Publications by authors named "Sergey Kuznetsov"

80 Publications

T-cell immunoglobulin and ITIM domain, as a potential immune checkpoint target for immunotherapy of colorectal cancer.

IUBMB Life 2021 May 30;73(5):726-738. Epub 2021 Mar 30.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

The importance of the tumor microenvironment in cancer progression has been well studied for many years. Immune checkpoint inhibitors (ICIs) are regarded as potential strategies in enhancing the immune responses in patients with cancer, particularly colorectal cancer (CRC). Notably, CRCs are extraordinarily heterogeneous and mostly are microsatellite-stable (MSS) or cold tumors, which means that the immune response is not usually as strong as that of foreign cells. T-cell immunoglobulin and ITIM domain (TIGIT) is a new immune checkpoint receptor overexpressed inside the CRC tumor-immune microenvironments. Moreover, several studies have shown that TIGIT in combination with other ICIs and/or conventional treatments, can lead to a robust anti-tumor response in CRC. This review looks deep inside TIGIT expression patterns, their various functions, and possible immunotherapy strategies to increase survival rates and decrease immune-related adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/iub.2461DOI Listing
May 2021

3D Mueller matrix mapping of layered distributions of depolarisation degree for analysis of prostate adenoma and carcinoma diffuse tissues.

Sci Rep 2021 Mar 4;11(1):5162. Epub 2021 Mar 4.

Optoelectronics and Measurement Techniques Laboratory, University of Oulu, 90014, Oulu, Finland.

Prostate cancer is the second most common cancer globally in men, and in some countries is now the most diagnosed form of cancer. It is necessary to differentiate between benign and malignant prostate conditions to give accurate diagnoses. We aim to demonstrate the use of a 3D Mueller matrix method to allow quick and easy clinical differentiation between prostate adenoma and carcinoma tissues with different grades and Gleason scores. Histological sections of benign and malignant prostate tumours, obtained by radical prostatectomy, were investigated. We map the degree of depolarisation in the different prostate tumour tissues using a Mueller matrix polarimeter set-up, based on the superposition of a reference laser beam with the interference pattern of the sample in the image plane. The depolarisation distributions can be directly related to the morphology of the biological tissues. The dependences of the magnitude of the 1st to 4th order statistical moments of the depolarisation distribution are determined, which characterise the distributions of the depolarisation values. To determine the diagnostic potential of the method three groups of histological sections of prostate tumour biopsies were formed. The first group contained 36 adenoma tissue samples, while the second contained 36 carcinoma tissue samples of a high grade (grade 4: poorly differentiated-4 + 4 Gleason score), and the third group contained 36 carcinoma tissue samples of a low grade (grade 1: moderately differentiated-3 + 3 Gleason score). Using the calculated values of the statistical moments, tumour tissues are categorised as either adenoma or carcinoma. A high level (> 90%) accuracy of differentiation between adenoma and carcinoma samples was achieved for each group. Differentiation between the high-grade and low-grade carcinoma samples was achieved with an accuracy of 87.5%. The results demonstrate that Mueller matrix mapping of the depolarisation distribution of prostate tumour tissues can accurately differentiate between adenoma and carcinoma, and between different grades of carcinoma. This represents a first step towards the implementation of 3D Mueller matrix mapping for clinical analysis and diagnosis of prostate tumours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-83986-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933337PMC
March 2021

Magnetic phase transition and lattice dynamic features in ErBC borocarbide.

J Phys Condens Matter 2021 Feb 16. Epub 2021 Feb 16.

Ames Laboratory, Ames, Iowa 50011, USA, Ames, Iowa, 50011, UNITED STATES.

A sample of erbium borocarbide ErB2C was synthesized from a stoichiometric mixture of erbium, boron, and pyrographite hydride. Temperature dependent magnetic susceptibility, heat capacity and lattice parameters of borocarbide at 2 - 300 K were experimentally investigated, the Raman spectrum was determined and analyzed. Sharp anomalies in the heat capacity and magnetic properties of ErB2C near T = 16.3 K, caused by the transition to the antiferromagnetic state, as well as diffuse anomalies at a higher temperature, caused by the effect of the crystal field (Schottky anomalies) were revealed. It was found that the magnetic phase transition does not cause measurable anomalies in the lattice parameters of borocarbide due to the weak coupling between the Er3+ ion subsystem and the B-C layers. Almost zero thermal expansion of erbium borocarbide in the basal plane (along a and b axes) (anisotropic Invar effect) as well as an unusual character of the c - axis thermal expansion were observed. The first of these features is due to the high bonding energy in the B-C layers and the weak bond between the layers in the borocarbide crystal lattice. It was found that the anomalous expansion along the c axis is a consequence of the action of the crystal field. The splitting scheme for the ground level of Er3+ ions by crystal field was determined from the analysis of the Schottky anomaly of the heat capacity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-648X/abe6deDOI Listing
February 2021

Raman spectroscopic detection of polyene-length distribution for high-sensitivity monitoring of photo- and thermal degradation of polyvinylchloride.

Spectrochim Acta A Mol Biomol Spectrosc 2021 May 22;252:119494. Epub 2021 Jan 22.

