Publications by authors named "Ryszard Maciejewski"

112 Publications

Status of CHEK2 and p53 in patients with early-onset and conventional gastric cancer.

Oncol Lett 2021 May 3;21(5):348. Epub 2021 Mar 3.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Gastric cancer (GC) is the fourth most common cause of cancer-associated death. Based on the age at diagnosis, GC is divided into early-onset GC (EOGC; ≤45 years) and conventional GC (CGC; >45 years). Mutations in the cell cycle checkpoint kinase 2 () and genes are associated with several types of cancer; however, their genetic defects in GC remain poorly understood. The aim of the present study was to determine the subcellular distribution of the CHEK2 protein and its redistribution following DNA damage, to improve the understanding of the DNA damage response. Genetic alterations and patterns of expression of CHEK2 and p53 proteins were investigated to identify potential biological markers and indicators of GC development. Additionally, the affected signaling pathways and their clinical importance in GC development and associated syndromes were investigated. A total of 196 GC samples (89 CGC and 107 EOGC samples) were used in the present study. DNA from 53 samples (18 CGC and 35 EOGC samples) was sequenced using targeted next-generation sequencing technology to identify and compare common and rare mutations associated with GC. Subsequently, the cytoplasmic and nuclear expression levels of CHEK2, phosphorylated (p)-CHEK2 at threonine 68 and p53 in GC tissues were determined via immunohistochemistry. Sequencing resulted in the identification of 63 single nucleotide polymorphisms (SNPs) in the gene amongst 5 different variants, and the intron variant c.319+379A>G was the most common SNP. In the gene, 57 different alterations were detected amongst 9 variant types, and the missense variant c.215C>G was the most common. Nuclear CHEK2 expression was high in both the EOGC and CGC subtypes. However, the prevalence of cytoplasmic CHEK2 expression (P<0.001) and nuclear p-CHEK2 expression (P=0.011) was significantly higher in CGC compared with in EOGC tissues. There was a statistically significant difference between high and low cytoplasmic CHEK2 expression in patients with p53-positive EOGC compared with in patients with p53-positive CGC (P=0.002). The present study was designed to determine the association between CHEK2 and p53 expression patterns in patients with EOGC and CGC, as well as genetic alterations in the and genes.
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http://dx.doi.org/10.3892/ol.2021.12609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967923PMC
May 2021

PD-L1 Expression Correlated with p53 Expression in Pediatric Glioblastoma Multiforme.

Brain Sci 2021 Feb 19;11(2). Epub 2021 Feb 19.

Laboratory of Virtual Man, Chair of Anatomy, Medical University of Lublin, 20-093 Lublin, Poland.

High-grade gliomas are infrequent in the pediatric population compared to adults, nevertheless, mortality and morbidity caused by malignant gliomas in this group of patients remain significant. PD-L1 and PD-1 Immune checkpoints (IC) molecules maintain immunological balance between activation and suppression. Eighteen patients with a histopathological diagnosis of pediatric glioblastoma multiforme (GBM, WHO IV) were studied. In total, PD-L1 expression was detected in 8 patients (44%). The molecular aspect of IC and immunotherapy targeted on PD-1/PD-L1 axis in pediatric population may be a promising adjuvant therapy in pediatric glioblastoma multiform treatment, however, this subject requires further investigation.
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http://dx.doi.org/10.3390/brainsci11020262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923158PMC
February 2021

COVID-19 in the autopsy room-requirements, safety, recommendations and pathological findings.

Forensic Sci Med Pathol 2021 03 4;17(1):101-113. Epub 2021 Jan 4.

Chair and Department of Forensic Medicine, Medical University of Lublin, 20-090, Lublin, Poland.

Modern technologies enable the exchange of information about the expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the continually increasing number of the coronavirus disease 2019 (COVID-19) cases almost in real time. The gravity of a current epidemiological situation is represented by the mortality rates, which are scrupulously updated daily. Performing autopsies on patients with either suspected or confirmed COVID-19 is of high importance since these might not only improve clinical management but also reduce the risk of SARS-CoV-2 infection expansion. The following paper aimed to present the most crucial aspects of SARS-CoV-2 infection from the point of view of forensic experts and pathologists, recommendations and safety precautions regarding autopsies, autopsy room requirements, possible techniques, examinations used for effective viral detection, recommendations regarding burials, and gross and microscopic pathological findings of the deceased who died due to SARS-CoV-2 infection. Autopsies remain the gold standard for determining the cause of death. Therefore, it would be beneficial to perform autopsies on patients with both suspected and confirmed COVID-19, especially those with coexisting comorbidities.
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http://dx.doi.org/10.1007/s12024-020-00341-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780078PMC
March 2021

Virulence Factors-Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment.

Cells 2020 Dec 25;10(1). Epub 2020 Dec 25.

Department of Anatomy, Medical University of Lublin, 20-400 Lublin, Poland.

Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by () is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.
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http://dx.doi.org/10.3390/cells10010027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824444PMC
December 2020

Beyond the Mind-Serum Trace Element Levels in Schizophrenic Patients: A Systematic Review.

Int J Mol Sci 2020 Dec 15;21(24). Epub 2020 Dec 15.

Chair and 1st Department of Psychiatry, Psychotherapy and Early Intervention, Medical University of Lublin, Gluska Street 1, 20-439 Lublin, Poland.

