Publications by authors named "Joanna Reszec"

72 Publications

Vimentin binds to SARS-CoV-2 spike protein and antibodies targeting extracellular vimentin block uptake of SARS-CoV-2 virus-like particles.

bioRxiv 2021 Jan 8. Epub 2021 Jan 8.

Infection of human cells by pathogens, including SARS-CoV-2, typically proceeds by cell surface binding to a crucial receptor. In the case of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2) has been identified as a necessary receptor, but not all ACE2-expressing cells are equally infected, suggesting that other extracellular factors are involved in host cell invasion by SARS-CoV-2. Vimentin is an intermediate filament protein that is increasingly recognized as being present on the extracellular surface of a subset of cell types, where it can bind to and facilitate pathogens' cellular uptake. Here, we present evidence that extracellular vimentin might act as a critical component of the SARS-CoV-2 spike protein-ACE2 complex in mediating SARS-CoV-2 cell entry. We demonstrate direct binding between vimentin and SARS-CoV-2 virus-like particles coated with the SARS-CoV-2 spike protein and show that antibodies against vimentin block SARS-CoV-2 pseudovirus infection of ACE2-expressing cell lines. Our results suggest new therapeutic strategies for preventing and slowing SARS-CoV-2 infection, focusing on targeting cell host surface vimentin.
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http://dx.doi.org/10.1101/2021.01.08.425793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805437PMC
January 2021

Expression of LIGHT/TNFSF14 and Its Receptors, HVEM and LTβR, Correlates with the Severity of Fibrosis in Lacrimal Sacs from Patients with Lacrimal Duct Obstruction.

Ophthalmol Ther 2021 Mar 13;10(1):63-74. Epub 2020 Nov 13.

Department of Otolaryngology, Medical University of Bialystok, Bialystok, Poland.

Introduction: Fibrosis is one of the factors contributing to the development of primary acquired lacrimal duct obstruction (LDO). LIGHT (homologous to lymphotoxins, exhibiting inducible expression and competing with herpes simplex virus glycoprotein D for herpes virus entry mediator [HVEM]), a receptor expressed by T lymphocytes, has recently emerged as a new regulator of connective tissue remodeling and fibrotic response. The purpose of this study was to evaluate the role of LIGHT in the pathogenesis of LDO through: (1) assessment of expression of LIGHT and its two receptors, HVEM and LTβR (lymphotoxin β receptor), and (2) investigation of potential relationships between expression of LIGHT and its receptors and clinical and histopathologic features.

Methods: Lacrimal sacs of 30 patients undergoing endoscopic dacryocystorhinostomy because of LDO were assessed intraoperatively and histopathologically with respect to inflammation and fibrosis. Expression of LIGHT, HVEM and LTβR was assessed by immunohistochemistry using specific antibodies and evaluated semiquantitatively using a four-grade scoring system.

Results: All investigated molecules, LIGHT/TNFSF14, HVEM and LTβR, were expressed in biopsies from all patients. The most prominent expression was seen within inflammatory infiltrates. Expression of LIGH, HVEM and LTβR correlated significantly with the intensity of fibrosis and duration of the disease. In multivariate analysis only LIGHT showed a significant relationship with fibrosis (β coefficient = 0.759, p = 0.02). There was no significant correlation between expression of any molecule and other demographic or clinical features.

Conclusion: We assume that LIGHT along with its receptors may be a factor contributing to fibrosis and synechiae formation in the lacrimal sac. This assumption needs to be proven in a future study in a group of patients who fail to improve after the first operation.
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http://dx.doi.org/10.1007/s40123-020-00320-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665092PMC
March 2021

Nanomechanics and Histopathology as Diagnostic Tools to Characterize Freshly Removed Human Brain Tumors.

Int J Nanomedicine 2020 6;15:7509-7521. Epub 2020 Oct 6.

Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Bialystok PL-15222, Poland.

Background: The tissue-mechanics environment plays a crucial role in human brain physiological development and the pathogenesis of different diseases, especially cancer. Assessment of alterations in brain mechanical  properties during cancer progression might provide important information about possible tissue abnormalities with clinical relevance.

Methods: With atomic force microscopy (AFM), the stiffness of freshly removed human brain tumor tissue was determined on various regions of the sample and compared to the stiffness of healthy human brain tissue that was removed during neurosurgery to gain access to tumor mass. An advantage of indentation measurement using AFM is the small volume of tissue required and high resolution at the single-cell level.

Results: Our results showed great heterogeneity of stiffness within metastatic cancer or primary high-grade gliomas compared to healthy tissue. That effect was not clearly visible in lower-grade tumors like meningioma.