Physics and Earth Sciences, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany. Electronic address:

The degradation of the ubiquitous polyvinylchloride (PVC) material under the influence of various factors is known to result commonly in polyene formation. Such polyene defects occur in the form of conjugated aliphatic chains with different lengths and contents, and their sensitive and length-specific monitoring is important for the assessment of PVC degradation. Here, we report on the resonance-enhanced Raman signatures of polyene sequences of varying lengths in photo- and thermally degraded PVC films. The lengths of polyene segments have been estimated based on their selectively enhanced and spectrally resolved contributions to the Raman bands assigned to the stretching vibrations of conjugated double carbon bonds. Using deconvolution analysis of a characteristic Raman band of polyenes, we especially demonstrate that the spectral signatures of polyene segments corresponding to other various electronic resonances contribute to the Raman spectral envelope observed at a given resonant excitation. In most cases, we observe an asymmetric band profile, indicating an asymmetric length distribution of polyene defects formed in PVC films upon a mild degradation extent less than 1% mass loss. We also demonstrate that the wavenumber (ν) of the stretching vibrations of single carbon bonds in the polyene sequences of degraded PVC is inversely related to the number (n) of double carbon bonds by an empirical equation n=476·cm/ν-1082·cm. To the best of our knowledge, while considering different laser excitations spanning the range of possible electronic resonances from blue to near-infrared for Raman investigations, the present work includes (i) the first Raman spectral deconvolution study for the 532.0 nm excitation wavelength used in most portable Raman probes nowadays and (ii) the screening of polyene defects also beyond the red edge of the visible spectrum and the evidence of a resonance-enhanced polyene signal at 647.1 nm. Important new information has been obtained about polyene lengths and spectral distribution for PVC, whose critical physical properties ranging from flexibility to electrical resistance are severely affected by polyene formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.saa.2021.119494DOI Listing
May 2021

Multiphoton tomography in differentiation of morphological and molecular subtypes of breast cancer: A quantitative analysis.

J Biophotonics 2021 Feb 1:e202000471. Epub 2021 Feb 1.

Privolzhsky Research Medical University, Nizhny Novgorod, Russia.

In this study multiphoton tomography, based on second harmonic generation (SHG), and two-photon-excited fluorescence (TPEF) was used to visualize both the extracellular matrix and tumor cells in different morphological and molecular subtypes of human breast cancer. It was shown, that quantified assessment of the SHG based imaging data has great potential to reveal differences of collagen quantity, organization and uniformity in both low- and highly- aggressive invasive breast cancers. The values of quantity and uniformity of the collagen fibers distribution were significantly higher in low-aggressive breast cancer compared to the highly-aggressive subtypes, while the value representing collagen organization was lower in the former type. Additionally, it was shown, that TPEF detection of elastin fibers and amyloid protein may be used as a biomarker of detection the low-aggressive breast cancer subtype. Thus, TPEF/SHG imaging offers the possibility of becoming a useful tool for the rapid diagnosis of various subtypes of breast cancer during biopsy as well as for the intraoperative determinination of tumor-positive resection margins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbio.202000471DOI Listing
February 2021

Route to hyperbolic hyperchaos in a nonautonomous time-delay system.

Chaos 2020 Nov;30(11):113113

Kotel'nikov's Institute of Radio-Engineering and Electronics of RAS, Saratov Branch, Zelenaya 38, Saratov 410019, Russia.

We consider a self-oscillator whose excitation parameter is varied. The frequency of the variation is much smaller than the natural frequency of the oscillator so that oscillations in the system are periodically excited and decayed. Also, a time delay is added such that when the oscillations start to grow at a new excitation stage, they are influenced via the delay line by the oscillations at the penultimate excitation stage. Due to nonlinearity, the seeding from the past arrives with a doubled phase so that the oscillation phase changes from stage to stage according to the chaotic Bernoulli-type map. As a result, the system operates as two coupled hyperbolic chaotic subsystems. Varying the relation between the delay time and the excitation period, we found a coupling strength between these subsystems as well as intensity of the phase doubling mechanism responsible for the hyperbolicity. Due to this, a transition from non-hyperbolic to hyperbolic hyperchaos occurs. The following steps of the transition scenario are revealed and analyzed: (a) an intermittency as an alternation of long staying near a fixed point at the origin and short chaotic bursts; (b) chaotic oscillations with frequent visits to the fixed point; (c) plain hyperchaos without hyperbolicity after termination visiting the fixed point; and (d) transformation of hyperchaos to the hyperbolic form.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1063/5.0022645DOI Listing
November 2020

Diagnostic Accuracy of Cross-Polarization OCT and OCT-Elastography for Differentiation of Breast Cancer Subtypes: Comparative Study.

Diagnostics (Basel) 2020 Nov 24;10(12). Epub 2020 Nov 24.

Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603950 Nizhny Novgorod, Russia.

The possibility to assess molecular-biological and morphological features of particular breast cancer types can improve the precision of resection margin detection and enable accurate determining of the tumor aggressiveness, which is important for treatment selection. To enable reliable differentiation of breast-cancer subtypes and evaluation of resection margin, without performing conventional histological procedures, here we apply cross-polarization optical coherence tomography (CP-OCT) and compare it with a novel variant of compressional optical coherence elastography (C-OCE) in terms of the diagnostic accuracy (Ac) with histological verification. The study used 70 excised breast cancer specimens with different morphological structure and molecular status (Luminal A, Luminal B, Her2/Neo+, non-luminal and triple-negative cancer). Our first aim was to formulate convenient criteria of visual assessment of CP-OCT and C-OCE images intended (i) to differentiate tumorous and non-tumorous tissues and (ii) to enable more precise differentiation among different malignant states. We identified such criteria based on the presence of heterogeneities and characteristics of signal attenuation in CP-OCT images, as well as the presence of inclusions/mosaic structures combined with visually feasible assessment of several stiffness grades in C-OCE images. Secondly, we performed a blinded reader study of the Ac of C-OCE versus CP-OCT, for delineation of tumorous versus non-tumorous tissues followed by identification of breast cancer subtypes. For tumor detection, C-OCE showed higher specificity than CP-OCT (97.5% versus 93.3%) and higher Ac (96.0 versus 92.4%). For the first time, the Ac of C-OCE and CP-OCT were evaluated for differentiation between non-invasive and invasive breast cancer (90.4% and 82.5%, respectively). Furthermore, for invasive cancers, the difference between invasive but low-aggressive and highly-aggressive subtypes can be detected. For differentiation between non-tumorous tissue and low-aggressive breast-cancer subtypes, Ac was 95.7% for C-OCE and 88.1% for CP-OCT. For differentiation between non-tumorous tissue and highly-aggressive breast cancers, Ac was found to be 98.3% for C-OCE and 97.2% for CP-OCT. In all cases C-OCE showed better diagnostic parameters independently of the tumor type. These findings confirm the high potential of OCT-based examinations for rapid and accurate diagnostics during breast conservation surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics10120994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760404PMC
November 2020