The alterations in serum trace element levels are common phenomena observed in patients with different psychiatric conditions such as schizophrenia, autism spectrum disorder, or major depressive disorder. The fluctuations in the trace element concentrations might act as potential diagnostic and prognostic biomarkers of many psychiatric and neurological disorders. This paper aimed to assess the alterations in serum trace element concentrations in patients with a diagnosed schizophrenia. The authors made a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 5009 articles identified through database searching, 59 of them were assessed for eligibility. Ultimately, 33 articles were included in the qualitative synthesis. This review includes the analysis of serum levels of the following trace elements: iron, nickel, molybdenum, phosphorus, lead, chromium, antimony, uranium, magnesium, aluminum, zinc, copper, selenium, calcium, and manganese. Currently, there is no consistency regarding serum trace element levels in schizophrenic patients. Thus, it cannot be considered as a reliable prognostic or diagnostic marker of schizophrenia. However, it can be assumed that altered concentrations of those elements are crucial regarding the onset and exaggeration of either psychotic or negative symptoms or cognitive dysfunctions.
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http://dx.doi.org/10.3390/ijms21249566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765526PMC
December 2020

Infiltrating Treg and Th17 Cells of the Prostate Hypertrophy Gland Associated with Infection.

Res Rep Urol 2020 30;12:593-597. Epub 2020 Nov 30.

Department of Normal Anatomy, Medical University of Lublin, Lublin, Poland.

Purpose: The aim of the study was to evaluate prostate cell infiltration by CD4(+)IL-17(+) and Treg cells in BPH and PCa patients depending on infection in the prostate gland.

Patients And Methods: Prostate fragments were collected from 54 patients with PCa and 34 patients with BPH. Rapid ID 32 was used to identify the bacteria. Cells were analyzed by flow cytometry BD FACSCanto II. Statistical analysis was performed using Statistica 7 software (TIBCO Software Inc, USA).

Results: was detected in 35% of patients with PCa and 41% of individuals with BPH. The infiltration of CD4(+)IL-17(+) and Treg cells was statistically significantly higher ( = 0.001) in patients with BPH and positive for . A statistically considerably higher ( = 0.001) infiltration of Treg cells in treated for PCa with infection was also demonstrated.

Conclusion: Prostatitis caused by may contribute to the development of BPH and PCa.
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http://dx.doi.org/10.2147/RRU.S284066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721300PMC
November 2020

Awareness of gastrointestinal tract malignancies among the population of Lublin province (Eastern Poland) - A cross-sectional study.

Ann Agric Environ Med 2020 Sep 20;27(3):469-475. Epub 2019 Dec 20.

Medical University, Lublin, Poland.

Introduction: Currently, malignancies are the most severe medical problems worldwide. Numerous, already known risk factors in carcinogenesis could be potentially avoided. Some cancer risk factors have been recognized and have become the targets of primary prophylaxis.

Objective: The aim of the study was to ascertain the state of knowledge about risk factors, primary prevention and early detection of malignancies of gastrointestinal tract (GIT) in the urban and rural population of the Lublin province in Eastern Poland.

Material And Methods: The study was cross-sectional. The originally designed questionnaire was applied to the group of 1,352 patients, representatives of both the rural and urban environments of the Lublin province during random appointments with their general practitioner (GP).

Results: The study showed low awareness of the issues connected with GIT malignancies within the studied group. The problem was particulary apparent in the rural population.

Conclusions: In order to raise general awareness of cancer, different means should be applied in urban and rural populations. GPs and the media were found to have the leading rols in the promotion of primary prevention.
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http://dx.doi.org/10.26444/aaem/113469DOI Listing
September 2020

Expression of cyclooxygenase-2 and mucin 1 in colorectal cancer.

Mol Clin Oncol 2020 Nov 20;13(5):52. Epub 2020 Aug 20.

Department of Surgical Oncology, Medical University of Lublin, Lublin 20-090, Poland.

In colorectal cancer (CRC), pathological factors that correlate with negative prognosis include, among others, overexpression of cyclooxygenase-2 (COX-2) and abundant expression of mucin 1 (MUC1). COX-2 overexpression may therefore be associated with MUC1 overexpression. The aim of the present study was to investigate the possible correlation between COX-2 and MUC1 expression and to assess the correlation between their individual expression and the clinicopathological features of patients, paying particular attention to survival. The following data was collected from the 170 patients with CRC included in the present study: Age, sex, tumour localization, disease stage and survival. Tumour samples were immunostained with antibodies against COX-2 and MUC1. Protein expression was scored, relative to reference staining, and correlated with the clinicopathological data of patients. The results revealed no correlation between the expressions of COX-2 and MUC1, or with any of the studied clinicopathological variables. In addition, the expression of the two proteins were not associated. Neither of the proteins demonstrated prognostic value for survival. The present study did not confirm a direct relationship between the expressions of COX-2 and MUC1, or between the expression of either protein and the clinicopathological features of patients, including survival.
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http://dx.doi.org/10.3892/mco.2020.2122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7453394PMC
November 2020

High-Throughput Sequencing of Gastric Cancer Patients: Unravelling Genetic Predispositions Towards an Early-Onset Subtype.