Conclusion: Collected data indicate that AFM might serve as a diagnostic tool in the assessment of human brain tissue stiffness in the process of recognizing tumors.
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http://dx.doi.org/10.2147/IJN.S270147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547774PMC
November 2020

Immunohistochemical markers for eosinophilic esophagitis.

Scand J Gastroenterol 2020 Nov 8;55(11):1277-1283. Epub 2020 Oct 8.

Department of Pediatrics, Gastroenterology, Hepatology, Nutrition and Allergology, Medical University of Bialystok, Bialystok, Poland.

Background And Aims: Eosinophilic esophagitis (EoE) is a chronic, local immune-mediated esophageal disease with eosinophil-dominated inflammation. The incidence of the disease is rapidly increasing in both children and adults. The pathogenesis of the disease is still not well understood. We present a review of the literature devoted to the EoE immunopathology, in particular the markers of inflammation and epithelial integrity, and their usefulness in disease monitoring and therapy.

Methods: We performed a systematic search of the MEDLINE/PubMed databases for studies to examine the use of immunohistochemistry as a diagnostic tool for EoE.

Results: The gold standard of EoE diagnosis requires multiple endoscopies with biopsies for histological assessment. The minimum number of eosinophils evaluated in hematoxylin-eosin staining to diagnose EoE is 15 per high-power field in at least one esophageal mucosa biopsy. However, in some cases, the count of eosinophils is not specific and insufficient as the only indicator. Recent works confirm the usefulness of assessment of some biomarkers in establishing the diagnosis and monitoring the treatment effects.

Conclusions: Immunohistochemistry seems to be a promising option not only in clinical recognition, but also in the selection and monitoring of treatment effects. However, these methods have not yet recommended for routine clinical use.
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http://dx.doi.org/10.1080/00365521.2020.1831053DOI Listing
November 2020

Expression of zinc transporter 8 in thyroid tissues from patients with immune and non-immune thyroid diseases.

Autoimmunity 2020 11 8;53(7):376-384. Epub 2020 Sep 8.

Department of Medical Patomorphology, Medical University of Bialystok, Bialystok, Poland.

Introduction: Recent studies have revealed the presence of zinc and the expression of zinc transporter (ZnT) family members in most endocrine cell types. It was demonstrated that ZnT family plays an important role in the synthesis and secretion of many hormones. Moreover, recently ZnT8 was described as a newly islet autoantigen in type 1 diabetes.

Materials And Methods: We studied the expression of ZnT8 transporter in thyroid tissues from patients with immune and non-immune thyroid diseases. The study was performed in thyroid tissues after thyroidectomy from patients with thyroid non-toxic nodular goitre (NTNG;  = 17, mean age 15.8 ± 2.2 years) and cases with Graves' disease ( = 20, mean age 15.6 ± 2.8). In our study we investigated the expression of ZnT8 in human thyroid tissues from patients with immune and non-immune thyroid diseases using immunohistochemistry, Western Blot as well as immunofluorescence analyses. To the best of our knowledge, this is the first investigation which identified ZnT8 protein expression in human thyroid tissues, moreover, confirmed by three different laboratory techniques. Expression of ZnT8 transporter was identified by immunohistochemistry in the thyroid tissues from paediatric patients with Graves' disease (on +++) and non-toxic nodular goitre (on ++). ZnT8 transporter expression was found both in thyroid follicular cells (within the cytoplasm and cytoplasmic membrane in follicular cells) and C cells (membrane-cytoplasmic reaction) in fluorescence. Predominant expression of ZnT8 in band 41 kDa in immune than in non-immune thyroid disorders may suggest potential role of ZnT8 as a new thyroid autoanitgen but it requires further study on a larger cohort.
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http://dx.doi.org/10.1080/08916934.2020.1815194DOI Listing
November 2020

Elevated plasma 20S proteasome chymotrypsin-like activity is correlated with IL-8 levels and associated with an increased risk of death in glial brain tumor patients.

PLoS One 2020 4;15(9):e0238406. Epub 2020 Sep 4.

Department of Biophysics, Medical University of Białystok, Białystok, Poland.

Introduction: In cancer treatment an attempt has been made to pharmacologically regulate the proteasome functions, thus the aim was to test whether 20S proteasome chymotrypsin-like (ChT-L) activity has a role in glial brain tumors. Furthermore, we analyzed the correlation between proteasome activity and IL-8, CCL2, NF-κB1 and NF-κB2 concentrations, which impact on brain tumors has already been indicated.

Methods: Plasma 20S proteasome ChT-L activity was assayed using the fluorogenic peptide substrate Suc-Leu-Leu-Val-Tyr-AMC in the presence of SDS. IL-8, CCL2, NF-κB1 and NF-κB2 concentration was analyzed with the use of ELISA method. Immunohistochemistry for IDH1-R132H was done on 5-microns-thick formalin-fixed, paraffin-embedded tumor sections with the use of antibody specific for the mutant IDH1-R132H protein. Labelled streptavidin biotin kit was used as a detection system.