Hydrophobic up-conversion carboxylated nanocellulose/fluoride phosphor composite films modified with alkyl ketene dimer.

Carbohydr Polym 2020 Dec 8;250:116866. Epub 2020 Aug 8.

Kurnakov Institute of General and Inorganic Chemistry of the Russian Academy of Sciences, 31 Leninsky Pr., Moscow 119991, Russia. Electronic address:

Hydrophobic up-conversion nanocomposite films have been developed based on TEMPO-oxidized cellulose nanofibrils (TOCNF) modified with alkyl ketene dimer (AKD) as a matrix and MF:Ho (M = Ca, Sr) as a phosphor. Fabrication of homogeneous, strong and translucent TOCNF/MF:Ho-AKD films with water contact angle of 123 ± 2° was accomplished with mild drying at 110 °C. These hydrophobic nanocomposite films demonstrated stable up-conversion luminescence in the visible spectral range upon excitation of the I level of Ho ions by laser irradiation at 1912 nm both under ambient conditions and in a humid atmosphere (92 ± 2% humidity). The absence of luminescence quenching in a high humidity atmosphere for TOCNF/MF:Ho-AKD composite films was considered to be due to the reliable shielding effect of the hydrophobic TOCNF-AKD matrix. The films show promise for visualizing 2 μm laser radiation in medicine and monitoring of the atmosphere.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.carbpol.2020.116866DOI Listing
December 2020

Raman Spectroscopy Study of Structurally Uniform Hydrogenated Oligomers of α-Olefins.

Polymers (Basel) 2020 Sep 21;12(9). Epub 2020 Sep 21.

Department of Chemistry, M.V. Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia.

The expansion of the range of physico-chemical methods in the study of industrially significant α-olefin oligomers and polymers is of particular interest. In our article, we present a comparative Raman study of structurally uniform hydrogenated dimers, trimers, tetramers, and pentamers of 1-hexene and 1-octene, that are attractive as bases for freeze-resistant engine oils and lubricants. We found out that the joint monitoring of the disorder longitudinal acoustic mode (D-LAM) and symmetric C-C stretching modes allows the quantitative characterization of the number and length of alkyl chains (i.e., two structural characteristics), upon which the pour point and viscosity of the hydrocarbons depend, and to distinguish these compounds from both each other and linear alkanes. We demonstrated that the ratio of the contents of CH and CH groups in these hydrocarbons can be determined by using the intensities of the bands in the spectra, related to the asymmetric stretching vibrations of these groups. The density functional theory (DFT) calculations were applied to reveal the relations between the wavenumber and bandshape of the symmetric C-C stretching mode and a conformation arrangement of the 1-hexene and 1-octene dimers. We found that the branched double-chain conformation results in the splitting of the C-C mode into two components with the wavenumbers, which can be used as a measure of the length of branches. This conformation is preferable to the extended-chain conformation for hydrogenated 1-hexene and 1-octene dimers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/polym12092153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570275PMC
September 2020

Histological validation of in vivo assessment of cancer tissue inhomogeneity and automated morphological segmentation enabled by Optical Coherence Elastography.

Sci Rep 2020 07 16;10(1):11781. Epub 2020 Jul 16.

Institute of Applied Physics, Russian Academy of Sciences, Ulyanov Street 46, Nizhny Novgorod, 603950, Russia.

We present a non-invasive (albeit contact) method based on Optical Coherence Elastography (OCE) enabling the in vivo segmentation of morphological tissue constituents, in particular, monitoring of morphological alterations during both tumor development and its response to therapies. The method uses compressional OCE to reconstruct tissue stiffness map as the first step. Then the OCE-image is divided into regions, for which the Young's modulus (stiffness) falls in specific ranges corresponding to the morphological constituents to be discriminated. These stiffness ranges (characteristic "stiffness spectra") are initially determined by careful comparison of the "gold-standard" histological data and the OCE-based stiffness map for the corresponding tissue regions. After such pre-calibration, the results of morphological segmentation of OCE-images demonstrate a striking similarity with the histological results in terms of percentage of the segmented zones. To validate the sensitivity of the OCE-method and demonstrate its high correlation with conventional histological segmentation we present results obtained in vivo on a murine model of breast cancer in comparative experimental study of the efficacy of two antitumor chemotherapeutic drugs with different mechanisms of action. The new technique allowed in vivo monitoring and quantitative segmentation of (1) viable, (2) dystrophic, (3) necrotic tumor cells and (4) edema zones very similar to morphological segmentation of histological images. Numerous applications in other experimental/clinical areas requiring rapid, nearly real-time, quantitative assessment of tissue structure can be foreseen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-68631-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366713PMC
July 2020

Indium iodide single crystal: breakthrough material for infrared acousto-optics.

