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Introduction. The formation of circulating autoantibodies capable of inhibiting factors of the blood coagulation system is accompanied by the occurrence of spontaneous and/or post-traumatic bleeding in patients without a history of previous disorders of the hemostasis system. One of the reasons for the development of such conditions is acquired hemophilia.Aim – to present algorithms for laboratory diagnosis of acquired hemophilia.Main findings. Primary diagnosis and control of therapy of the disease are carried out based on the results of coagulation studies, the decoding and interpretation of which often causes difficulties due to the low awareness of doctors about the algorithms for laboratory diagnosis and tactics for managing patients. In acquired hemophilia there is no direct relationship between the results of laboratory tests and the clinical manifestations of the disease, which is determined by the kinetics of the interaction of autoantibodies with blood coagulation factor (F) VIII. There is a «false» in vitro decrease in the activity of factors of the internal pathway (FIX, FXI and FXII), associated with the effect of a rapid inhibitor in high titers. An important laboratory task is the determination of lupus anticoagulant, which makes it difficult to timely diagnose and verify the diagnosis.

Inductive hyperthermia treatment plans were built using Comsol Multiphysics software for patients with breast cancer metastasis to lymph nodes. To assess the influence of electromagnetic irradiation on temperature increase in metastatic lymph nodes, treatment plans were based on moderate hyperthermia parameters (< 42 °C). The proposed technology can be used to provide a more personalized approach to treatment planning for patients with locally advanced breast cancer receiving combination therapy which involves neoadjuvant chemotherapy and expand eligibility for organ-preserving surgery.

OBJECTIVE This study aimed to determine whether texture parameters could be used in differentiation between the tumor and the peritumoral tissues based on hybrid 18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging for patients with rectal cancer. METHODS Seven parameters, including heterogeneity, entropy, energy, skewness, kurtosis, standard deviation, and average brightness, were extracted from positron emission tomography/computed tomography scans of 22 patients (12 male and 10 female; mean age, 61 ± 2 years). RESULTS The peritumoral tissue had a significantly lower value of the heterogeneity parameter (23%) than the tumor. Tumor size (r = -0.48, P < 0.05) and extramural venous invasion scores (r = 0.64, P < 0.05) correlated with heterogeneity in the peritumoral tissue. There were significant differences (P < 0.05) in the correlation coefficients between men and women. CONCLUSIONS Therefore, we provided additional quantitative information to differentiate the tumor from the peritumoral tissue and indicated possible application for extramural venous invasion evaluation in rectal cancer.

Magnetic nanoparticles (MNs) are typically used as contrast agents for magnetic resonance imaging or as drug carriers with a remotely controlled delivery to the tumor. However, they can also potentiate the action of anticancer drugs under the influence of applied constant magnetic (CMFs) and electromagnetic fields (EMFs). This review demonstrates the role of magneto-mechanochemical effects produced by MNs alone and loaded with anticancer agents (MNCs) in response to CMFs and EMFs for modulation of tumor redox state. The combined treatment is suggested to act by two mechanisms: spin-dependent electron transport propagates free radical chain reactions, while magnetomechanical interactions cause conformational changes in drug molecules loaded onto MNs and generate reactive oxygen species (ROS). By adjusting the parameters of CMFs and EMFs during the magneto-mechanochemical synthesis and subsequent treatment, it is possible to modulate ROS production and switch redox signaling involved in ERK1/2 and NF-κB pathways from initiation of tumor growth to inhibition. Observations of tumor volume in different animal models and treatment combinations reported a 6%-70% reduction as compared with conventional drugs. Despite these results, there is a general lack of research in magnetic nanotheranostics that link redox changes across multiple levels of organization in the tumor-bearing host. Further multidisciplinary studies with more focus on the relationship between the electron transport processes in biomolecules and their effects on the tumor-host interaction should accelerate the clinical translation of magnetic nanotheranostics. This article is categorized under: Therapeutic Approaches and Drug DiscoveryNanomedicine for Oncologic Disease Therapeutic Approaches and Drug DiscoveryEmerging Technologies Nanotechnology Approaches to BiologyNanoscale Systems in Biology.