Results: Brain tumor patients had statistically higher 20S proteasome ChT-L activity (0.649 U/mg) compared to non-tumoral individuals (0.430 U/mg). IDH1 wild-type patients had statistically higher 20S proteasome ChT-L activity (1.025 U/mg) compared to IDH1 mutants (0.549 U/mg). 20S proteasome ChT-L activity in brain tumor patients who died as the consequence of a tumor (0.649) in the following 2 years was statistically higher compared to brain tumor patients who lived (0.430 U/mg). In brain tumor patients the 20S proteasome ChT-L activity positively correlated with IL-8 concentration.

Conclusions: Elevated 20S proteasome ChT-L activity was related to the increased risk of death in glial brain tumor patients. A positive correlation between 20S proteasome ChT-L activity and IL-8 concentration may indicate the molecular mechanisms regulating glial tumor biology. Thus research on proteasomes may be important and should be carried out to verify if this protein complexes may represent a potential therapeutic target to limit brain tumor invasion.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238406PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473512PMC
October 2020

Recombinant Human Plasma Gelsolin Stimulates Phagocytosis while Diminishing Excessive Inflammatory Responses in Mice with Sepsis.

Int J Mol Sci 2020 Apr 7;21(7). Epub 2020 Apr 7.

Department of Medical Microbiology and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222 Bialystok, Poland.

Plasma gelsolin (pGSN) is a highly conserved abundant circulating protein, characterized by diverse immunomodulatory activities including macrophage activation and the ability to neutralize pro-inflammatory molecules produced by the host and pathogen. Using a murine model of Gram-negative sepsis initiated by the peritoneal instillation of Xen 5, we observed a decrease in the tissue uptake of IRDye800CW 2-deoxyglucose, an indicator of inflammation, and a decrease in bacterial growth from ascitic fluid in mice treated with intravenous recombinant human plasma gelsolin (pGSN) compared to the control vehicle. Pretreatment of the murine macrophage line RAW264.7 with pGSN, followed by addition of Xen 5, resulted in a dose-dependent increase in the proportion of macrophages with internalized bacteria. This increased uptake was less pronounced when cells were pretreated with pGSN and then centrifuged to remove unbound pGSN before addition of bacteria to macrophages. These observations suggest that recombinant plasma gelsolin can modulate the inflammatory response while at the same time augmenting host antibacterial activity.
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http://dx.doi.org/10.3390/ijms21072551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177774PMC
April 2020

Search of reference biomarkers reflecting orbital tissue remodeling in the course of Graves' orbitopathy.

Folia Histochem Cytobiol 2020 16;58(1):37-45. Epub 2020 Mar 16.

Department of Medical Pathomorphology, Cathedral of Biostructure, Medical University of Bialystok, Poland.

Introduction: Graves' orbitopathy (GO) is a complication in Graves' disease (GD) that causes disfigurement and sometimes blindness. The pathogenesis of GO remains unknown, while its symptoms demonstrate dependence between the thyroid gland and the orbit. The ongoing inflammatory process in retrobulbar tissue results in its remodeling characterized by increased volume of the orbital contents involving adipose tissue, with fibrosis and adipogenesis as predominant features. This study was aimed at the immunohistochemical verification of potential contribution and correlation between orbital expressions of IGF-1R, CD34, Foxp-3, PPAR-γ and CD4, CD68, TGF-β, FGF-β in severe and mild (long-lasting) GO.

Material And Methods: Forty-one orbital tissue specimens - 22 patients with severe GO, 9 patients with mild GO and 10 patients undergoing blepharoplasty as a control group - were processed by routine immunohistochemistry.

Results: Increased IGF-1R, CD34 and Foxp-3 expression was found in both severe and mild GO, yet a significant correlation between CD34 and CD4, CD68, TGF-β, FGF-β expressions was observed in long-lasting GO.

Conclusions: CD34 expression is proposed to be the marker of orbital tissue remodeling in the course of mild GO.
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http://dx.doi.org/10.5603/FHC.a2020.0003DOI Listing
November 2020

Thyroid carcinoma with atypical metastasis to the pituitary gland and unexpected postmortal diagnosis.

Endocrinol Diabetes Metab Case Rep 2020 Mar 13;2020. Epub 2020 Mar 13.

Departments of Endocrinology, Diabetology and Internal Medicine.

Summary: Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient's case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual.

Learning Points: The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes. Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy. This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.
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http://dx.doi.org/10.1530/EDM-19-0148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077587PMC
March 2020

Usefulness of Hybrid PET/MRI in Clinical Evaluation of Head and Neck Cancer Patients.