Opt Lett 2020 Jul;45(13):3435-3438

Measurements of the refractive indices and the full set of longitudinal acousto-optical figures of merit in an orthorhombic single-crystal indium iodide (InI) were carried out. The high acousto-optic characteristics ( up to 1100×10) and strong optical anisotropy (=0.47) make it possible to design various types of high-performance acousto-optic devices of the middle and far-infrared spectral range. In combination with a wide transparency range (0.62-51µ), the obtained characteristics make the crystal extremely promising in comparison with most existing analogs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OL.393737DOI Listing
July 2020

A structural-based computational model of tendon-bone insertion tissues.

Math Biosci 2020 09 2;327:108411. Epub 2020 Jul 2.

North Carolina State University, United States of America. Electronic address:

Tendon-to-bone insertion provides a gradual transition from soft tendon to hard bone tissue, functioning to alleviate stress concentrations at the junction of these tissues. Such macroscopic mechanical properties are achieved due to the internal structure in which collagen fibers and mineralization levels are key ingredients. We develop a structural-based model of tendon-to-bone insertion incorporating such details as fiber preferred orientation, fiber directional dispersion, mineralization level, and their inhomogeneous spatial distribution. A python script is developed to alter the tapered tendon-bone transition zone and to provide spatial grading of material properties, which may be rather complex as experiments suggest. A simple linear interpolation between tendon and bone material properties is first used to describe the graded property within the insertion region. Stress distributions are obtained and compared for spatially graded and various piece-wise materials properties. It is observed that spatial grading results in more smooth stress distributions and significantly reduces maximum stresses. The geometry of the tissue model is optimized by minimizing the peak stress to mimic in-vivo tissue remodeling. The in-silico elastic models constructed in this work are verified and modified by comparing to our in-situ biaxial mechanical testing results, thereby serving as translational tools for accurately predicting the material behavior of the tendon-to-bone insertions. This model will be useful for understanding how tendon-to-bone insertion develops during tissue remodeling, as well as for developing orthopedic implants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mbs.2020.108411DOI Listing
September 2020

Frontiers in urethra regeneration: current state and future perspective.

Biomed Mater 2020 Jun 5. Epub 2020 Jun 5.

Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, UNITED STATES.

Despite the positive achievements attained, the treatment of male urethral strictures and hypospadiases still remains a challenge, particularly, in cases of severe urethral defects. Complication rate and need for additional interventions in such cases are the highest. Also, shortage of autologous tissue for graft harvesting and significant morbidity on the place of harvesting present a problem and often lead to staged treatment. Tissue engineering provides a promising alternative to the current sources of grafts for urethroplasty. Since the first experiments in urethral substitution with tissue engineered grafts, this topic in regenerative medicine has grown remarkably, as many different types of tissue engineered grafts and approaches in graft design have been suggested and tested in vivo. However, there have been only several clinical trials of tissue engineered grafts in urethral substitution with hardly more than hundred patients overall. This indicates that the topic is still in its inception, and the searching for the best graft design is continuing. The current review focuses on the state of art in urethral regeneration with tissue engineering technology. It gives comprehensive overview of components of the tissue engineered graft and overview of steps in the graft development. Different cell sources, types of scaffolds, assembling approaches, options for vascularization enhancement and preclinical models are considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1748-605X/ab99d2DOI Listing
June 2020

A complex morphofunctional approach for zinc toxicity evaluation in rats.

Heliyon 2020 Apr 21;6(4):e03768. Epub 2020 Apr 21.

I.M. Sechenov First Moscow State Medical University (Sechenov University), Russian Federation.

Anthropogenic activity causes the introduction of zinc compounds into the biological cycle in mining and processing sites and its accumulation in organs and tissues, causing systemic toxicity. A cumulative effect of zinc is predominantly neurotoxic and it also affects the respiratory, cardiovascular and digestive systems. This study evaluates the effects of single-dose intragastric administration of 100 mg/kg zinc succinate on the structure and function of organs and tissues in male Wistar rats 1 month after treatment. The presented morphofunctional approach for the toxicity evaluation included the study of behavioral responses using the automated Laboras® complex, fluorescent spectral analysis of the NADH and FAD activity and histological evaluation of animal organs and tissues. The results of the behavioral activity assessment showed a significant decrease in animals' motor activity, whereas the fluorescence spectra analysis demonstrated a decrease in coenzyme NADH without the reduction of FAD levels. We detected toxic and dystrophic changes in the cerebral cortex, heart, lungs and liver tissues. Our original multiparametric approach enables a comprehensive assessment of the long-term toxic effects of the metal salts such as zinc succinate, especially in the cerebral cortex at the doses much lower than the acute LD reported for the common zinc salts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2020.e03768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177034PMC
April 2020

assessment of functional and morphological alterations in tumors under treatment using OCT-angiography combined with OCT-elastography.

Biomed Opt Express 2020 Mar 13;11(3):1365-1382. Epub 2020 Feb 13.

Institute of Applied Physics RAS, Nizhny Novgorod, Russia.