The mechanism of aldol condensation of ketones in KOH/DMSO superbasic media has been investigated using the B2PLYP(D2)/6-311+G**//B3LYP/6-31+G* quantum-chemical approach. It is found that the interaction of three ketone molecules resulting in the formation of the cyclohex-2-enone structure [isophorone or 3,5-dicyclohexyl-5-methylspiro(5.5)undec-2-en-1-one] is thermodynamically more favorable than the interaction of two, three, or four molecules of ketone, resulting in the formation of linear products of the condensation. The formation of the condensation products with the isophorone skeleton can significantly hinder the cascade reactions of ketones with acetylenes [to afford 6,8-dioxabicyclo(3.2.1)octanes or acylcyclopentenols] promoted by superbases. In particular, the kinetically more preferable reactions of autovinylation of 2-methyl-3-butyn-2-ol and autocondensation of acetone are the reasons why interaction of acetone with acetylene does not lead to the products of the cascade assemblies. The predominant formation of the products of these side reactions is confirmed experimentally.

Introduction. Among the most common congenital coagulopathies are haemophilia and Von Willebrand disease. These illnesses are often mimicked by orphan hereditary coagulopathies, including combined coagulation factor V and VIII deficiency.Aim — description of a clinical presentation, hampered diagnosis and choice of haemostatic therapy in a surgical patient with combined blood coagulation factor V and VIII deficiency.Main findings. We describe a clinical case of congenital combined factor V and VIII deficiency and detail the aetiology, frequency, localisation and intensity of haemorrhages. Comorbidity and surgical indications are demonstrated to require an inter-specialty medical involvement.

By employing the contemporary B2PLYP(D3)/6-311+G**//B3LYP/6-31+G* method of quantum chemistry, we unraveled the mechanism of a recently discovered cascade assembly of N-phenyl-2,5-dimethylpyrrole from one molecule of aniline and three molecules of acetylene activated by KOH/DMSO and KOBut/DMSO superbase systems. For the established mechanism, we compare and analyze the activity of these two superbases. The reaction is found to be activated by the interaction of aniline with acetylene, and the barrier associated with this interaction turns out to be the limiting one. Another barrier close in value to the limiting one is found along the cascade assembly pathway and relates to ethynylation of N-but-3-yn-2-yl-aniline by the ethynide ion. The cascade reaction turns out to be selective with respect to propyne-allene rearrangements. The alternative mechanism of N-phenyl-2,5-dimethylpyrrole self-assembly, which involves a preliminary stage of acetylene oligomerization, is shown to be kinetically less favorable.

The biological and medical aspects of magnetochemical effects in nanotherapy of tumors remain poorly studied. The present paper investigates the influence of nonlinear magnetochemical effects of anisotropic magnetic nanodots on an animal tumor model. The magnetic properties and electron spin resonance spectra of magnetic nanodots and doxorubicin were investigated after mechano-magnetochemical synthesis. The results obtained from the analysis of nonlinear kinetics and survival in Walker-256 carcinosarcoma-bearing animals found a nonlinear dependence between the value of the growth factor, braking ratio, survival rate, tumor redox state, and the treatment by the magnetic nanodot combined with a nonuniform constant magnetic field. To quantify the heterogeneity in microphotographs of Walker-256 carcinosarcoma sections, we applied the entropy parameter. The control (no treatment) group showed the greatest heterogeneity. The lowest value of tumor heterogeneity among animals given treatment was found in groups with the minimum growth factor. Similarly, the lowest entropy value was found in muscle tissue taken from inoculation areas of the tumor. The evidence from this study concluded that inhomogeneous constant magnetic fields with different strength applied to heterogeneous tumor tissues induced different magnetic anisotropy in the magnetic nanodot which had a significant influence on the nonlinear kinetics, redox state, and histological pattern of the tumor.

With the continuous development of drug screening technology, new screening methodologies and technologies are constantly emerging, driving drug screening into rapid, efficient and high-throughput development. Microfluidics is a rising star in the development of innovative approaches in drug discovery. In this article, we summarize the recent years' progress of microfluidic chip technology in drug screening, including the developmental history, structural design, and applications in different aspects of microfluidic chips on drug screening. Herein, the existing microfluidic chip screening platforms are summarized from four aspects: chip structure design, sample injection and drive system, cell culture technology on a chip, and efficient remote detection technology. Furthermore, this review discusses the application and developmental prospects of using microfluidic chips in drug screening, particularly in screening natural product anticancer drugs based on chemical properties, pharmacological effects, and drug cytotoxicity.