Cancers (Basel) 2020 Jul 21;12(7). Epub 2020 Jul 21.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Background: Gastric cancer is the fourth most common cause of cancer-related death. Currently, it is broadly accepted that the molecular complexity and heterogeneity of gastric cancer, both inter- and intra-tumor, display important barriers for finding specific biomarkers for the early detection and diagnosis of this malignancy. Early-onset gastric cancer is not as prevalent as conventional gastric carcinoma, but it is a preferable model for studying the genetic background, as young patients are less exposed to environmental factors, which influence cancer development.

Aim: The main objective of this study was to reveal age-dependent genotypic characteristics of gastric cancer subtypes, as well as conduct mutation profiling for the most frequent alterations in gastric cancer development, using targeted next-generation sequencing technology.

Patients And Methods: The study group included 53 patients, consisting of 18 patients with conventional gastric cancer and 35 with an early-onset subtype. The DNA of all index cases was used for next-generation sequencing, employing a panel of 94 genes and 284 single nucleotide polymorphisms (SNPs) (TruSight Cancer Panel, Illumina), which is characteristic for common and rare types of cancer.

Results: From among the 53 samples processed for sequencing, we were able to identify seven candidate genes (, and ) and nine variants among them: one splice_acceptor, four synonymous, and four missense variants. These were selected for the age-dependent differentiation of gastric cancer subtypes. We found four variants with C-Score ≥ 10, as 10% of the most deleterious substitutions: rs1800862 (), rs10138997 (), rs2230009 (), and rs2959656 (). We identified 36 different variants, among 24 different genes, which were the most frequent genetic alterations among study subjects. We found 16 different variants among the genes that were present in 100% of the total cohort: (rs2746462), (rs1670283), (rs2958057), (rs4925828; rs11342077, rs398010167; rs2721190), (rs326212), (rs540012), (rs4930199), (rs659243), (rs1169305), (rs206075; rs169547), (rs9514066; rs9514067), and (rs7183618).

Conclusions: The technology of next-generation sequencing is a useful tool for studying the development and progression of gastric carcinoma in a high-throughput way. Our study revealed that early-onset gastric cancer has a different mutation frequency profile in certain genes compared to conventional subtype.
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http://dx.doi.org/10.3390/cancers12071981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409326PMC
July 2020

Magnesium, Calcium, Potassium, Sodium, Phosphorus, Selenium, Zinc, and Chromium Levels in Alcohol Use Disorder: A Review.

J Clin Med 2020 Jun 18;9(6). Epub 2020 Jun 18.

Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Macronutrients and trace elements are important components of living tissues that have different metabolic properties and functions. Trace elements participate in the regulation of immunity through humoral and cellular mechanisms, nerve conduction, muscle spasms, membrane potential regulation as well as mitochondrial activity and enzymatic reactions. Excessive alcohol consumption disrupts the concentrations of crucial trace elements, also increasing the risk of enhanced oxidative stress and alcohol-related liver diseases. In this review, we present the status of selected macroelements and trace elements in the serum and plasma of people chronically consuming alcohol. Such knowledge helps to understand the mechanisms of chronic alcohol-use disorder and to progress and prevent withdrawal effects, also improving treatment strategies.
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http://dx.doi.org/10.3390/jcm9061901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357092PMC
June 2020

Neuroanatomical Changes in Leber's Hereditary Optic Neuropathy: Clinical Application of 7T MRI Submillimeter Morphometry.

Brain Sci 2020 Jun 9;10(6). Epub 2020 Jun 9.

Laboratory of Virtual Man, Medical University of Lublin, 20-400 Lublin, Poland.

Leber's hereditary optic neuropathy (LHON) is one of the mitochondrial diseases that causes loss of central vision, progressive impairment and subsequent degeneration of retinal ganglion cells (RGCs). In recent years, diffusion tensor imaging (DTI) studies have revealed structural abnormalities in visual white matter tracts, such as the optic tract, and optic radiation. However, it is still unclear if the disease alters only some parts of the white matter architecture or whether the changes also affect other subcortical areas of the brain. This study aimed to improve our understanding of morphometric changes in subcortical brain areas and their associations with the clinical picture in LHON by the application of a submillimeter surface-based analysis approach to the ultra-high-field 7T magnetic resonance imaging data. To meet these goals, fifteen LHON patients and fifteen age-matched healthy subjects were examined. For all individuals, quantitative analysis of the morphometric results was performed. Furthermore, morphometric characteristics which differentiated the groups were correlated with variables covering selected aspects of the LHON clinical picture. Compared to healthy controls (HC), LHON carriers showed significantly lower volume of both palladiums (left = 0.023; right = 0.018), the right accumbens area ( = 0.007) and the optic chiasm ( = 0.014). Additionally, LHON patients have significantly higher volume of both lateral ventricles (left = 0.034; right = 0.02), both temporal horns of the lateral ventricles (left = 0.016; right = 0.034), 3rd ventricle ( = 0.012) and 4th ventricle ( = 0.002). Correlation between volumetric results and clinical data showed that volume of both right and left lateral ventricles significantly and positively correlated with the duration of the illness (left = 0.841, = 0.002; right = 0.755, = 0.001) and the age of the LHON participants (left = 0.656, = 0.007; right = 0.691, = 0.004). The abnormalities in volume of the LHON patients' subcortical structures indicate that the disease can cause changes not only in the white matter areas constituting visual tracts, but also in the other subcortical brain structures. Furthermore, the correlation between those results and the illness duration suggests that the disease might have a neurodegenerative nature; however, to fully confirm this observation, longitudinal studies should be conducted.
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http://dx.doi.org/10.3390/brainsci10060359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348858PMC
June 2020

COVID-19: Specific and Non-Specific Clinical Manifestations and Symptoms: The Current State of Knowledge.