Cancers (Basel) 2020 Feb 22;12(2). Epub 2020 Feb 22.

Department of Medical Pathology, Medical University of Bialystok, 15-089 Bialystok, Poland.

(1) Background: The novel hybrid of positron emission tomography/magnetic resonance (PET/MR) examination has been introduced to clinical practice. The aim of our study was to evaluate PET/MR usefulness in preoperative staging of head and neck cancer (HNC) patients (pts); (2) Methods: Thirty eight pts underwent both computed tomography (CT) and PET/MR examination, of whom 21 pts underwent surgical treatment as first-line therapy and were further included in the present study. Postsurgical tissue material was subjected to routine histopathological (HP) examination with additional evaluation of p16, human papillomavirus (HPV), Epstein-Barr virus (EBV) and Ki67 status. Agreement of clinical and pathological T staging, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of CT and PET/MR in metastatic lymph nodes detection were defined. The verification of dependences between standardized uptake value (SUV value), tumor geometrical parameters, number of metastatic lymph nodes in PET/MR and CT, biochemical parameters, Ki67 index, p16, HPV and EBV status was made with statistical analysis of obtained results; (3) Results: PET/MR is characterized by better agreement in T staging, higher specificity, sensitivity, PPV and NPV of lymph nodes evaluation than CT imaging. Significant correlations were observed between SUVmax and maximal tumor diameter from PET/MR, between SUVmean and CT tumor volume, PET/MR tumor volume, maximal tumor diameter assessed in PET/MR. Other correlations were weak and insignificant; (4) Conclusions: Hybrid PET/MR imaging is useful in preoperative staging of HNC. Further studies are needed.
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http://dx.doi.org/10.3390/cancers12020511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072319PMC
February 2020

Histological evaluation of soft palate tissues in patients with sleep disordered breathing.

Otolaryngol Pol 2019 Dec;74(1):6-12

Klinika Otolaryngologii, Uniwersytet Medyczny w Białymstoku.

Introduction Sleep is a physiological state essential for proper functioning of the body. One of the reasons for sleep disorders is obstructive sleep apnea syndrome (OSAS).

Aim: The aim of this research is histological evaluation of the mucous membrane of the soft palate in patients affected by various forms of OSAS.

Material And Method: The studied group consisted of patients with sleep-related breathing disorder in the form of primary snoring or OSAS. People with chronic tonsillitis, without a history of sleep-related breathing disorders, were included in the comparative group. Fragments of the mucous membrane of the uvula (study group) and the glossopalatine arch (comparative group) were taken for histological examination during surgery. Using histological, histochemical and immunohistochemical methods, we assessed the presence and severity of inflammation (CD3, CD20, CD68), the structure of nerve fibers (S-100) and the size of blood vessels (CD34) in the examined tissue.

Results: Patients with OSAS developed a local inflammatory process in the oropharyngeal tissues (stronger expression of CD3, CD20, CD68 in people with OSAS). The exacerbation of the immunohistochemical reaction with CD3 correlated with the phase of OSAS. We found a higher degree of fibrosis and a higher expression of CD34 and S-100 receptors in subjects with OSAS compared to snoring patients and patients from the comparative group.

Discussion: Due to chronic tissue vibration, snoring most likely leads to damage to the nerve fibers in the soft palate, which can intensify episodes of shallow breathing during sleep and increase the occurrences of apnea.
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http://dx.doi.org/10.5604/01.3001.0013.6199DOI Listing
December 2019

Proline-Dependent Induction of Apoptosis in Oral Squamous Cell Carcinoma (OSCC)-The Effect of Celecoxib.

Cancers (Basel) 2020 Jan 6;12(1). Epub 2020 Jan 6.

Department of Pharmaceutical Analysis, Medical University of Bialystok, Mickiewicza 2D, 15-522 Białystok, Poland.

: Oral squamous cell carcinoma remains a significant worldwide public health challenge, associated with high morbidity and mortality. Treatment of this type of cancer lacks effective medication. Moreover, there are very few specific biomarkers that are useful in early diagnosis or treatment optimisation. Proline metabolism may prove to be of importance in the search for new treatment modalities. : To evaluate the significance of proline metabolism in the development of oral cancer, proline concentration was assessed in oral cancer tissue and normal oral mucosa. The results were compared to the clinical stage and histological grade of the tumours. Moreover, the expression of proteins involved in proline metabolism via proline dehydrogenase/oxidase (PRODH/POX, PPARγ, HIF1-α) was determined. In the next stage of the study, conducted on cell lines of tongue cancer treated with celecoxib, the aforementioned factors involved in proline metabolism were evaluated. Cellular viability and cell proliferation, as well as apoptosis, were also assessed. : Our research results indicate that a high intracellular proline concentration and expression of factors involved in its metabolism correlate with the clinical stage and histological grade of oral cancer. Moreover, we are the first researchers to demonstrate that celecoxib can affect proline metabolism, causing an increase in pro-apoptotic factors (PRODH/POX, PPARγ), reducing the expression of HIF-1α and activating apoptosis. : Proline metabolism, due to its involvement in the process of apoptosis, can be of great importance in anticancer therapy. It appears that celecoxib, which influences the PRODH/POX pathway, may be a promising therapeutic compound in oral cancer treatment.
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http://dx.doi.org/10.3390/cancers12010136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016823PMC
January 2020

Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA).

Cancers (Basel) 2019 Dec 21;12(1). Epub 2019 Dec 21.

Clinical Research Centre, Medical University of Bialystok, 15-276 Bialystok, Poland.

Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies consisting essentially of adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although the diagnosis and treatment of ADC and SCC have been greatly improved in recent decades, there is still an urgent need to identify accurate transcriptome profile associated with the histological subtypes of NSCLC. The present study aims to identify the key dysregulated pathways and genes involved in the development of lung ADC and SCC and to relate them with the clinical traits. The transcriptional changes between tumour and normal lung tissues were investigated by RNA-seq. Gene ontology (GO), canonical pathways analysis with the prediction of upstream regulators, and weighted gene co-expression network analysis (WGCNA) to identify co-expressed modules and hub genes were used to explore the biological functions of the identified dysregulated genes. It was indicated that specific gene signatures differed significantly between ADC and SCC related to the distinct pathways. Of identified modules, four and two modules were the most related to clinical features in ADC and SCC, respectively. , , , and in ADC, as well as and in SCC, are novel top hub genes in modules associated with tumour size, SUV, and recurrence-free survival. Our research provides a more effective understanding of the importance of biological pathways and the relationships between major genes in NSCLC in the perspective of searching for new molecular targets.
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http://dx.doi.org/10.3390/cancers12010037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7017323PMC
December 2019

Identification of protein changes in the blood plasma of lung cancer patients subjected to chemotherapy using a 2D-DIGE approach.

PLoS One 2019 17;14(10):e0223840. Epub 2019 Oct 17.

Department of Clinical Molecular Biology, Medical University of Bialystok, Bialystok, Poland.

A comparative analysis of blood samples (depleted of albumin and IgG) obtained from lung cancer patients before chemotherapy versus after a second cycle of chemotherapy was performed using two-dimensional difference gel electrophoresis (2D-DIGE). The control group consisted of eight patients with non-cancerous lung diseases, and the experimental group consisted of four adenocarcinoma (ADC) and four squamous cell carcinoma (SCC) patients. Analyses of gels revealed significant changes in proteins and/or their proteoforms between control patients and lung cancer patients, both before and after a second cycle of chemotherapy. Most of these proteins were related to inflammation, including acute phase proteins (APPs) such as forms of haptoglobin and transferrin, complement component C3, and clusterin. The variable expression of APPs can potentially be used for profiling lung cancer. The greatest changes observed after chemotherapy were in transferrin and serotransferrin, which likely reflect disturbances in iron turnover after chemotherapy-induced anaemia. Significant changes in plasma proteins between ADC and SCC patients were also revealed, suggesting use of plasma vitronectin as a potential marker of SCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0223840PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797170PMC
March 2020

The influence of leptin on the process of carcinogenesis.

Contemp Oncol (Pozn) 2019 13;23(2):63-68. Epub 2019 Jun 13.

Department of Medical Pathomorphology, Medical University of Bialystok, Poland.

Obesity is a new risk factor, to which more and more research is devoted, related to the development of cancer. Many studies of recent years have drawn attention to the role of adipose tissue as an important internal endocrine organ. In the adipose tissue proteins are produced, referred to by the common name as adipokines. In the case of obesity, the neoplasm cells are constantly stimulated by pro-inflammatory cytokines and adipokines, among which leptin dominates. The studies show that leptin can affect the cancer cells through numerous phenomena, e.g. inflammation, cell proliferation, suppression of apoptosis and angiogenesis. In this literature review we examined the role of leptin in the development of the individual cancers: breast cancer, colorectal cancer, prostate cancer, ovarian cancer, endometrial cancer and brain neoplasms: glioma and meningioma. However, leptin has very complicated mechanisms of action which require better understanding in certain types of cancer.
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http://dx.doi.org/10.5114/wo.2019.85877DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630388PMC
June 2019

Serum and cerebrospinal fluid Neudesin concentration and Neudesin Quotient as potential circulating biomarkers of a primary brain tumor.

