Colorectal cancer and dormant metastases:Put to sleep or destroy?

After reading the review by An et al“Biological factors driving colorectal cancer metastasis”,which covers the problem of the metastasis of colorectal cancer(CRC),I had a desire to discuss with readers one of the exciting problems associated with dormant metastases.Most deaths from CRCs are caused by metastases,which can be detected both at diagnosis of the primary tumor and several years or even decades after treatment.This is because tumor cells that enter the bloodstream can be destroyed by the immune system,cause metastatic growth,or remain dormant for a long time.Dormant tumor cells may not manifest themselves throughout a person’s life or,after some time and under appropriate conditions,may give rise to the growth of metastases.In this editorial,we will discuss the most important features of dormant metastases and the mechanisms of premetastatic niche formation,as well as factors that contribute to the activation of dormant metastases in CRCs.We will pay special attention to the possible mechanisms involved in the formation of circulating tumor cell complexes and the choice of therapeutic strategies that promote the dormancy or destruction of tumor cells in CRCs.

Different types of tumor microvessels in stageⅠ-ⅢA squamous cell lung cancer and their clinical significance

BACKGROUND Lung cancer(LC)is the leading cause of morbidity and mortality among malignant neoplasms.Improving the diagnosis and treatment of LC remains an urgent task of modern oncology.Previously,we established that in gastric,breast and cervical cancer,tumor microvessels(MVs)differ in morphology and have different prognostic significance.The connection between different types of tumor MVs and the progression of LC is not well understood.AIM To evaluate the morphological features and clinical significance of tumor MVs in lung squamous cell carcinoma(LUSC).METHODS A single-center retrospective cohort study examined medical records and archival paraffin blocks of 62 and 180 patients with stage I-IIIA LUSC in the training and main cohorts,respectively.All patients underwent radical surgery(R0)at the Orenburg Regional Cancer Clinic from May/20/2009 to December/14/2021.Tumor sections were routinely processed,and routine Mayer's hematoxylin and eosin staining and immunohistochemical staining for cluster of differentiation 34(CD34),podoplanin,Snail and hypoxia-inducible factor-1 alpha were performed.The morphological features of different types of tumor MVs,tumor parenchyma and stroma were studied according to clinicopathological characteristics and LUSC prognosis.Statistical analysis was performed using Statistica 10.0 software.Univariate and multivariate logistic regression analyses were performed to identify potential risk factors for LUSC metastasis to regional lymph nodes(RLNs)and disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with and without metastases in RLNs and those with and without disease recurrence.The effectiveness of the predictive models was assessed by the area under the curve.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.A value of P<0.05 was considered to indicate statistical significance.RESULTS Depending on the morphology,we classified tumor vessels into the following types:normal MVs,dilated capillaries(DCs),atypical DCs,DCs with weak expression of CD34,"contact-type"DCs,structures with partial endothelial linings,capillaries in the tumor solid component and lymphatic vessels in lymphoid and polymorphocellular infiltrates.We also evaluated the presence of loose,fine fibrous connective tissue(LFFCT)and retraction clefts in the tumor stroma,tumor spread into the alveolar air spaces(AASs)and fragmentation of the tumor solid component.According to multivariate analysis,the independent predictors of LUSC metastasis in RLNs were central tumor location(P<0.00001),the presence of retraction clefts(P=0.003),capillaries in the tumor solid component(P=0.023)and fragmentation in the tumor solid component(P=0.009),whereas the independent predictors of LUSC recurrence were tumor grade 3(G3)(P=0.001),stage N2(P=0.016),the presence of LFFCT in the tumor stroma(P<0.00001),fragmentation of the tumor solid component(P=0.0001),and the absence of tumor spread through the AASs(P=0.0083).CONCLUSION The results obtained confirm the correctness of our previously proposed classification of different types of tumor vessels and may contribute to improving the diagnosis and treatment of LUSC.

Predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa squamous cell lung cancer:A retrospective analysis

BACKGROUND Lung cancer(LC)is a global medical,social and economic problem and is one of the most common cancers and the leading cause of mortality from malignant neoplasms.LC is characterized by an aggressive course,and in the presence of disease recurrence risk factors,patients,even at an early stage,may be indicated for adjuvant therapy to improve survival.However,combined treatment does not always guarantee a favorable prognosis.In this regard,establishing predictors of LC recurrence is highly important both for determining the optimal treatment plan for the patients and for evaluating its effectiveness.AIM To establish predictors of disease recurrence after radical resection and adjuvant chemotherapy in patients with stage IIb-IIIa lung squamous cell carcinoma(LSCC).METHODS A retrospective case-control cohort study included 69 patients with LSCC who underwent radical surgery at the Orenburg Regional Clinical Oncology Center from 2009 to 2018.Postoperatively,all patients received adjuvant chemotherapy.Histological samples of the resected lung were stained with Mayer's hematoxylin and eosin and examined under a light microscope.Univariate and multivariate analyses were used to identify predictors associated with the risk of disease recurrence.Receiver operating characteristic curves were constructed to discriminate between patients with a high risk of disease recurrence and those with a low risk of disease recurrence.Survival was analyzed using the Kaplan-Meier method.The log-rank test was used to compare survival curves between patient subgroups.Differences were considered to be significant at P<0.05.RESULTS The following predictors of a high risk of disease recurrence in patients with stage IIb-IIa LSCC were established:a low degree of tumor differentiation[odds ratio(OR)=7.94,95%CI=1.08-135.81,P=0.049];metastases in regional lymph nodes(OR=5.67,95%CI=1.09-36.54,P=0.048);the presence of loose,fine-fiber connective tissue in the tumor stroma(OR=21.70,95%CI=4.27-110.38,P=0.0002);and fragmentation of the tumor solid component(OR=2.53,95%CI=1.01-12.23,P=0.049).The area under the curve of the predictive model was 0.846(95%CI=0.73-0.96,P<0.0001).The sensitivity,accuracy and specificity of the method were 91.8%,86.9%and 75.0%,respectively.In the group of patients with a low risk of LSCC recurrence,the 1-,2-and 5-year disease-free survival(DFS)rates were 84.2%,84.2%and 75.8%,respectively,while in the group with a high risk of LSCC recurrence the DFS rates were 71.7%,40.1%and 8.2%,respectively(P<0.00001).Accordingly,in the first group of patients,the 1-,2-and 5-year overall survival(OS)rates were 94.7%,82.5%and 82.5%,respectively,while in the second group of patients,the OS rates were 89.8%,80.1%and 10.3%,respectively(P<0.00001).CONCLUSION The developed method allows us to identify a group of patients at high risk of disease recurrence and to adjust to ongoing treatment.

Helicobacter pylori in gastric cancer: Features of infection and their correlations with long-term results of treatment

BACKGROUND Helicobacter pylori(H.pylori)is a spiral-shaped bacterium responsible for the development of chronic gastritis,gastric ulcer,gastric cancer(GC),and MALTlymphoma of the stomach.H.pylori can be present in the gastric mucosa(GM)in both spiral and coccoid forms.However,it is not known whether the severity of GM contamination by various vegetative forms of H.pylori is associated with clinical and morphological characteristics and long-term results of GC treatment.AIM To establish the features of H.pylori infection in patients with GC and their correlations with clinical and morphological characteristics of diseases and long-term results of treatment.METHODS Of 109 patients with GC were included in a prospective cohort study.H.pylori in the GM and tumor was determined by rapid urease test and by immunohistochemically using the antibody to H.pylori.The results obtained were compared with the clinical and morphological characteristics and prognosis of GC.Statistical analysis was performed using the Statistica 10.0 software.RESULTS H.pylori was detected in the adjacent to the tumor GM in 84.5%of cases,of which a high degree of contamination was noted in 50.4%of the samples.Coccoid forms of H.pylori were detected in 93.4%of infected patients,and only coccoid-in 68.9%.It was found that a high degree of GM contamination by the coccoid forms of H.pylori was observed significantly more often in diffuse type of GC(P=0.024),in poorly differentiated GC(P=0.011),in stage T3-4(P=0.04)and in N1(P=0.011).In cases of moderate and marked concentrations of H.pylori in GM,a decrease in 10-year relapse free and overall survival from 55.6%to 26.3%was observed(P=0.02 and P=0.07,respectively).The relationship between the severity of the GM contamination by the spiral-shaped forms of H.pylori and the clinical and morphological characteristics and prognosis of GC was not revealed.CONCLUSION The data obtained indicates that H.pylori may be associated not only with induction but also with the progression of GC.