J Clin Med 2020 Jun 5;9(6). Epub 2020 Jun 5.

Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Coronavirus disease 2019 (COVID-19), due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become an epidemiological threat and a worldwide concern. SARS-CoV-2 has spread to 210 countries worldwide and more than 6,500,000 confirmed cases and 384,643 deaths have been reported, while the number of both confirmed and fatal cases is continually increasing. COVID-19 is a viral disease that can affect every age group-from infants to the elderly-resulting in a wide spectrum of various clinical manifestations. COVID-19 might present different degrees of severity-from mild or even asymptomatic carriers, even to fatal cases. The most common complications include pneumonia and acute respiratory distress syndrome. Fever, dry cough, muscle weakness, and chest pain are the most prevalent and typical symptoms of COVID-19. However, patients might also present atypical symptoms that can occur alone, which might indicate the possible SARS-CoV-2 infection. The aim of this paper is to review and summarize all of the findings regarding clinical manifestations of COVID-19 patients, which include respiratory, neurological, olfactory and gustatory, gastrointestinal, ophthalmic, dermatological, cardiac, and rheumatologic manifestations, as well as specific symptoms in pediatric patients.
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http://dx.doi.org/10.3390/jcm9061753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356953PMC
June 2020

Gastric Cancer: Epidemiology, Risk Factors, Classification, Genomic Characteristics and Treatment Strategies.

Int J Mol Sci 2020 Jun 4;21(11). Epub 2020 Jun 4.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Gastric cancer (GC) is one of the most common malignancies worldwide and it is the fourth leading cause of cancer-related death. GC is a multifactorial disease, where both environmental and genetic factors can have an impact on its occurrence and development. The incidence rate of GC rises progressively with age; the median age at diagnosis is 70 years. However, approximately 10% of gastric carcinomas are detected at the age of 45 or younger. Early-onset gastric cancer is a good model to study genetic alterations related to the carcinogenesis process, as young patients are less exposed to environmental carcinogens. Carcinogenesis is a multistage disease process specified by the progressive development of mutations and epigenetic alterations in the expression of various genes, which are responsible for the occurrence of the disease.
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http://dx.doi.org/10.3390/ijms21114012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312039PMC
June 2020

Recent Trends of microRNA Significance in Pediatric Population Glioblastoma and Current Knowledge of Micro RNA Function in Glioblastoma Multiforme.

Int J Mol Sci 2020 Apr 27;21(9). Epub 2020 Apr 27.

Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, Jaczewskiego 8, 20-954 Lublin, Poland.

Central nervous system tumors are a significant problem for modern medicine because of their location. The explanation of the importance of microRNA (miRNA) in the development of cancerous changes plays an important role in this respect. The first papers describing the presence of miRNA were published in the 1990s. The role of miRNA has been pointed out in many medical conditions such as kidney disease, diabetes, neurodegenerative disorder, arthritis and cancer. There are several miRNAs responsible for invasiveness, apoptosis, resistance to treatment, angiogenesis, proliferation and immunology, and many others. The research conducted in recent years analyzing this group of tumors has shown the important role of miRNA in the course of gliomagenesis. These particles seem to participate in many stages of the development of cancer processes, such as proliferation, angiogenesis, regulation of apoptosis or cell resistance to cytostatics.
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http://dx.doi.org/10.3390/ijms21093046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246719PMC
April 2020

The Evaluation of Optic Nerves Using 7 Tesla "Silent" Zero Echo Time Imaging in Patients with Leber's Hereditary Optic Neuropathy with or without Idebenone Treatment.

J Clin Med 2020 Apr 13;9(4). Epub 2020 Apr 13.

Department of Neuroimaging, King's College London, WC2R 2LS London, UK.

Magnetic Resonance Imaging (MRI) of the Optic Nerve is difficult due to the fine extended nature of the structure, strong local magnetic field distortions induced by anatomy, and large motion artefacts associated with eye movement. To address these problems we used a Zero Echo Time (ZTE) MRI sequence with an Adiabatic SPectral Inversion Recovery (ASPIR) fat suppression pulse which also imbues the images with Magnetisation Transfer contrast. We investigated an application of the sequence for imaging the optic nerve in subjects with Leber's hereditary optic neuropathy (LHON). Of particular note is the sequence's near-silent operation, which can enhance image quality of the optic nerve by reducing the occurrence of involuntary saccades induced during Magnetic Resonance (MR) scanning.
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http://dx.doi.org/10.3390/jcm9041112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230870PMC
April 2020

The function of miR-200 family in oxidative stress response evoked in cancer chemotherapy and radiotherapy.

Biomed Pharmacother 2020 May 25;125:110037. Epub 2020 Feb 25.