This study aimed to determine whether texture parameters could be used in differentiation between the tumor and the peritumoral tissues based on hybrid 18F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging for patients with rectal cancer.Seven parameters, including heterogeneity, entropy, energy, skewness, kurtosis, standard deviation, and average brightness, were extracted from positron emission tomography/computed tomography scans of 22 patients (12 male and 10 female; mean age, 61 ± 2 years).The peritumoral tissue had a significantly lower value of the heterogeneity parameter (23%) than the tumor. Tumor size (r = -0.48, P0.05) and extramural venous invasion scores (r = 0.64, P0.05) correlated with heterogeneity in the peritumoral tissue. There were significant differences (P0.05) in the correlation coefficients between men and women.Therefore, we provided additional quantitative information to differentiate the tumor from the peritumoral tissue and indicated possible application for extramural venous invasion evaluation in rectal cancer.

The mechanism of aldol condensation of ketones in KOH/DMSO superbasic media has been investigated using the B2PLYP(D2)/6-311+G**//B3LYP/6-31+G* quantum-chemical approach. It is found that the interaction of three ketone molecules resulting in the formation of the cyclohex-2-enone structure [isophorone or 3,5-dicyclohexyl-5-methylspiro(5.5)undec-2-en-1-one] is thermodynamically more favorable than the interaction of two, three, or four molecules of ketone, resulting in the formation of linear products of the condensation. The formation of the condensation products with the isophorone skeleton can significantly hinder the cascade reactions of ketones with acetylenes [to afford 6,8-dioxabicyclo(3.2.1)octanes or acylcyclopentenols] promoted by superbases. In particular, the kinetically more preferable reactions of autovinylation of 2-methyl-3-butyn-2-ol and autocondensation of acetone are the reasons why interaction of acetone with acetylene does not lead to the products of the cascade assemblies. The predominant formation of the products of these side reactions is confirmed experimentally.

Although nanotechnology advances have been exploited for a myriad of purposes, including cancer diagnostics and treatment, still there is little discussion about the mechanisms of remote control. Our main aim here is to explain the possibility of a magnetic field control over magnetic nanocomplexes to improve their delivery, controlled release and antitumor activity. In doing so we considered the nonlinear dynamics of magnetomechanical and magnetochemical effects based on free radical mechanisms in cancer development for future pre-clinical studies.

Purpose:To evaluate the efficacy of neoadjuvant chemotherapy in combination with regional inductive moderate hyperthermia for patients with locally advanced breast cancer.Patients and Methods:200 patients with stage IIB-IIIA breast cancer received neoadjuvant chemotherapy (control group, n = 97) or chemotherapy combined with hyperthermia (experimental group, n = 103). Inductive hyperthermia was set at 27.12 ± 0.16 MHz and the 50 W output power.Results:Thermal and color Doppler ultrasound imaging demonstrated that hyperthermia increased the surface temperature on the breasts to < 4°С while the mean values for systolic blood flow were 3.5 times as high as those prior to treatment. Assessment of tumor size and response found a (31.24 ± 3.85)% reduction in the size of the primary tumor in patients receiving chemotherapy + hyperthermia, while chemotherapy alone showed a (22.95 ± 3.61)% decrease on average (p = 0.034). The rate of objective response increased by 15.9% in the experimental group (р = 0.034) compared with the control group. The patients in the experimental group also had axillary lymph node regression of 14.17% greater than in the control group (p = 0.011). Moreover, the combination treatment allowed to increase the proportion of women eligible for breast-conserving and reconstructive surgery by 13.63% in the experimental group. The viable tumor volume was lower in patients receiving neoadjuvant chemotherapy + hyperthermia (24.4 ± 0.2)% compared with those given chemotherapy alone (30.4 ± 0.25)%. The 10-year overall survival rates were higher (log-rank: p = 0.009) in breast cancer patients who underwent chemotherapy combined with hyperthermia than in patients receiving chemotherapy only.Conclusion:The combination neoadjuvant chemotherapy and the technology of regional inductive moderate hyperthermia improved the efficacy of treatment for patients with locally advanced breast cancer staged IIB-IIIA.