BMC Cancer 2019 Apr 5;19(1):319. Epub 2019 Apr 5.

Department of Clinical Laboratory Diagnostics, Medical University of Bialystok, ul. Waszyngtona 15A, 15-269, Białystok, Poland.

Background: Despite the previously suggested role of Neudesin in tumorigenesis and its potential as a novel target for the treatment of cancers, its prognostic value has never been examined. Thus, the aim of the study was to evaluate Neudesin concentrations in primary brain tumor patients and make a comparison with non-tumoral individuals.

Methods: Cerebrospinal fluid (CSF) and serum Neudesin concentration was evaluated by means of the ELISA method.

Results: The total group of brain tumor patients had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.037). The meningeal tumor subgroup also had statistically lower serum Neudesin concentrations compared to the non-tumoral group (P = 0.012). The Astrocytic brain tumor subgroup had significantly higher CSF Neudesin concentrations compared to the non-tumoral group (P = 0.046). Neudesin Quotient (CSF concentration divided by serum concentration) in the astrocytic brain tumor subgroup was statistically higher compared to the non-tumoral group (P = 0.023). Males had statistically lower concentrations of the serum Neudesin compared to females (P = 0.047). Univariate linear regression analysis revealed that for women the serum Neudesin concentration was 1.53 times higher than for men. In the model of multivariate linear regression analysis, predictor variables influencing serum Neudesin concentrations included CSF Neudesin concentration and the Neudesin Quotient, if other model parameters are fixed. The developed model explains 82% of the variance in serum Neudesin concentration. Both linear regression models, univariate and multivariate, pointed to fewer factors with a potential to influence the Neudesin Quotient compared to serum Neudesin concentration.

Conclusions: In astrocytic brain tumor patients Neudesin concentrations within the cerebrospinal fluid are higher compared with non-tumoral individuals. Serum Neudesin concentration strongly correlates with its CSF level. In primary brain tumor patients serum Neudesin concentration is clearly gender-dependent. Linear regression models pointed to fewer factors that may influence the Neudesin Quotient value, which suggests it is a better biomarker of astrocytic brain tumors than serum and CSF Neudesin concentrations alone.
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http://dx.doi.org/10.1186/s12885-019-5525-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451205PMC
April 2019

Cysteinyl leukotriene 1 receptor expression in nasal polyps.

Otolaryngol Pol 2018 Oct;72(6):17-22

Uniwersytet Medyczny w Białymstoku Klinika Otolaryngologii.

Cysteinyl leukotrienes (CysLTs) have been implicated in the pathogenesis of chronic rhinosinusitis (CRS). This study was undertaken to better understand the role of CysLTs in the development of CRS through 1). assessment of the pattern of expression of CysLT1 receptor in nasal polyps from patients with CRS and 2). correlation of expression of CysLT1 receptor with clinical features. Expression of CysLT1 receptor was evaluated immunohistochemically in nasal polyps from 20 patients with CRS and nasal mucosa from 10 control subject undergoing plastic surgery of the nose. Patients with CRS showed significantly higher expression of CysLT1 receptor as compared with the control group (p<0.05). The expression of CysLT1 receptor in sub-epithelial inflammatory infiltrates tended to be higher in patients with CRS and allergy as compared with patients with CRS but without allergy (p=0.07). In particular, the expression of CysLT1 receptor in sub-epithelial inflammatory infiltrates was significantly greater in 3 patients with CRS and drug allergy as compared with patients with CRS but without drug allergy (p=0.03). Increased expression of CysLT1 receptor in inflamed mucosa of nasal polyps in patients with allergy might suggest particular role of CysLTs in the pathogenesis of nasal polyps in this group of patients.
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http://dx.doi.org/10.5604/01.3001.0012.5422DOI Listing
October 2018

Diagnosis of solitary extramedullary plasmacytoma located in the nasopharynx in a patient with acquired angioedema.

Postepy Dermatol Alergol 2018 Dec 13;35(6):636-637. Epub 2018 Nov 13.

Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.

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http://dx.doi.org/10.5114/ada.2018.77616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6320481PMC
December 2018

Increased expression of the TNF superfamily member LIGHT/TNFSF14 and its receptors (HVEM and LTßR) in patients with systemic sclerosis.

Rheumatology (Oxford) 2019 03;58(3):502-510

Department of Rheumatology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.

Objectives: This study aimed to assess the potential role of the TNF superfamily member lymphocyte T-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) in SSc through evaluation of: skin expression of LIGHT and its receptors, herpesvirus entry mediator and lymphotoxin ß-related receptor, and serum concentration of LIGHT in SSc patients.