Department of Normal Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Since the beginning of the discovery of microRNAs (miRs), these molecules have attracted highly progressive attention due to their powerful regulatory roles in a broad spectrum of biological processes, including proliferation, differentiation, apoptosis and carcinogenesis. With regard to carcinogenesis, the miRs regulatory potency has been associated with cancer onset, progression, metastasis, diagnosis and therapeutic response. In this review we discuss the impact of miR-200 family on drug resistance development during anti-cancer therapy. Developing resistance to chemotherapeutic drugs as well as radiotherapy are major clinical obstacles in the successful therapeutic strategies to cancer treatment. Acquired cancer chemoresistance is a multifactorial phenomenon involving such factors as tumor type, tumor stage, cellular reactive oxygen species (ROS) level or ROS-responsive miRs profile. ROS level could influence the miRs expression level, which changes the cellular profile of the content of miRs. Such significant changes in the cellular miRs profile generate subsequent biological effects through the regulation of their target genes. This review outlines the interactions between ROS and miR-200 family in different kinds of cancers in response to chemotherapy.
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http://dx.doi.org/10.1016/j.biopha.2020.110037DOI Listing
May 2020

Micro RNA Molecules as Modulators of Treatment Resistance, Immune Checkpoints Controllers and Sensitive Biomarkers in Glioblastoma Multiforme.

Int J Mol Sci 2020 Feb 22;21(4). Epub 2020 Feb 22.

Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.

Based on genome sequencing, it is estimated that over 90% of genes stored in human genetic material are transcribed, but only 3% of them contain the information needed for the production of body proteins. This group also includes micro RNAs representing about 1%-3% of the human genome. Recent studies confirmed the hypothesis that targeting molecules called Immune Checkpoint (IC) open new opportunities to take control over glioblastoma multiforme (GBM). Detection of markers that indicate the presence of the cancer occupies a very important place in modern oncology. This function can be performed by both the cancer cells themselves as well as their components and other substances detected in the patients' bodies. Efforts have been made for many years to find a suitable marker useful in the diagnosis and monitoring of gliomas, including glioblastoma.
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http://dx.doi.org/10.3390/ijms21041507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073212PMC
February 2020

Influence of the Type of Delivery, Use of Oxytocin, and Maternal Age on Gene Expression in Stem Cells Derived from Wharton's Jelly within the Umbilical Cord.

Oxid Med Cell Longev 2019 14;2019:1027106. Epub 2019 Dec 14.

Department of Clinical Genetics, Medical University of Lublin, Poland.

The paper presents an evaluation of the gene expression in mesenchymal stem cells derived from Wharton's jelly within the umbilical cord, collected from 36 patients during labor. The study is the first one to show that the expression of in mesenchymal stem cells has been dependent on maternal age, birth order, route of delivery, and use of oxytocin. Our research proves that the gene expression in mesenchymal stem cells decreases with each subsequent pregnancy and delivery. Wharton's jelly stem cells obtained from younger women and during their first delivery, as well as patients treated with oxytocin, show higher gene expression when compared with the subsequent deliveries. This leads to a conclusion that they are characterized by a lower level of differentiation, which in turn results in their greater plasticity and greater proliferative potential. Probably, they are also clinically more useful.
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http://dx.doi.org/10.1155/2019/1027106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931016PMC
May 2020

The assessment of lenticulostriate arteries originating from middle cerebral artery using ultra high-field magnetic resonance time-of-flight angiography.

J Clin Neurosci 2019 Oct 19;68:262-265. Epub 2019 Jul 19.

Department of Anatomy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland; Ecotech-Complex, Maria Curie-Skłodowska University, Lublin, Poland.

Time-of-flight angiography (ToF) was presented for the first time by Suryan and used by Hinshaw et al. This protocol allows to visualize blood flow within the vessels in vivo without the contrast administration, which is possible due to the large magnitude of magnetization, received from the moving spins and small magnitude of magnetization received from the stationary spins. Fourteen participants (male:female = 7:7) were analyzed, who have never been diagnosed with any central nervous system disease as well as any cardiovascular, metabolic disease and have never had any trauma. Although, the gold standard of cerebral vessel analysis is still DSA, ultra high-field 3D ToF-MRA shows clearer picture of all LSAs and the branches of LSAs in comparison to poor in contrast DSA imaging. Ultra high-field time-of-flight MRA is a valuable method in visualizing small perforating arteries, which can be used in the future as a diagnostic tool for clinical practice. The diversity of LSAs morphometry is vast and may alter during aging, thus the clinical anatomy of those vessels should be further investigated in vivo.
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http://dx.doi.org/10.1016/j.jocn.2019.07.003DOI Listing
October 2019

Ethanol extracts of sp. regulate cyclooxygenase-2 and E-cadherin expression in gastric cancer MKN74 cell line and enhance doxorubicin toxicity.

Food Nutr Res 2019 25;63. Epub 2019 Jun 25.

Department of Anatomy, Medical University of Lublin, Lublin, Poland.

Background: Gastric cancer (GC) remains one of the leading causes of cancer-related death. Its aetiology is multifactorial, but the major risk factor is a high in salt diet. During gastric carcinogenesis, cadherin-1 (CDH1) down-expression and cyclooxygenase 2 (COX2) overexpression may be observed. The intensity of these alterations contributes to the GC invasion, its metastases and poor prognosis. As the diet plays a significant role in the aetiology of GC, it is reasonable to include the nutritional chemoprevention agents. One of the plant genus demonstrating chemoprotective properties is genus, which includes garlic. The relationship between CDH1 and COX2 in GC cells treated with species extract has never been evaluated.