Microbiota of the gastrointestinal tract: Friend or foe?

The gut microbiota is currently considered an external organ of the human body that provides important mechanisms of metabolic regulation and protection.The gut microbiota encodes over 3 million genes,which is approximately 150 times more than the total number of genes present in the human genome.Changes in the qualitative and quantitative composition of the microbiome lead to disruption in the synthesis of key bacterial metabolites,changes in intestinal barrier function,and inflammation and can cause the development of a wide variety of diseases,such as diabetes,obesity,gastrointestinal disorders,cardiovascular issues,neurological disorders and oncological concerns.In this review,I consider issues related to the role of the microbiome in the regulation of intestinal barrier function,its influence on physiological and pathological processes occurring in the body,and potential new therapeutic strategies aimed at restoring the gut microbiome.Herewith,it is important to understand that the gut microbiota and human body should be considered as a single biological system,where change of one element will inevitably affect its other components.Thus,the study of the impact of the intestinal microbiota on health should be considered only taking into account numerous factors,the role of which has not yet been fully elucidated.

Genetic heterogeneity of colorectal cancer and the microbiome

In 2020,the International Agency for Research on Cancer and the World Health Organization's GLOBOCAN database ranked colorectal cancer(CRC)as the third most common cancer in the world.Most cases of CRC(>95%)are sporadic and develop from colorectal polyps that can progress to intramucosal carcinoma and CRC.Increasing evidence is accumulating that the gut microbiota can play a key role in the initiation and progression of CRC,as well as in the treatment of CRC,acting as an important metabolic and immunological regulator.Factors that may determine the microbiota role in CRC carcinogenesis include inflammation,changes in intestinal stem cell function,impact of bacterial metabolites on gut mucosa,accumulation of genetic mutations and other factors.In this review,I discuss the major mechanisms of the development of sporadic CRC,provide detailed characteristics of the bacteria that are most often associated with CRC,and analyze the role of the microbiome and microbial metabolites in inflammation initiation,activation of proliferative activity in intestinal epithelial and stem cells,and the development of genetic and epigenetic changes in CRC.I consider longterm studies in this direction to be very important,as they open up new opportunities for the treatment and prevention of CRC.

Drying Drop Technology as a Possible Tool for Detection Leukemia and Tuberculosis in Cattle

Usual response of organism to viral or bacterial invasion represents antibodies production, qualitative and quantitative changes in composition of biological fluids. These changes influence conformation and surface characteristics of macromolecules (proteins), which become apparent in sessile drying drops, when they form aggregates due to salting-out effect and sediment. The bottom adsorption layers change their adhesive and viscoelastic properties in time depending on fluid composition and structure. The aim of this study was verification the idea of using this phenomenon in rapid vet diagnostics. Milk, blood and serum samples of 183 cows were tested using Drop Drying Technology (DDT). A drop of tested fluid dried on a polished quartz plate, oscillated with constant frequency—60 kHz. Mechanical properties of the drop changed during drying, influenced the electrical conductivity of the quartz plate. This signal was converted to the Acoustical- Mechanical Impedance (AMI) and displayed as a curve in coordinates AMI vs. Time. Shape of the AMI curve reflected this dynamics, and was used as a target for quantitative comparison between control and infected animals. Frequency analysis of the estimated parameters of the curves was performed using features of the Excel program. Powerful method of artificial neural network processing of the experimental data was also tested in this work as a possible tool for future development. Significant differences between control, Bovine leucosis virus positive (BLV+) and Bovine tuberculin positive (BTub+) cattle groups were obtained using all biological fluids—blood, serum and milk. We fixed also a season shift of the data, but distinction between groups still remained. In serum and milk some features of the AMI curves were more stable, and retained diagnostic properties when combined winter and spring databases. Further development of DDT is proposed.

