesicles from Mycoplasmas Can Penetrate Eukaryotic Cells In Vitro and Modulate the Cellular Proteome.

The extracellular vesicles (EVs) produced by bacteria transport a wide range of compounds, including proteins, DNA and RNA, mediate intercellular interactions, and may be important participants in the mechanisms underlying the persistence of infectious agents. This study focuses on testing the hypothesis that the EVs of mycoplasmas, the smallest prokaryotes capable of independent reproduction, combined in the class referred to as Mollicutes, can penetrate into eukaryotic cells and modulate their immunoreactivity. To verify this hypothesis, for the first time, studies of in vitro interaction between human skin fibroblasts and vesicles isolated from Acholeplasma laidlawii (the ubiquitous mycoplasma that infects higher eukaryotes and is the main contaminant of cell cultures and vaccines) were conducted using confocal laser scanning microscopy and proteome profiling, employing a combination of 2D-DIGE and MALDI-TOF/TOF, the Mascot mass-spectrum analysis software and the DAVID functional annotation tool.

Adaptation to Antimicrobials and Pathogenicity in Mycoplasmas: Development of Ciprofloxacin-Resistance and Evolution of Virulence in Acholeplasma laidlawii.

For the first time it was shown that the development of resistance to ciprofloxacin in vitro in Acholeplasma laidlawii, a mycoplasma which is widely spread in nature and which is the main contaminant of cell cultures and vaccines, is associated with diverse pathways of virulence evolution: virulome and virulence differ significantly between ciprofloxacin-resistant strains, including those with the same level of antimicrobial resistance.

Phase I Trial of Tc-(HE)-G3, a DARPin-Based Probe for Imaging of HER2 Expression in Breast Cancer.

Radionuclide molecular imaging of human epidermal growth factor receptor type 2 (HER2) expression may enable a noninvasive discrimination between HER2-positive and HER2-negative breast cancers for stratification of patients for HER2-targeted treatments. DARPin (designed ankyrin repeat proteins) G3 is a small (molecular weight, 14 kDa) scaffold protein with picomolar affinity to HER2. The aim of this first-in-humans study was to evaluate the safety, biodistribution, and dosimetry of Tc-(HE)-G3.

Quantification of the radiosensitization effect of high-nanoparticles on photon irradiated cells: combining Monte Carlo simulations and an analytical approach to the local effect model.

experiments show significant reduction in the survival fraction of cells under irradiation treatments assisted with high-nanoparticles (NPs). In order to predict the radiosensitization effect of NPs, a modification of the local effect model (LEM), in which the energy deposition from NPs is assessed by Monte Carlo (MC) radiation transport codes, has been employed in the past. In this work, a combined framework that splits the consideration of the radiosensitization effect into two steps is proposed.

Preclinical Evaluation of Tc-ZHER2:41071, a Second-Generation Affibody-Based HER2-Visualizing Imaging Probe with a Low Renal Uptake.

Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [Tc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface.

Vibrational spectra of La@C and Ce@C endohedral fullerenes: Influence of spin state multiplicity.

Endohedral fullerenes with paramagnetic encapsulated atoms are new magnetic materials of interest for numerous applications from medicine to quantum computers. An important phenomenon with endohedral fullerenes is the appearance of new vibrational frequencies not associated with empty fullerenes. The vibrational spectra of the lanthanide endohedral fullerenes La@C and Ce@C in various spin states are calculated using the density functional method.

Preclinical Evaluation of Tc-Labeled GRPR Antagonists maSSS/SES-PEG-RM26 for Imaging of Prostate Cancer.

Background: Gastrin-releasing peptide receptor (GRPR) is an important target for imaging of prostate cancer. The wide availability of single-photon emission computed tomography/computed tomography (SPECT/CT) and the generator-produced Tc can be utilized to facilitate the use of GRPR-targeting radiotracers for diagnostics of prostate cancers.

Methods: Synthetically produced mercaptoacetyl-Ser-Ser-Ser (maSSS)-PEG-RM26 and mercaptoacetyl-Ser-Glu-Ser (maSES)-PEG-RM26 (RM26 = d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH) were radiolabeled with Tc and characterized in vitro using PC-3 cells and in vivo, using NMRI or PC-3 tumor bearing mice.

Adaptation of Mycoplasmas to Antimicrobial Peptides: Development of Melittin Resistance in Acholeplasma laidlawii Is Associated with Changes in Genomic and Proteomic Profiles and in Virulence.

For the first time it is shown that the development of resistance to melittin in Acholeplasma laidlawii, a mycoplasma that is widely spread in nature and that is the main contaminant of cell cultures and vaccines, is associated with significant changes in the genomic profile, in cellular and vesicular proteomes, as well as in virulence.