By employing the contemporary B2PLYP(D3)/6-311+G**//B3LYP/6-31+G* method of quantum chemistry, we unraveled the mechanism of a recently discovered cascade assembly of

Modulation of reactive oxygen and nitrogen species in a tumor could be exploited for nanotherapeutic benefits. We investigate the antitumor effect in Walker-256 carcinosarcoma of magnetic nanodots composed of doxorubicin-loaded Fe3O4 nanoparticles combined with electromagnetic fields. Treatment using the magnetic nanodot with the largest hysteresis loop area (3402 erg/g) had the greatest antitumor effect with the minimum growth factor 0.49 ± 0.02 day–1 (compared to 0.58 ± 0.02 day–1 for conventional doxorubicin). Electron spin resonance spectra of Walker-256 carcinosarcoma treated with the nanodots, indicate an increase of 2.7 times of free iron (that promotes the formation of highly reactive oxygen species), using the nanodot with the largest hysteresis loop area, compared to conventional doxorubicin treatment as well as increases in ubisemiquinone, lactoferrin, NO-FeS-proteins. Hence, we provide evidence that the designed magnetic nanodots can modulate the tumor redox state. We discuss the implications of these results for cancer nanotherapy.

Transition-metal-free C-vinylation of acetone with phenylacetylene catalyzed by superbases MOH/DMSO and tBuOM/DMSO (M = Na, K) has been theoretically evaluated in the B3LYP/6-311++G**//B3LYP/6-31+G* approach to rationalize similarities and differences in activity of the above catalytic systems. The close solvate surroundings of sodium and potassium tert-butoxides have been studied. Formation of tBuOM· nDMSO complexes and their structure and thermodynamic stability are discussed in comparison with similar complexes of alkali-metal hydroxides MOH· nDMSO. Activation barriers of the title reaction in the presence of tBuOM· nDMSO complexes are found to be less than those with MOH· nDMSO complexes participating.

The kinetic (free activation energies) and thermodynamic factors, which ensure mild conditions for the ethynylation of imines with acetylenes, have been established by quantum chemical calculations using B2PLYP/6-311 + G**//B3LYP/6-31 + G*. According to the calculations, the alternative route of superbase catalyzed C-vinylation requires harsher reaction conditions as compared to the ethynylation one.

Iron oxide (Fe3O4) magnetic nanoparticles (MNs) delivered to the tumor under the influence of magnetic fields can generate reactive oxygen species (ROS) that affect the activity of mitochondrial enzymes, DNA damage and abnormal cell growth. Previous investigations used rotating magnetic fields to inhibit tumor growth. Herein, we question whether the magneto-mechanical effects of MNs under an inhomogeneous stationary magnetic field (ISMF) can modulate tumor heterogeneity, ROS and growth. Animals with Walker-256 carcinosarcoma in group 1 underwent no treatment (control), group 2 received MNs, while group 3 was treated with MNs + ISMF. MNs were injected with tumor cells. ISMF treatment was given every other day starting 2 days after implantation. MNs + ISMF showed a 51% increase in the tumor growth factor compared with MNs alone. Elevated levels of free iron and superoxide radical as well as decreased lactoferrin and NO-FeS-proteins were measured after MNs + ISMF treatment. The present study provides experimental evidence that the magnetic force exerted by ISMF upon MNs initiates morphological heterogeneity, modulates ROS generation and promotes tumor growth. Therefore, these findings propose to circumvent the negative effects of MNs by a shortened duration of targeted delivery, application of slowly changing ISMFs, and combination of ISMFs with alternating magnetic fields to modulate iron-dependent redox reactions.