Methods: Expression of LIGHT and its receptors was investigated by immunohistochemistry and evaluated semi-quantitatively in skin biopsies from 19 SSc patients and 9 healthy controls. Serum levels of LIGHT were measured using ELISA in 329 patients with SSc and 50 control subjects.

Results: Expression of LIGHT and both receptors was higher in SSc patients compared with controls (P < 0.05 for all comparisons). Patients with early SSc (⩽ 3 years from the first non-Raynaud's phenomenon symptom) showed higher expression of LIGHT and herpesvirus entry mediator compared with patients with longer disease duration (P < 0.05 for both comparisons). The mean serum concentration of LIGHT was significantly higher in SSc patients compared with the controls (P < 0.05). High serum concentration of LIGHT was associated with male sex, presence of digital ulcers, muscle involvement (defined by elevated serum creatine kinase levels), steroid treatment and lack of ACA. However, in multivariate regression analysis only presence of digital ulcers and creatine kinase elevation were independently associated with serum concentration of LIGHT.

Conclusion: These data provide the first evidence of overexpression of LIGHT and its receptors in SSc and suggest that the LIGHT axis might contribute to the pathogenesis of SSc. Increased serum concentrations of LIGHT seem to reflect vascular injury in SSc.
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http://dx.doi.org/10.1093/rheumatology/key348DOI Listing
March 2019

Whole genome sequencing puts forward hypotheses on metastasis evolution and therapy in colorectal cancer.

Nat Commun 2018 11 14;9(1):4782. Epub 2018 Nov 14.

Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University Heidelberg, 69120 Mannheim, Germany.

Incomplete understanding of the metastatic process hinders personalized therapy. Here we report the most comprehensive whole-genome study of colorectal metastases vs. matched primary tumors. 65% of somatic mutations originate from a common progenitor, with 15% being tumor- and 19% metastasis-specific, implicating a higher mutation rate in metastases. Tumor- and metastasis-specific mutations harbor elevated levels of BRCAness. We confirm multistage progression with new components ARHGEF7/ARHGEF33. Recurrently mutated non-coding elements include ncRNAs RP11-594N15.3, AC010091, SNHG14, 3' UTRs of FOXP2, DACH2, TRPM3, XKR4, ANO5, CBL, CBLB, the latter four potentially dual protagonists in metastasis and efferocytosis-/PD-L1 mediated immunosuppression. Actionable metastasis-specific lesions include FAT1, FGF1, BRCA2, KDR, and AKT2-, AKT3-, and PDGFRA-3' UTRs. Metastasis specific mutations are enriched in PI3K-Akt signaling, cell adhesion, ECM and hepatic stellate activation genes, suggesting genetic programs for site-specific colonization. Our results put forward hypotheses on tumor and metastasis evolution, and evidence for metastasis-specific events relevant for personalized therapy.
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http://dx.doi.org/10.1038/s41467-018-07041-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6235880PMC
November 2018

Low Grade Chondrosarcoma - Epidemiology, Diagnosis, Treatment.

Ortop Traumatol Rehabil 2018 Feb;20(1):65-70

Klinika Ortopedii i Traumatologii USK w Białymstoku, Polska, Zakład Patomorfologii Lekarskiej UM w Białymstoku, Polska.

The article describes epidemiology, clinical features and treatment strategy of chondrosarcoma with special regard to diagnostic and therapeutic difficulties in low grade chondrosarcomas. Chondrosarcomas account for 3.5-9% of primary bone tumors and approximately 30% of primary bone malignancies. They occur in the 4th to 7th decade of life, slightly more commonly in men. The most common locations are the pelvis, ribs, proximal femur and proximal humerus. Gradually increasing pain is the most common presenting symptom. Diagnosis must be based on clinical, radiological (conventional radiology, computed tomography, magnetic resonance imaging) and histopathological features. Treatment of the tumor is based on complete removal according to the principles of oncological asepsis. Lung metastases may develop and are associated with a markedly poorer prognosis.
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http://dx.doi.org/10.5604/01.3001.0011.5879DOI Listing
February 2018

Blood bioactive sphingolipids in patients with advanced serous epithelial ovarian cancer - mass spectrometry analysis.

Arch Med Sci 2021 10;17(1):53-61. Epub 2018 Jul 10.

Department of Physiology, Medical University of Bialystok, Bialystok, Poland.

Introduction: Due to the lack of highly specific and sensitive methods for diagnosing ovarian cancer at advanced stages (according to the International Federation of Gynecology and Obstetrics (FIGO) classification stage III-IV), new noninvasive biomarkers are urgently needed. This study aims to investigate how the levels of plasma bioactive sphingolipids (ceramides, sphingosine-1-phosphate, sphingosine and sphinganine) are altered in serum, erythrocytes and platelets of patients with advanced serous ovarian cancer.