Emerging methods of anti-tumor therapies require new approaches to tumor response evaluation, especially enabling label-free diagnostics and utilization. Here, to assess the tumor early reaction and predict its long-term response, for the first time we apply in combination the recently developed OCT extensions - optical coherence angiography (OCA) and compressional optical coherence elastography (OCE), thus enabling complementary functional/microstructural tumor characterization. We study two vascular-targeted therapies of different types, (1) anti-angiogenic chemotherapy (ChT) and (2) photodynamic therapy (PDT), aimed to indirectly kill tumor cells through blood supply injury. Despite different mechanisms of anti-angiogenic action for ChT and PDT, in both cases OCA demonstrated high sensitivity to blood perfusion cessation. The new method of OCE-based morphological segmentation revealed very similar histological structure alterations. The OCE results showed high correlation with conventional histology in evaluating percentages of necrotic and viable tumor zones. Such possibilities make OCE an attractive tool enabling previously inaccessible monitoring of individual tumor response to therapies without taking multiple biopsies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/BOE.386419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075625PMC
March 2020

Cross-Polarization Optical Coherence Tomography for Brain Tumor Imaging.

Front Oncol 2019 2;9:201. Epub 2019 Apr 2.

Laboratory of Optical Coherence Tomography, Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, Nizhny Novgorod, Russia.

This paper considers valuable visual assessment criteria for distinguishing between tumorous and non-tumorous tissues, intraoperatively, using cross-polarization OCT (CP OCT)-OCT with a functional extension, that enables detection of the polarization properties of the tissues in addition to their conventional light scattering. The study was performed on 176 human specimens obtained from 30 glioma patients. To measure the degree to which the typical parameters of CP OCT images can be matched to the actual histology, 100 images of tumors and white matter were selected for visual analysis to be undertaken by three "single-blinded" investigators. An evaluation of the inter-rater reliability between the investigators was performed. Application of the identified visual CP OCT criteria for intraoperative use was performed during brain tumor resection in 17 patients. The CP OCT image parameters that can typically be used for visual assessment were separated: (1) signal intensity; (2) homogeneity of intensity; (3) attenuation rate; (4) uniformity of attenuation. The degree of match between the CP OCT images and the histology of the specimens was significant for the parameters "signal intensity" in both polarizations, and "homogeneity of intensity" as well as the "uniformity of attenuation" in co-polarization. A test based on the identified criteria showed a diagnostic accuracy of 87-88%. Intraoperative CP OCT images of white matter and tumors have similar signals to ones, whereas the cortex is characterized by indicative vertical striations arising from the "shadows" of the blood vessels; these are not seen in images or in the case of tumor invasion. Visual assessment of CP OCT images enables tumorous and non-tumorous tissues to be distinguished. The most powerful aspect of CP OCT images that can be used as a criterion for differentiation between tumorous tissue and white matter is the signal intensity. In distinguishing white matter from tumors the diagnostic accuracy using the identified visual CP OCT criteria was 87-88%. As the CP OCT data is easily associated with intraoperative neurophysiological and neuronavigation findings this can provide valuable complementary information for the neurosurgeon tumor resection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.00201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455095PMC
April 2019

Quantitative nontumorous and tumorous human brain tissue assessment using microstructural co- and cross-polarized optical coherence tomography.

Sci Rep 2019 02 14;9(1):2024. Epub 2019 Feb 14.

Privolzhsky Research Medical University, 603950 Minin and Pozharsky Sq., 10/1, Nizhny Novgorod, Russia.

Optical coherence tomography (OCT) is a promising method for detecting cancer margins during tumor resection. This study focused on differentiating tumorous from nontumorous tissues in human brain tissues using cross-polarization OCT (CP OCT). The study was performed on fresh ex vivo human brain tissues from 30 patients with high- and low-grade gliomas. Different tissue types that neurosurgeons should clearly distinguish during surgery, such as the cortex, white matter, necrosis and tumorous tissue, were separately analyzed. Based on volumetric CP OCT data, tumorous and normal brain tissue were differentiated using two optical coefficients - attenuation and forward cross-scattering. Compared with white matter, tumorous tissue without necrotic areas had significantly lower optical attenuation and forward cross-scattering values. The presence of particular morphological patterns, such as necrosis and injured myelinated fibers, can lead to dramatic changes in coefficient values and create some difficulties in differentiating between tissues. Color-coded CP OCT maps based on optical coefficients provided a visual assessment of the tissue. This study demonstrated the high translational potential of CP OCT in differentiating tumorous tissue from white matter. The clinical use of CP OCT during surgery in patients with gliomas could increase the extent of tumor resection and improve overall and progression-free survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-38493-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375924PMC
February 2019

Strain state dependent anisotropic viscoelasticity of tendon-to-bone insertion.

Math Biosci 2019 02 8;308:1-7. Epub 2018 Dec 8.

Mechanical and Aerospace Engineering Department, North Carolina State University, R3158 Engineering Building 3, Campus Box 7910, 911 Oval Drive, Raleigh, NC 27695, United States. Electronic address:

Tendon-to-bone insertion tissues may be considered as functionally-graded connective tissues, providing a gradual transition from soft tendon to hard bone tissue, and functioning to alleviate stress concentrations at the junction of these tissues. The tendon-to-bone insertion tissues demonstrate pronounced viscoelastic behavior, like many other biological tissues, and are designed by the nature to alleviate stress at physiological load rates and strains states. In this paper we present experimental data showing that under biaxial tension tendon-to-bone insertion demonstrates rate-dependent behavior and that stress-strain curves for the in-plane components of stress and strain become less steep when strain rate is increased, contrary to a typical viscoelastic behavior, where the opposite trend is observed. Such behavior may indicate the existence of a protective viscoelastic mechanism reducing stress and strain during a sudden increase in mechanical loading, known to exist in some biological tissues. The main purpose of the paper is to show that such viscoelastic stress reduction indeed possible and is thermodynamically consistent. We, therefore, propose an anisotropic viscoelasticity model for finite strain. We identify the range of parameters for this model which yield negative viscoelastic contribution into in-plane stress under biaxial state of strain and simultaneously satisfy requirements of thermodynamics. We also find optimal parameters maximizing the observed protective viscoelastic effect for this particular state of strain. This model will be useful for testing and describing viscoelastic materials and for developing interfaces for dissimilar materials, considering rate effect and multiaxial loadings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mbs.2018.12.007DOI Listing
February 2019

Response to: The GPRC5A frameshift variant c.183del is not associated with increased breast cancer risk in BRCA1 mutation carriers.