The mechanisms of furan formation and the competitive reaction of 1,5-diketone formation from 1-mesitylbut-2-en-1-one (1a) and 1-phenylbut-2-en-1-one (1b) were studied using the B3LYP/6-311++G**//B3LYP/6-31+G* quantum chemical approach taking into account solvation effects in terms of the IEFPCM model. The addition to 1a of the ethynide ion to form β-acetylene enolate ion (2a) occurs with the activation energy ΔG≠ = 13.3 kcal mol–1, while the further intramolecular O-vinylation with the closure of 2a to the dihydrofuran cycle of the dihydrofuran carbanion is the rate-determining step in the reaction pathway of substituted furan formation needing the activation energy G≠ = 19.5 kcal mol–1. The alternative addition of the mesitylethenolate ion to 1a to form the 1,5-diketone carbanion is associated with a higher (by 3.4 kcal mol–1) free activation energy than that of ethynide ion addition. In contrast, in the case of 1b, the addition at the C=C bond of the phenylethenolate ion rather than of the ethynide ion to form the 1,5-diketone carbanion is more preferable, since its activation free energy is 1.5 kcal mol–1 lower. The quantum chemical calculation results are consistent with the experimental data.

A CBS-Q//B3 based study has been carried out to elucidate the mechanism of the KOH/DMSO superbase catalyzed ketones nucleophilic addition to alkyl propargyl and alkyl allenyl ethers yielding, along with (Z)-monoadducts, up to 26% of unexpected (E)-diadducts. The impact of different substrates (alkynes versus allenes) on the reaction mechanism has been discussed in detail. Along with the model reaction of acetone addition to propyne and allene, the addition of acetone and acetophenone to methyl propargyl and methyl allenyl ethers is considered. The limiting reaction stage of the starting ketone carbanion addition to propargyl and allenyl systems occurs with activation energies typical for vinylation of ketones. In contrast, the addition of intermediate α-carbanions to the terminal position of methyl allenyl ether is associated with unusually low activation barriers. The results obtained explain the composition of the reaction products and indicate the participation of mainly the allene form in the reaction.

We measured specific volume and hematocrit of blood clots prepared from the whole blood of patients with hemophilia A and healthy male volunteers. It was shown that in the hematocrit range of 43.5-52.5%, specific volume of the blood clot in hemophilia patients with low level of factor VIII (1-4%) was higher than in volunteers. After injection of factor VIII, specific volume of blood clots in hemophilia patients decreased. Hematocrit of the blood clots derived from the whole blood linearly depended on the mean erythrocyte density in both volunteers (r=-0.74, p=0.01) and patients with factor VIII level of 1-4% (r=-0.95, p

Chaos theory (nonlinear dynamics) defines cancer as a complex adaptive system in which each cyclic point corresponds to the bifurcation at which changes in signaling pathways emerge. Quantitative assessment of chaos in digital medical images such as electron microscopy, histology and cytology sections collected from patients with malignant cutaneous melanoma employed the following calculation parameters: the irregularity of external contours, internal heterogeneity based on brightness distribution of macromo-lecules, chromosomes, organelles, inclusion bodies, cells and tissues, kurtosis, entropy and the asymmetry coefficient. The present study undertook a nonlinear analysis of the chaotic hierarchy of malignant melanoma. However, considerably more studies will need to be carried out to determine the exact interrelationship between different levels of the hierarchy in the biological system. Multidisciplinary collaborations are therefore essential to find evidence to answer questions that remain open to researchers and oncologists.

This paper demonstrates the basic principles and data obtained from experimental studies on the influence of a magnetic nanocomplex (MNC) comprising the antitumor drug doxorubicin and magnetic nanoparticles (NP) combined with simultaneous electromagnetic irradiation (EI) on cancer cell viability based on the magnetic memory effect. The key features of magneto-mechano-chemical synthesis were analyzed. The current investigation was inspired by a series of well-known studies on the role of free radical processes in tumor cell necrosis and apoptosis. The experiments carried out on A-549 human lung cancer cells have shown that nanocomplex (MNC2) with the saturation magnetic moment of 15.8 emu/g initiated a greater antitumor effect than MNC1 with the magnetic moment of 8.4 emu/g on an average of 27%.

The mechanism of one-pot assembly of tetracyclic derivatives of frontalin from cycloaliphatic ketones and acetylene, in superbasic KOH/DMSO medium has been investigated using the quantum-chemical B2PLYP/6-311+G∗∗//B3LYP/6-31+G∗ approach. It is demonstrated that the diastereomeric composition of tetracyclic frontalins is determined at the stage of ethynylation of the intermediate 1,5-diketone, and the violation of the diastereoselectivity of the assembly is associated with comparable activation barriers and rates of ethynylation reaction for different diastereomers. It is shown that the reactions of ethynylation of cyclohexanone and subsequent O-vinylation of propargyl alcohol, which compete with the cascade assembly of tetracyclic frontalins, are thermodynamically and kinetically less favorable.