Methods: In this study, the MKN28 and MKN74 GC cell lines were treated with ethanol extracts of L., Lam., L. (from Malaysia and Poland), Rendle and L. The cytotoxicity of the extracts and their influence on COX2 and CDH1 mRNA and protein expression were evaluated as well as their influence on doxorubicin's (DOX) efficacy - a drug that has been used in GC treatment.

Results: Among the tested species, ethanol extracts of L. (Poland and Malaysia), Rendle and L. influenced the levels of CDH1 and COX2, but only in the MKN74 cell line. Thus, it is possible that tumours with increased COX2 expression will be more susceptible to garlic treatment. Observed phenomenon was independent of extract's toxicity. In comparison to DOX, tested extracts were more toxic. Moreover, revealed synergistic effect with the drug.

Conclusion: In conclusion, the results indicate the potential application of genus to GC chemoprevention and treatment support through CDH restoration and COX2 downregulation. This issue needs further investigations as it might be used in clinics.
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http://dx.doi.org/10.29219/fnr.v63.3449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604903PMC
June 2019

Interactions between microRNA-200 family and Sestrin proteins in endometrial cancer cell lines and their significance to anoikis.

Mol Cell Biochem 2019 Sep 9;459(1-2):21-34. Epub 2019 May 9.

Department of Normal Anatomy, Medical University of Lublin, 20-090, Lublin, Poland.

In the present study, we intend to determine whether Sestrin proteins 1, 2, and 3 (SESN1-3) are targets of microRNA-200 family (miR-200) in endometrial cancer (EC) Ishikawa, AN3CA, KLE, and RL 95-2 cell lines and to investigate how these potential interactions influence anoikis resistance of EC cell lines. The luciferase reporter assay, qRT-PCR, and western blotting assays were used to verify whether SESN1-3 are direct targets of miR-200. Moreover, the anoikis assay and transient transfections of miR-200 mimics or inhibitors into EC cell lines were performed to evaluate the modulatory role of miR-200 and SESN proteins on anoikis resistance. We demonstrated that SESN2 protein is a direct target of mir-141 in KLE and RL-95-2 EC cell lines and the functional interaction of miR-141 and SESN2 protein has a downstream effect on anoikis resistance and SESN2 expression level in Ishikawa and AN3CA cell lines. Moreover, we have shown that SESN3 protein is a direct target of miR-200b, miR-200c, and miR-429 in Ishikawa, AN3CA, and KLE cell lines. Our results show that manipulation of miR-200b, miR-200c, and miR-429 expression patterns also has an influence on anoikis resistance in EC cell lines. In conclusion, we identified new interactions between miR-200 and the oxidative stress response SESN proteins that affect anoikis resistance in human EC cells.
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http://dx.doi.org/10.1007/s11010-019-03547-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679835PMC
September 2019

Increased Aluminum Content in Certain Brain Structures is Correlated with Higher Silicon Concentration in Alcoholic Use Disorder.

Molecules 2019 May 3;24(9). Epub 2019 May 3.

Department of Environmental Medicine, Poznan University of Medical Sciences, 61-701 Poznan, Poland.

Introduction: Alcohol overuse may be related to increased aluminum (Al) exposure, the brain accumulation of which contributes to dementia. However, some reports indicate that silicon (Si) may have a protective role over Al-induced toxicity. Still, no study has ever explored the brain content of Al and Si in alcoholic use disorder (AUD).

Materials And Methods: To fill this gap, the present study employed inductively coupled plasma optical emission spectrometry to investigate levels of Al and Si in 10 brain regions and in the liver of AUD patients ( = 31) and control ( = 32) post-mortem.

Results: Al content was detected only in AUD patients at mean ± SD total brain content of 1.59 ± 1.19 mg/kg, with the highest levels in the thalamus (4.05 ± 12.7 mg/kg, FTH), inferior longitudinal fasciculus (3.48 ± 9.67 mg/kg, ILF), insula (2.41 ± 4.10 mg/kg) and superior longitudinal fasciculus (1.08 ± 2.30 mg/kg). Si content displayed no difference between AUD and control, except for FTH. Positive inter-region correlations between the content of both elements were identified in the cingulate cortex, hippocampus, and ILF.

Conclusions: The findings of this study suggest that AUD patients may potentially be prone to Al-induced neurodegeneration in their brain-although this hypothesis requires further exploration.
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http://dx.doi.org/10.3390/molecules24091721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539762PMC
May 2019

CD44, TGM2 and EpCAM as novel plasma markers in endometrial cancer diagnosis.

BMC Cancer 2019 Apr 29;19(1):401. Epub 2019 Apr 29.

Laboratory of Biostructure, Chair of Human Anatomy, Medical University of Lublin, Lublin, Poland.

Background: Endometrial cancer (EC) is the most common malignancy of the female reproductive tract. Despite years of research, the accurate screening strategy is still not available in this disease and it is usually diagnosed only after the clinical signs are present. The recent technological advances in analytical methodologies enabled detection of multiple molecules in one, small sample of biological materials. Such approach was undertaken in the presented study.

Methods: Concentrations of aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), carbonic anhydrase IX (CA9), CD44, epithelial cell adhesion molecule (EpCAM), hepsin, kallikrein-6, mesothelin, midkine, neural cell adhesion molecule L1 (L1CAM), and transglutaminase 2 (TGM2) were measured using MAGPIX®System in plasma samples of 45 EC, 20 healthy controls and 11 patients with endometriosis.