Int J Cancer 2019 04 6;144(7):1758-1760. Epub 2019 Jan 6.

Department of Tumor Growth Biology, N.N. Petrov Institute of Oncology, Saint Petersburg, Russia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.32013DOI Listing
April 2019

Quantitative assessment of radiation-induced changes of bladder and rectum collagen structure using optical methods.

J Biomed Opt 2018 08;23(9):1-8

Nizhny Novgorod State Medical Academy (NNSMA), Department of Oncology, Radiation Therapy, Radiation, Russia.

The objective of the study is the quantitative analysis of the dose-time dependences of changes occurring in collagen of bladder and rectum after gamma-irradiation using optical methods [nonlinear microscopy in a second harmonic generation (SHG) detection regime and cross-polarization optical coherence tomography (CP OCT)]. For quantitative assessment of the collagen structure, regions of interest on the SHG-images of two-dimensional (2-D) distribution of SHG signal intensity of collagen were chosen in the submucosa. The mean SHG signal intensity and its standard deviation were calculated by ImageJ 1.39p (NIH). For quantitative analysis of CP OCT data, an integral depolarization factor (IDF) was calculated. Quantitative calculation of the SHG signal intensity and the IDF can provide additional information about the processes of the collagen radiation-induced degradation and subsequent remodeling. High positive correlation between the mean SHG signal intensity and the mean IDF of bladder and rectum demonstrates that CP OCT can be used as an "optical biopsy" in the grading of collagen radiation damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1117/1.JBO.23.9.091417DOI Listing
August 2018

Primary hyperparathyroidism in young patients in Russia: high frequency of hyperparathyroidism-jaw tumor syndrome.

Endocr Connect 2017 Nov 4;6(8):557-565. Epub 2017 Sep 4.

Department and Laboratory of Inherited Endocrine DisordersEndocrinology Research Center, Moscow, Russian Federation.

Background: Primary hyperparathyroidism (PHPT) is a relatively rare disorder among children, adolescents and young adults. Its development at an early age is suspicious for hereditary causes, though the need for routine genetic testing remains controversial.

Objective: To identify and describe hereditary forms of PHPT in patients with manifestation of the disease under 40 years of age.

Design: We enrolled 65 patients with PHPT diagnosed before 40 years of age. Ten of them had mutation, and PHPT in them was the first manifestation of multiple endocrine neoplasia type 1 syndrome.

Methods: The other fifty-five patients underwent next-generation sequencing (NGS) of a custom-designed panel of genes, associated with PHPT (, , , , , , , , ). In cases suspicious for gross deletions multiplex ligation-dependent probe amplification was performed.

Results: NGS revealed six pathogenic or likely pathogenic germline sequence variants: four in c.271C>T (p.Arg91*), c.496C>T (p.Gln166*), c.685A>T (p.Arg229*) and c.787C>T (p.Arg263Cys); one in c.3145G>T (p.Glu1049*) and one in c.784-9G>A. In two patients, MLPA confirmed gross deletions. In total, 44 sporadic and 21 hereditary PHPT cases were identified. Parathyroid carcinomas and atypical parathyroid adenomas were present in 8/65 of young patients, in whom mutations were found in 5/8.

Conclusions: Hereditary forms of PHPT can be identified in up to 1/3 of young patients with manifestation of the disease at <40 years of age. Parathyroid carcinomas or atypical parathyroid adenomas in young patients are frequently associated with mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1530/EC-17-0126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633061PMC
November 2017

Pixel classification method in optical coherence tomography for tumor segmentation and its complementary usage with OCT microangiography.

J Biophotonics 2018 04 18;11(4):e201700072. Epub 2017 Dec 18.

Nano-optics and Highly Sensitive Optical Measurement Department, Institute of Applied Physics Russian Academy of Sciences, Nizhny Novgorod, Russia.

A novel machine-learning method to distinguish between tumor and normal tissue in optical coherence tomography (OCT) has been developed. Pre-clinical murine ear model implanted with mouse colon carcinoma CT-26 was used. Structural-image-based feature sets were defined for each pixel and machine learning classifiers were trained using "ground truth" OCT images manually segmented by comparison with histology. The accuracy of the OCT tumor segmentation method was then quantified by comparing with fluorescence imaging of tumors expressing genetically encoded fluorescent protein KillerRed that clearly delineates tumor borders. Because the resultant 3D tumor/normal structural maps are inherently co-registered with OCT derived maps of tissue microvasculature, the latter can be color coded as belonging to either tumor or normal tissue. Applications to radiomics-based multimodal OCT analysis are envisioned.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbio.201700072DOI Listing
April 2018

Seed-effect modeling improves the consistency of genome-wide loss-of-function screens and identifies synthetic lethal vulnerabilities in cancer cells.

Genome Med 2017 06 1;9(1):51. Epub 2017 Jun 1.

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.

Background: Genome-wide loss-of-function profiling is widely used for systematic identification of genetic dependencies in cancer cells; however, the poor reproducibility of RNA interference (RNAi) screens has been a major concern due to frequent off-target effects. Currently, a detailed understanding of the key factors contributing to the sub-optimal consistency is still a lacking, especially on how to improve the reliability of future RNAi screens by controlling for factors that determine their off-target propensity.