A quantum-chemical simulation of the mechanism of ethynylation of aldimines with substituted acetylenes was carried out. Kinetic and thermodynamic characteristics of this reaction for various reacting pairs were estimated by the B2PLYPD/6-311+G**//B3LYP/6-31+G * method. It was shown that in the reaction with N-alkylaldimines, the ethynylation barrier was significantly higher than in the reaction with N-arylaldimines. The change in the substituents at acetylene has no effect on the ethynylation barriers.

The reactivity of α,β- and β,γ-unsaturated ketones with respect to the nucleophilic attack by ethylhydrazine in one of the key stages of the formation of 4,5-dihydropyrazole has been studied. It is shown that the addition of the terminal nitrogen atom of ethylhydrazine to the carbonyl group of β,γ- and α,γ-unsaturated ketones with the formation of β,γ- and α,β-unsaturated hydrazones is energetically preferable with the participation of two water molecules. At the same time, the addition of the internal nitrogen of ethylhydrazine to the double C=C bond of the α,β-unsaturated ketone (which is preferable in the presence of one water molecule) to give β-ethylhydrazinyl ketone occurs with a lower activation barrier and is thermodynamically more favorable than the addition to the C=O bond.

The electronic characteristics of substrates (α,β-unsaturated ketones) and reagents (carbanions of ketones and ethynide ions), as well as thermodynamic and kinetic characteristics both their interaction and the formation of final products have been evaluated using the B2PLYP/6-311+G**//B3LYP/6-31+G* and B3LYP/6-311++G**//B3LYP/6-31+G* quantum-chemical approaches. Reactivity indices that adequately describe the electrophilic and nucleophilic properties of the substrates and reagents are proposed. It has been shown that, regardless of the nature of substrates and reagents, the formation of cyclopentenols and furans is thermodynamically favorable, while the presence of bulky substituents leads to an increase in energy during the formation of 6,8-dioxabicyclo[3.2.1]octanes and explains in this case their absence in products. The calculated activation barriers of the competing reactions of the nucleophilic addition of ethynide ions and ketone carbanions to the double C=C bond of α,β-unsaturated ketones are correlated with the observed reaction direction and the proposed reactivity indices.

A mechanism for the synthesis of divinyl sulfide via nucleophilic addition of the hydrogen sulfide anion to acetylene in the MOH (M = Na, K)/DMSO superbasic media has been studied using a quantum chemical approach. A comparative analysis of the consecutive stages of hydrogen sulfide and hydroxide anion addition to acetylene in the same catalytic systems is presented.

Tetracyclic frontalin derivatives are used as precursors of drugs for the therapy and prevention of HIV infections and cancer, as well as antibiotics with a wide spectrum of antibacterial action. A recently proposed method of the preparation of tetracyclic frontalin derivatives from two cycloaliphatic ketone molecules and two acetylene molecules in a superbasic catalytic system KOH/DMSO has opened up an elegant and direct approach to the design of these classes of biologically active compounds. In this work, we carried out a quantum-chemical study of isomerism and thermodynamic stability of intermediates and product of the reaction underlying the aforementioned approach. Particular attention was paid to the issues of diastereomerism and violation of diastereoselectivity of the reaction when replacing alkylaromatic or dialkyl ketones by cycloaliphatic ketones in the reactions with acetylene. Based on the results we propose a possible reason for the experimentally observed formation of a mixture of diastereomers of 14,16-dioxatetracyclohexadecane in the cascade assembly of two cyclohexanone molecules and two acetylene molecules. It is shown that the observed ratio of the 14,16-dioxatetracyclohexadecane diastereomers correlates with the equilibrium ratio of cascade assembly intermediates, the semiketal anion diastereomers.