Results: Significantly increased concentration in EC as compared to healthy controls were found in case of CD44 (p <  0.001), EpCAM (p = 0.033) and TGM2 (p <  0.001). EpCAM and mesothelin concentrations differed based on FIGO stages. Regression analysis revealed marker panels with high accuracy in detection of EC. The highest AUC 0.937 was attributed to the 3-marker panel of CD44/TGM2/EpCAM (84% sensitivity, 100% specificity), FIGO IA samples were discriminated from more advanced stages of EC with the mesothelin/grade 1 model featuring AUC of 0.911 (95.24% sensitivity, 78.26% specificity).

Conclusions: Novel plasma biomarkers presenting good accuracy in diagnosing EC were found with TGM2 reported for the first time as plasma marker. It was also revealed that endometriosis may share similarities in the pattern of markers alterations characteristic for EC.
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http://dx.doi.org/10.1186/s12885-019-5556-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6489287PMC
April 2019

Serum iron, Magnesium, Copper, and Manganese Levels in Alcoholism: A Systematic Review.

Molecules 2019 Apr 7;24(7). Epub 2019 Apr 7.

Chair and Department of Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

The aim of this paper was to review recent literature (from 2000 onwards) and summarize the newest findings on fluctuations in the concentration of some essential macro- and microelements in those patients with a history of chronic alcohol abuse. The focus was mainly on four elements which the authors found of particular interest: Iron, magnesium, copper, and manganese. After independently reviewing over 50 articles, the results were consistent with regard to iron and magnesium. On the other hand, data were limited, and in some cases contradictory, as far as copper and manganese were concerned. Iron overload and magnesium deficiency are two common results of an excessive and prolonged consumption of alcohol. An increase in the levels of iron can be seen both in the serum and within the cells, hepatocytes in particular. This is due to a number of factors: Increased ferritin levels, lower hepcidin levels, as well as some fluctuations in the concentration of the TfR receptor for transferrin, among others. Hypomagnesemia is universally observed among those suffering from alcoholism. Again, the causes for this are numerous and include malnutrition, drug abuse, respiratory alkalosis, and gastrointestinal problems, apart from the direct influence of excessive alcohol intake. Unfortunately, studies regarding the levels of both copper and manganese in the case of (alcoholic) liver disease are scarce and often contradictory. Still, the authors have attempted to summarize and give a thorough insight into the literature available, bearing in mind the difficulties involved in the studies. Frequent comorbidities and mutual relationships between the elements in question are just some of the complications in the study of this topic.
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http://dx.doi.org/10.3390/molecules24071361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480471PMC
April 2019

State of the art for gastric signet ring cell carcinoma: from classification, prognosis, and genomic characteristics to specified treatments.

Cancer Manag Res 2019 15;11:2151-2161. Epub 2019 Mar 15.

Department of Human Anatomy, Medical University of Lublin, Lublin, Poland,

Gastric cancer (GC) is responsible for 9% of cancer deaths worldwide. Over 950,000 new cases are diagnosed each year, and about 90% of them are in advanced stage, requiring chemotherapy. In Europe there has been research based on pre- and postoperative chemotherapy treatment, using 5-fluorouracil, epirubicin, cisplatin, capecitabine, and docetaxel. Chemotherapy significantly impairs the quality of life of patients; however, the final effects are not always satisfactory. There is scientific evidence that gastric mucus tumors and signet ring cell carcinomas have a pattern of specific signatures, that distinguish them from other gastric cancer subtypes, and may be associated with a poor response to systematic treatment. Signet ring cell carcinoma is less chemosensitive than others, and the increase in the percentage of signet ring cells correlates with resistance to chemotherapy. Perioperative chemotherapy in advanced signet ring cell carcinomas is an independent factor of poor prognosis and survival, which is explained by the toxicity of neoadjuvant treatment. Therefore, curative surgical resection enhanced by standardized lymphadenectomy remains the recommended gold standard in GC therapy. According to presented studies, early detection and aggressive treatments for this subtype of GC is a reasonable approach. This review paper is mostly addressed to physicians who are interested in updating to the state of the art concerning different subtypes of gastric carcinoma.
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http://dx.doi.org/10.2147/CMAR.S188622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421895PMC
March 2019

Analysis of Trace Elements in Human Brain: Its Aim, Methods, and Concentration Levels.

Front Chem 2019 5;7:115. Epub 2019 Mar 5.

Department of Anatomy, Medical University of Lublin, Lublin, Poland.

Trace elements play a crucial role in many biochemical processes, mainly as components of vitamins and enzymes. Although small amounts of metal ions have protective properties, excess metal levels result in oxidative injury, which is why metal ion homeostasis is crucial for the proper functioning of the brain. The changes of their level in the brain have been proven to be a risk factor for Alzheimer's, Parkinson's, and Huntington's diseases, as well as amyotrophic lateral sclerosis. Therefore, it is currently an important application of various analytical methods. This review covers the most important of them: inductively coupled ground mass spectrometry (ICP-MS), flame-induced atomic absorption spectrometry (FAAS), electrothermal atomic absorption spectrometry (GFAAS), optical emission spectrometry with excitation in inductively coupled plasma (ICP-OES), X-ray fluorescence spectrometry (XRF), and neutron activation analysis (NAA). Additionally, we present a summary of concentration values found by different research groups.
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http://dx.doi.org/10.3389/fchem.2019.00115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6411644PMC
March 2019

Madelung's disease - progressive, excessive, and symmetrical deposition of adipose tissue in the subcutaneous layer: case report and literature review.