Methods: We performed a systematic, quantitative analysis of the consistency between two genome-wide shRNA screens conducted on a compendium of cancer cell lines, and also compared several gene summarization methods for inferring gene essentiality from shRNA level data. We then devised novel concepts of seed essentiality and shRNA family, based on seed region sequences of shRNAs, to study in-depth the contribution of seed-mediated off-target effects to the consistency of the two screens. We further investigated two seed-sequence properties, seed pairing stability, and target abundance in terms of their capability to minimize the off-target effects in post-screening data analysis. Finally, we applied this novel methodology to identify genetic interactions and synthetic lethal partners of cancer drivers, and confirmed differential essentiality phenotypes by detailed CRISPR/Cas9 experiments.

Results: Using the novel concepts of seed essentiality and shRNA family, we demonstrate how genome-wide loss-of-function profiling of a common set of cancer cell lines can be actually made fairly reproducible when considering seed-mediated off-target effects. Importantly, by excluding shRNAs having higher propensity for off-target effects, based on their seed-sequence properties, one can remove noise from the genome-wide shRNA datasets. As a translational application case, we demonstrate enhanced reproducibility of genetic interaction partners of common cancer drivers, as well as identify novel synthetic lethal partners of a major oncogenic driver, PIK3CA, supported by a complementary CRISPR/Cas9 experiment.

Conclusions: We provide practical guidelines for improved design and analysis of genome-wide loss-of-function profiling and demonstrate how this novel strategy can be applied towards improved mapping of genetic dependencies of cancer cells to aid development of targeted anticancer treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13073-017-0440-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452371PMC
June 2017

Rapid selection of BRCA1-proficient tumor cells during neoadjuvant therapy for ovarian cancer in BRCA1 mutation carriers.

Cancer Lett 2017 07 1;397:127-132. Epub 2017 Apr 1.

Department of Tumor Biology, N.N. Petrov Institute of Oncology, St.-Petersburg 197758, Russia; Department of Medical Genetics, St.-Petersburg Pediatric Medical University, St.-Petersburg 194100, Russia; Department of Medical Genetics, I.I. Mechnikov North-Western Medical University, St.-Petersburg 191015, Russia; Department of Oncology, St.-Petersburg State University, St.-Petersburg 199034, Russia. Electronic address:

Ovarian carcinomas (OC) often demonstrate rapid tumor shrinkage upon neoadjuvant chemotherapy (NACT). However, complete pathologic responses are very rare and the mechanisms underlying the emergence of residual tumor disease remain elusive. We hypothesized that the change of somatic BRCA1 status may contribute to this process. The loss-of-heterozygosity (LOH) at the BRCA1 locus was determined for 23 paired tumor samples obtained from BRCA1 germ-line mutation carriers before and after NACT. We observed a somatic loss of the wild-type BRCA1 allele in 74% (17/23) of OCs before NACT. However, a retention of the wild-type BRCA1 copy resulting in a reversion of LOH status was detected in 65% (11/17) of those patients after NACT. Furthermore, we tested 3 of these reversion samples for LOH at intragenic BRCA1 single nucleotide polymorphisms (SNPs) and confirmed a complete restoration of the SNP heterozygosity in all instances. The neoadjuvant chemotherapy for BRCA1-associated OC is accompanied by a rapid expansion of pre-existing BRCA1-proficient tumor clones suggesting that continuation of the same therapy after NACT and surgery may not be justified even in patients initially experiencing a rapid tumor regression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2017.03.036DOI Listing
July 2017

Linear parabolic single-crystal diamond refractive lenses for synchrotron X-ray sources.

J Synchrotron Radiat 2017 01 1;24(Pt 1):103-109. Epub 2017 Jan 1.

Immanuel Kant Baltic Federal University, 14 Nevskogo, Kaliningrad 236041, Russian Federation.

Linear parabolic diamond refractive lenses are presented, designed to withstand high thermal and radiation loads coming from upgraded accelerator X-ray sources. Lenses were manufactured by picosecond laser treatment of a high-quality single-crystal synthetic diamond. Twelve lenses with radius of curvature at parabola apex R = 200 µm, geometrical aperture A = 900 µm and length L = 1.5 mm were stacked as a compound refractive lens and tested at the ESRF ID06 beamline. A focal spot of size 2.2 µm and a gain of 20 were measured at 8 keV. The lens profile and surface quality were estimated by grating interferometry and X-ray radiography. In addition, the influence of X-ray glitches on the focusing properties of the compound refractive lens were studied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S1600577516017331DOI Listing
January 2017

Orphan G protein-coupled receptor GPRC5A modulates integrin β1-mediated epithelial cell adhesion.

Cell Adh Migr 2017 Sep 6;11(5-6):434-446. Epub 2017 Feb 6.

a Institute for Molecular Medicine Finland (FIMM), University of Helsinki , Helsinki , Finland.

G-Protein Coupled Receptor (GPCR), Class C, Group 5, Member A (GPRC5A) has been implicated in several malignancies. The underlying mechanisms, however, remain poorly understood. Using a panel of human cell lines, we demonstrate that CRISPR/Cas9-mediated knockout and RNAi-mediated depletion of GPRC5A impairs cell adhesion to integrin substrates: collagens I and IV, fibronectin, as well as to extracellular matrix proteins derived from the Engelbreth-Holm-Swarm (EHS) mouse sarcoma (Matrigel). Consistent with the phenotype, knock-out of GPRC5A correlated with a reduced integrin β1 (ITGB1) protein expression, impaired phosphorylation of the focal adhesion kinase (FAK), and lower activity of small GTPases RhoA and Rac1. Furthermore, we provide the first evidence for a direct interaction between GPRC5A and a receptor tyrosine kinase EphA2, an upstream regulator of FAK, although its contribution to the observed adhesion phenotype is unclear. Our findings reveal an unprecedented role for GPRC5A in regulation of the ITGB1-mediated cell adhesion and it's downstream signaling, thus indicating a potential novel role for GPRC5A in human epithelial cancers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/19336918.2016.1245264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810789PMC
September 2017

30-Lens interferometer for high-energy X-rays.