Change of photosensitizer fluorescence at its diffusion in viscous liquid flow

In this paper,the mathematical model of distribution of the injected compound in biological liquid flow has been described.It is considered that biological liquid contains a few phases such as water,peptides and cells.The injected compound(for example,photosensitizer)can interact with peptides and cells.At the time,viscosity of the biological liquid depends on pathology present in organism.The obtained distribution of the compound connects on changes of its fluorescence spectra which are registered during fluorescent diagnostics of tumors.It is obtained that the curves do not have monotonic nature.There is a sharp curves decline in the first few seconds after injection.Intensivity of curves rises after decreasing.It is especially pronounced for wavelength 590 nm and 580 nm(near the"transparency window"of biological tissues).Time of inflection point shifts from 8.4 s to 6.9 s for longer wavelength.However,difference between curves is little for di®erent viscosity means of the biological liquid.Thus,additional pathology present in organism does not impact to the results of in vivo biomedical investigations.

Issues of origin,morphology and clinical significance of tumor microvessels in gastric cancer

Gastric cancer(GC)remains a serious oncological problem,ranking third in the structure of mortality from malignant neoplasms.Improving treatment outcomes for this pathology largely depends on understanding the pathogenesis and biological characteristics of GC,including the identification and characterization of diagnostic,prognostic,predictive,and therapeutic biomarkers.It is known that the main cause of death from malignant neoplasms and GC,in particular,is tumor metastasis.Given that angiogenesis is a critical process for tumor growth and metastasis,it is now considered an important marker of disease prognosis and sensitivity to anticancer therapy.In the presented review,modern concepts of the mechanisms of tumor vessel formation and the peculiarities of their morphology are considered;data on numerous factors influencing the formation of tumor microvessels and their role in GC progression are summarized;and various approaches to the classification of tumor vessels,as well as the methods for assessing angiogenesis activity in a tumor,are highlighted.Here,results from studies on the prognostic and predictive significance of tumor microvessels in GC are also discussed,and a new classification of tumor microvessels in GC,based on their morphology and clinical significance,is proposed for consideration.

Features of structure of external layer of murine hair at different stages of malignant tumor development

In the paper,the results of experimental investigations on the diferences of wool structure ofhealthy mice and mice with malignant tumor(s)are represented.It is shown that destruction ofwool structure happens during pathology development.Quantity of cells of external wool layerand their thickness decrease when the tumor capsule enlarges.Difference is seen even when thetumor is small.The obtained results can be used to improve optical techniques of biomedicaldiagnostics of cancer diseases.

Copper Nanoparticles as Modulators of Apoptosis and Structural Changes in Tissues

Results of research on copper nanoparticles influence on index of readiness to apoptosis and structural changes of liver, spleen, kidney tissues as well as sensomotor cerebral cortex under copper multiple introductions into organism of animals are presented in the article. It is established that copper nanoparticles distribute in organs and tissues of animals and cause specific structural changes. The increase of copper nanoparticles in organism up to toxical threshold (maximum tolerated dose) results in dystrophy and tissue necrosis. Accurate expression enhancement of Caspase 3 in micro-gliocytes (brain macrophages) has been registered seven days after one-fold intramuscular introduction of copper nanoparticles (dose 2 mg/kg of animal body weight), in liver cells - three and seven days after three-fold intramuscular introduction of copper nanoparticles (total dose was 6 mg/kg of animal body weight), in proximal kidney tubules-three hours, one, three and seven days after three-fold intramuscular introduction of copper nanoparticles (with total dose 6 mg/kg of animal body weight), in spleen cells three hours, one, three and seven days after 12-fold intramuscular introduction (with total dose 24 mg/kg of animal body weight). Received data enables us to propose using index of cells readiness to apoptosis defined by Caspase 3 expression as a criterion for copper nanoparticles introduction safety assessment.