Diabetes Metab Syndr Obes 2018 26;11:819-825. Epub 2018 Nov 26.

Department of Surgery with Trauma, Orthopaedic and Urological Subunit, Independent Public Health Care Center of the Ministry of Interior and Administration in Lublin, Lublin, Poland,

Madelung's disease is a rare disorder described for the first time in the year 1846 by Brodie. It is characterized by the occurrence of progressive, excessive, and symmetrical deposits of adipose tissue in the subcutaneous layer. Most often, these changes concern the neck, the nape of the neck, arms, and upper back, giving the patients a specific, pseudoathletic appearance. Madelung's disease is also known as multiple symmetrical lipomatosis, benign symmetrical lipomatosis, and Launois-Bensaude syndrome. The most commonly affected ones are men who drink alcohol in excessive amounts. The fat masses emerging in the course of the disease are painless but can lead to adverse repercussions. Patients may experience dysphagia, dysphonia, difficulty in breathing, and limited mobility of the neck. The reasons for the willingness to take up treatment are also often esthetic reasons. The disease is usually accompanied by numerous metabolic disorders. The etiology of the disease has not been sufficiently explained so far, which creates diagnostic and therapeutic difficulties. Currently used treatment is limited to surgical resection of the resulting lesions or liposuction. Unfortunately, the effectiveness of these activities is limited. Most patients experience recurrence after treatment. This paper discusses the essence of Madelung's disease, numerous aspects of etiology, the manner of diagnosis, and treatment based on current literature data.
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http://dx.doi.org/10.2147/DMSO.S181154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263218PMC
November 2018

associated factors in the development of gastric cancer with special reference to the early-onset subtype.

Oncotarget 2018 Jul 24;9(57):31146-31162. Epub 2018 Jul 24.

Department of Human Anatomy, Medical University of Lublin, Poland.

Nowadays, gastric cancer is one of the most common neoplasms and the fourth cause of cancer-related death on the world. Regarding the age at the diagnosis it is divided into early-onset gastric carcinoma (45 years or younger) and conventional gastric cancer (older than 45). Gastric carcinomas are rarely observed in young population and rely mostly on genetic factors, therefore provide the unique model to study genetic and environmental alternations. The latest research on early-onset gastric cancer are trying to explain molecular and genetic basis, because young patients are less exposed to environmental factors predisposing to cancer. In the general population, , has been particularly associated with intestinal subtype of gastric cancers. The significant association of infection in young patients with gastric cancers suggests that the has an etiologic role in both diffuse and intestinal subtypes of early-onset gastric cancers. In this paper we would like to ascertain the possible role of infection in the development of gastric carcinoma in young patients. The review summarizes recent literature on early-onset gastric cancers with special reference to infection.
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http://dx.doi.org/10.18632/oncotarget.25757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6089554PMC
July 2018

Neural stem cell therapy-Brief review.

Clin Neurol Neurosurg 2018 10 18;173:8-14. Epub 2018 Jul 18.

Department of Anatomy, Medical University of Lublin, Doktora Kazimierza Jaczewskiego 4, 20-400, Lublin, Poland.

Adult mammalian neural stem cells are unique because of their properties, such as differentiation capacity, self-renewal, quiescence, and also because they exist in specific niches, which are the subventricular zone (SVZ) and subgranular zone (SGZ) - the dentate gyrus of the hippocampus. SVZ is situated along the ependymal cell layer, dividing the ventricular area and subventricular zone. There are several sources of neural stem cells such as human embryonic stem cells, human fetal brain-derived neural stem/progenitor cells, human induced pluripotent stem cells, direct reprogrammed astrocytes. Stem cell sciences are a promising tool for research purposes as well as therapy. Induced pluripotent stem cells appear to be very useful for human neuron studies, allowing the creation of defined neuron populations, particularly for neurodevelopmental and neurodegenerative diseases as well as ischemic events. Neural stem cell sciences have a promising future in terms of stem cell therapy as well as research. There is, however, still a great need for further research to overcome obstacles.
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http://dx.doi.org/10.1016/j.clineuro.2018.07.013DOI Listing
October 2018

The Pattern of Signatures in Gastric Cancer Prognosis.

Int J Mol Sci 2018 Jun 4;19(6). Epub 2018 Jun 4.

Department of Human Anatomy, Medical University of Lublin, 20-090 Lublin, Poland.

Gastric cancer is one of the most common malignancies worldwide and it is a fourth leading cause of cancer-related death. Carcinogenesis is a multistage disease process specified by the gradual procurement of mutations and epigenetic alterations in the expression of different genes, which finally lead to the occurrence of a malignancy. These genes have diversified roles regarding cancer development. Intracellular pathways are assigned to the expression of different genes, signal transduction, cell-cycle supervision, genomic stability, DNA repair, and cell-fate destination, like apoptosis, senescence. Extracellular pathways embrace tumour invasion, metastasis, angiogenesis. Altered expression patterns, leading the different clinical responses. This review highlights the list of molecular biomarkers that can be used for prognostic purposes and provide information on the likely outcome of the cancer disease in an untreated individual.
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http://dx.doi.org/10.3390/ijms19061658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6032410PMC
June 2018