J Synchrotron Radiat 2016 09 9;23(Pt 5):1104-9. Epub 2016 Aug 9.

Baltic Federal University, Kaliningrad 236041, Russian Federation.

A novel high-energy multi-lens interferometer consisting of 30 arrays of planar compound refractive lenses is reported. Under coherent illumination each lens array creates a diffraction-limited secondary source. Overlapping such coherent beams produces an interference pattern demonstrating strong longitudinal functional dependence. The proposed multi-lens interferometer was tested experimentally at the 100 m-long ID11 ESRF beamline in the X-ray energy range from 30 to 65 keV. The interference pattern generated by the interferometer was recorded at fundamental and fractional Talbot distances. An effective source size (FWHM) of the order of 15 µm was determined from the first Talbot image, proving the concept that the multi-lens interferometer can be used as a high-resolution tool for beam diagnostics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1107/S160057751601153XDOI Listing
September 2016

Numerical test for hyperbolicity of chaotic dynamics in time-delay systems.

Phys Rev E 2016 Jul 1;94(1-1):010201. Epub 2016 Jul 1.

Institute of Mathematics, Information Technologies and Physics, Udmurt State University, Universitetskaya 1, Izhevsk, 426034, Russia.

We develop a numerical test of hyperbolicity of chaotic dynamics in time-delay systems. The test is based on the angle criterion and includes computation of angle distributions between expanding, contracting, and neutral manifolds of trajectories on the attractor. Three examples are tested. For two of them, previously predicted hyperbolicity is confirmed. The third one provides an example of a time-delay system with nonhyperbolic chaos.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1103/PhysRevE.94.010201DOI Listing
July 2016

BRCA1-deficient breast cancer cell lines are resistant to MEK inhibitors and show distinct sensitivities to 6-thioguanine.

Sci Rep 2016 06 17;6:28217. Epub 2016 Jun 17.

Institute for Molecular Medicine Finland (FIMM), University of Helsinki, PO Box 20, FIN-00014, Helsinki, Finland.

Germ-line or somatic inactivation of BRCA1 is a defining feature for a portion of human breast cancers. Here we evaluated the anti-proliferative activity of 198 FDA-approved and experimental drugs against four BRCA1-mutant (HCC1937, MDA-MB-436, SUM1315MO2, and SUM149PT) and four BRCA1-wild-type (MDA-MB-231, SUM229PE, MCF10A, and MCF7) breast cancer cell lines. We found that all BRCA1-mutant cell lines were insensitive to inhibitors of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) Selumetinib and Pimasertib in contrast to BRCA1-wildtype control cell lines. However, unexpectedly, only two BRCA1-mutant cell lines, HCC1937 and MDA-MB-436, were hypersensitive to a nucleotide analogue 6-thioguanine (6-TG). SUM149PT cells readily formed radiation-induced RAD51-positive nuclear foci indicating a functional homologous recombination, which may explain their resistance to 6-TG. However, the reason underlying 6-TG resistance of SUM1315MO2 cells remains unclear. Our data reveal a remarkable heterogeneity among BRCA1-mutant cell lines and provide a reference for future studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep28217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911578PMC
June 2016

Prolonged dry apnoea: effects on brain activity and physiological functions in breath-hold divers and non-divers.

Eur J Appl Physiol 2016 Jul 17;116(7):1367-77. Epub 2016 May 17.

Institute of Biomedical Problems of the Russian Academy of Sciences, 123007, Khoroshevskoye Sh., 76A, Moscow, Russia.

Purpose: The aim of the study was to investigate the effects of voluntary breath-holding on brain activity and physiological functions. We hypothesised that prolonged apnoea would trigger cerebral hypoxia, resulting in a decrease of brain performance; and the apnoea's effects would be more pronounced in breath-hold divers.

Methods: Trained breath-hold divers and non-divers performed maximal dry breath-holdings. Lung volume, alveolar partial pressures of O2 and CO2, attention and anxiety levels were estimated. Heart rate, blood pressure, arterial blood oxygenation, brain tissue oxygenation, EEG, and DC potential were monitored continuously during breath-holding.

Results: There were a few significant changes in electrical brain activity caused by prolonged apnoea. Brain tissue oxygenation index and DC potential were relatively stable up to the end of the apnoea in breath-hold divers and non-divers. We also did not observe any decrease of attention level or speed of processing immediately after breath-holding. Interestingly, trained breath-hold divers had some peculiarities in EEG activity at resting state (before any breath-holding): non-spindled, sharpened alpha rhythm; slowed-down alpha with the frequency nearer to the theta band; and untypical spatial pattern of alpha activity.

Conclusion: Our findings contradicted the primary hypothesis. Apnoea up to 5 min does not lead to notable cerebral hypoxia or a decrease of brain performance in either breath-hold divers or non-divers. It seems to be the result of the compensatory mechanisms similar to the diving response aimed at centralising blood circulation and reducing peripheral O2 uptake. Adaptive changes during apnoea are much more prominent in trained breath-hold divers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00421-016-3390-2DOI Listing
July 2016