Texture of Rotary-Friction-Welded from Dissimilar Medium Carbon Steels

The purpose of the present study was to investigate the texture in dissimilar medium carbon steels welded by rotary friction technique. The Electron Backscatter Diffraction (EBSD) technique was the main technique used to investigate the effect of welding on grain size and grain crystallographic orientation in the welded joint. Moreover, the effect of isothermal heat treatment at 600°C on welded joint has been studied knowing that this annealing allows to decrease the residual stresses. EBSD results revealed different subzones in welded joint. The texture in the weld is essentially composed of three components: Goss {110} <001>, Rotated Cube {100} <110>, and Rotated Goss {110} <110> orientation. The heat treatments applied on welded material had a slight effect on texture and grain size.

Combined Action of Lysozymes of Fresh-Water Bivalve Mollusks and Antibacterial Preparations against Some Clinical Strains of Microorganisms

The aim of the present study was to determine the MICs using broth microdilution method and their combination effect by （minimum inhibitory concentrations） of selected antibiotic agents determination of FICindex （fractional inhibitory concentrations）. Lysozyme Anodonta cygnea was more active than Lysozyme Uniopictorum, especially against Gram-negative bacterias. Combination of Macropen and Lysozyme Unio pictorum has a synergistic effect, while a separation of these antibacterial agents was not active against some of the strains of microorganisms.

Use of nanoscale metals in poultry diet as a mineral feed additive

The research was aimed at studying the efficiency of a nanoscale alloy of copper(Cu) and zinc(Zn) to be used as a mineral additive for feeding broiler chickens,compared to inorganic and organic forms of these elements.Biochemical studies of the blood serum were performed using an automated analyzer.The mineral composition was determined by atomic emission and mass spectrometry(MS-ISP),The study was performed on broiler chickens of cross Smena 7(n=72) in the conditions of a vivarium.There were3 treatment groups with 24 chickens in each.Replacing the inorganic form of mineral supplements with the nanosized alloy resulted in a positive productive effect,with a tendency to increasing the content of serum protein.The nano scale form of metals improved(P <0.05) the activity of aminotransferases.At the same time,the liver micro structure of experimental groups is similar to that of the control.There was a moderate plethora and poor polymorphoncellular infiltration around the interlobular triads with a clear morphological orga nization of the stromal and parenchymal co mponents of the liver.However,the lack of oxidative stress was confirmed by the dynamics of catalase(CT),total superoxide dismutase(TSOD) and malondialdehyde(MDA) levels,and the concentrations of which did not exceed the reference level Replacing Cu and Zn sulfates with the nanoscale alloy(group 1) and organic form(group 2) of these elements in the diet of broiler chickens was accompanied by the increasing pool of these elements in the organisms at the end of the experiment.Copper was accumulated throughout the experiment in experimental group 1,compared to the reference,with the maximum difference in the liver of 36.5%(P ≤ 0.05),in the feathers 2.5 times(P ≤ 0.01).Assessment of the Zn level dynamics in the feathers revealed a well noticeable tendency to reducing its concentrations during the experiment in all groups.Against the background of feeding a nanoscale alloy,Zn concentration in the liver exceeded the reference by 66.8%(P ≤ 0.01) only at the end of the experiment.Thus,nanoscale forms of Cu and Zn have a cumulative effect,and may become an alternative to inorganic and organic forms of these elements in poultry nutrition.