Purpose: Regional inductive moderate hyperthermia in combination with chemotherapy can improve the therapeutic efficacy in patients with breast cancer with multiple liver metastases. Methods: The study included 103 patients with breast cancer with multiple liver metastases: 53 patients (main group) who received a combined chemotherapy (TC drug combination) and regional inductive moderate hyperthermia treatment and 50 patients (control group) who received chemotherapy (TC drug combination) alone. Regional inductive moderate hyperthermia exploited electromagnetic fields with an operating frequency of 27.17 ± 0.16 MHz and output power of 75 W. Treatment results were assessed by computed tomography and ultrasound imaging. Results: Partial regression was defined as a 30% decrease in the sum of the maximum diameters of investigated tumors. In the current study, partial regression was described in 8 (15.1%) patients assigned to the main group and 2 (4%) patients in the control (P < .05). The process stabilization was reported in 32 (60.4%) patients receiving the combined treatment and 19 (38%) in the control (P < .05). Equally important, tumor progression was observed in 13 (24.5%) patients representing the main group and 29 (58%) in the control. During a 30-minute treatment session, a temperature increase overlaying greater than 90% of the liver projection exposed to electromagnetic irradiation was not exceeding 40°C. Conclusion: The combined regional inductive moderate hyperthermia and chemotherapy treatment increased the overall therapeutic efficacy by 33.9% (χ2 = 12.182; P < .01).

It is well known that the magnetic spin effects during nanotherapy can cause tumor cell apoptosis and necrosis based on redox reactions. The current study was carried out on C57Bl/6 mice with Lewis lung carcinoma. The magnetic nanocomplex administration combined with the impact of magnetic resonance system (1.5 T) showed maximal antitumor and antimetastatic effects. The electron spin resonance spectra have been used as diagnostic markers and recorded a change in the tumor redox state based on chemical species such as NO-FeS-proteins and ubisemiquinone. The technology of magnetic resonance nanotheranostics could potentially allow to improve the antitumor effect of chemotherapeutic agents in disseminated cancer therapy.

The present paper aims to develop an antitumor nanovaccine with magnetosensitive properties. The article describes the ability to manipulate the immune response and improve targeted delivery of the antitumor nanovaccine based on magnetic nanoparticles incapsulated inside dendritic cells under the influence of an external magnetic field. The magnetic field influence upon nanovaccine migration to regional lymph nodes and distribution has been analyzed. The conducted experiments showed up to 14% greater antitumor effect of nanovaccine under magnetic field control compared to the known methods for vaccination.

100°C, 1 h 31+G* approach. Superbasic environment was described in the context of model [3] where the super basic center is represented by the KOH · DMSO (3) complex. The solvent molecule included in the explicit form provides the description of specific solva tion effects, which appear in the formation of K+HO– solvent separated ion pair, the nonspecific effect of the other solvate environment is taken into account in terms of the polarizable continuum model (PCM) [4]. Figure 1 represents the schematic profile of vinylation reactions at the 2 and 6 positions of compound 1. The acidity of aliphatic and alicyclic ketones in dimethyl sulfoxide is rather high (pKa ≈ 23–25 [5]) and the reaction of compound 1 with base 3 leads to formation of weakly bound prereaction complexes 4 and next 2 and 6 methylcyclohexenenolate ions 5a and 5b bound to cationic center

Mechanisms of ethynylation and vinylation of ketones with phenylacetylene in the presence of KOH•5DMSO superbase were studied using the MP2/6-311++G**//B3LYP/6-31+G* approach. The thermal effects and activation barriers to individual reaction stages were evaluated. It was shown that stereoscpecificity of ketone vinylation with PhC≡CH is due to the possibility of isomerization of both carbanion intermediates and enolate anions originating from the final β,γ-unsaturated ketones. The calculated activation energies of the vinylation of substituted ketones are in good agreement with the experimentally observed differences in their reactivity with respect to the addition of phenylacetylene.

We conducted a detailed imaging study of transplanted Guerin’s carcinoma in rats during treatment with magnetic nanotherapy. We show that treatment with magneto-mechano-chemically synthesized magnetic nanocomplexes based on Fe3O4 nanoparticles conjugated with the antitumor agent doxorubicin and followed by irradiation with local electromagnetic irradiation resulted in a better outcome than treatment with conventional doxorubicin or treatment with magnetic nanocomplexes without electromagnetic irradiation. Analysis of magnetic resonance images obtained over time showed that the application of local electromagnetic irradiation did not alter the position of magnetic nanocomplexes in the tumor. B-mode sonography demonstrated that injection of magnetic nanocomplexes into the tumor and subsequent electromagnetic irradiation resulted in increased echogenicity throughout the tumor, which is characteristic of increased blood perfusion. Color Doppler ultrasound imaging showed that the largest decrease of tumor vessel area occurred after injection of magnetic nanocomplex and application of local electromagnetic irradiation. Elastography performed on a diagnostic ultrasound system showed that the injection of magnetic nanocomplexes in tumors increased Young’s modulus for Guerin’s carcinoma compared to tumors not treated with nanoparticles. These results suggest that a theranostics approach-combination MRI together with ultrasound elastography during treatment of tumor may provide a useful method to monitor the effectiveness treatment of cancer patients during magnetic nanotherapy.

The paper aims to compare zeta potentials, magnetic properties, electron spin resonance, photoluminescence (PL) spectra and antitumor effect of magneto-mechano-chemically synthesized magneto-sensitive nanocomplexes loaded with the anticancer drug doxorubicin (DOXO) during nanotherapy of Walker-256 carcinosarcoma carried out by a magnetic resonance system. Diamagnetic DOXO acquired the properties of a paramagnetic substance after synthesis. MNC comprising superparamagnetic nanoparticles (NP) and DOXO had different g-factors, zeta potentials, a lower saturation magnetic moment, area of the hysteresis loop, and a higher coercivity compared to similar MNC with ferromagnetic NP. The main PL peak of MNC spectrum was defined by DOXO at 598 nm. MNC composed of superparamagnetic NP and DOXO showed a lower standard deviation of the normal PL spectral distribution than MNC based on ferromagnetic NP in relation to conventional DOXO. MNC containing superparamagnetic NP responded to resonance conditions leading to a more pronounced antitumor effect compared to MNC with ferromagnetic NP in the course of magnetic nanotherapy for Walker-256 carcinosarcoma bearing animals (temperature inside the tumor did not exceed 40 °C). Therefore, these findings are associated with differences in chemotherapeutic effect between MNC due to a different surface charge and conformational changes in DOXO molecules during its magnetoelectric interaction with single- and multidomain NP.

Tumour hypoxia leads to radio and chemotherapy resistance among cancer patients. The aim of this paper is to formulate a hypothesis on the heterogeneity of hypoxia in solid tumours. Tumour vasculature is known to be significantly variable. The great structural and functional abnormalities of tumour microcirculation cause spatial and temporal heterogeneity in its perfusion. Tumours have constantly been under the influence of pulsatile blood perfusion with variable pressure that initiates inhomogeneous erythrocyte deformation and following impact on oxygen disorder release from red blood cells into plasma within the blood vessel. Furthermore, stochastically released oxygen in tumour vessel, plasma and interstitial fluid may lead to heterogeneity of hypoxia. Under the influence of increased heterogeneity of hemodynamic force, the oxygen molecules dissolved in blood plasma are inclined to form nanobubbles (NBs) in tumour vessels. Considering the fact that tumour interstitial fluid pressure is increased compared to normal tissues, we assume that oxygen NBs may burst under the impact of shear stress. During the course of mechanochemical reaction, when a nanobubble (NB) bursts, both reactive oxygen species and ions form in various charged states. In consequence of a chain reaction, free radical oxygen molecules bind to proteins and lipids, thus reducing oxygen molecules in a chaotic manner within the tumour. The proposed hypothesis should be used as a methodical approach based on the simultaneous ultrasound imaging diagnostic techniques and therapy, regarding the mechanochemical effect on NB conglomerates with drugs in the tumour.

An efficient construction of two non-classical families of orthogonal polynomials is presented in the paper. The so-called half-range Chebyshev polynomials of the first and second kinds were first introduced by Huybrechs in Huybrechs (2010) [5]. Some properties of these polynomials are also shown. Every integrable function can be represented as an infinite series of sines and cosines of these polynomials, the so-called half-range Chebyshev–Fourier (HCF) series. The second part of the paper is devoted to the efficient computation of derivatives and multiplication of the truncated HCF series, where two matrices are constructed for this purpose: the differentiation and the multiplication matrix.