Material And Methods: A total of 135 patients with advanced serous ovarian cancer and 159 women with normal ovarian morphology were enrolled. Plasma levels of sphingosine, sphingosine-1-phosphate, sphinganine, ceramide C14:0-Cer, C16:0-Cer, C18:1-Cer, C18:0-Cer, C20:0-Cer, C22:0-Cer, C24:1-Cer and C24:0-Cer were assessed by LC/MS/MS.

Results: Plasma concentrations of C16-Cer, C18:1-Cer and C18-Cer were significantly higher in the advanced ovarian cancer group than in the control group (1.5-fold, = 0.021; 1.8-fold, = 0.036 and 1.5-fold, = 0.031, respectively). Plasma concentration of C18:1-Cer was significantly higher in erythrocytes of women with advanced serous cancer compared to the control group ( = 0.027). Plasma C16-Cer and C18:1-Cer levels and erythrocyte C18:1-Cer levels were able to distinguish patients with moderate/severe serous ovarian cancer from patients with mild ovarian cancer (AUC: 0.86, 0.898, 0.795, respectively). Plasma concentrations of C16, C18.1 and C18 significantly correlated with FIGO staging ( = 0.001, = 0.024 and = 0.005), and grading ( = 0.021, = 0.021 and = 0.033).

Conclusions: Plasma concentrations of C16, C18.1 and C18 correlated with the progression of ovarian cancer (FIGO staging and grading). Plasma levels of C16-Cer and C18:1-Cer and erythrocyte C18:1-Cer levels could be used to distinguish patients with advanced serous ovarian cancer.
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http://dx.doi.org/10.5114/aoms.2018.76996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811313PMC
July 2018

Comprehensive histopathological diagnostics of aggressive B-cell lymphomas based on the updated criteria of the World Health Organisation's 2017 classification.

Pol J Pathol 2018;69(1):1-19

Revision of the fourth edition of the World Health Organisation (WHO) Classification of Haematopoietic and Lymphatic Tissues, which was published in 2017, introduced important changes updating the biology, pathology, genetics, and clinical presentation of aggressive B-cell lymphomas. High grade B-cell lymphomas (HGBLs) replaced B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma, the new provisional entity Burkitt-like lymphoma with 11q aberration was identified, and some categories were upgraded, e.g. EBV-positive diffuse large B-cell lymphoma, not otherwise specified. Still the histopathological diagnostics is based on morphology and immunoprofile, but to define the HGBLs evaluation of MYC, BCL2, and BCL6 gene statuses is required. According to the presented WHO criteria, in the comprehensive histopathological diagnostics of aggressive B-cell lymphomas a highly specialised diagnostic team including a pathologist, a molecular biologist, a geneticist, a haematologist, and immunophenotyping technicians is needed.
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http://dx.doi.org/10.5114/pjp.2018.75332DOI Listing
July 2018

Frequent expression of somatostatin receptor 2a in olfactory neuroblastomas: a new and distinctive feature.

Hum Pathol 2018 09 25;79:144-150. Epub 2018 May 25.

Department of Pathology, Technische Universität München, München, Germany.

Olfactory neuroblastoma (ONB) is a malignant neuroendocrine neoplasm with a usually slow course, but with considerable recurrence rate. Many neuroendocrine tumors have shown good response to the treatment with somatostatin analogs and somatostatin radioreceptor therapy. In ONBs, there are scarce data on somatostatin-based treatment and the cellular expression of somatostatin receptors (SSTR), the prerequisite for binding and effect of somatostatin on normal and tumor cells. The aim of our study was to investigate the immunohistochemical expression of SSTR2A and SSTR5 in a cohort of 40 ONBs. In addition, tissue microarrays containing 40 high-grade sinonasal carcinomas as well as 6 sinonasal lymphomas, 3 rhabdomyosarcomas, and 3 Ewing sarcomas were evaluated. Volante system was applied for staining evaluation. Thirty cases (75%) were immunopositive for SSTR2A and 3 (7.5%) for SSTR5. Among the 30 SSTR2A-positive ONBs, 19 tumors (63.3%) scored 2+ and 11 (36.7%) scored 3+. All SSTR5-positive ONBs scored 2+. Neither sinonasal carcinomas nor sinonasal small round blue cell neoplasms expressed SSTR2A or SSTR5. The frequent expression of SSTR2A provides a rationale for radioreceptor diagnosis and therapy with SST analogs in ONBs. SSTR2A expression in ONBs is a helpful adjunct in the differential diagnosis of ONBs.
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http://dx.doi.org/10.1016/j.humpath.2018.05.013DOI Listing
September 2018

Review on Retinal Gliosis Illustrated with a Series of Massive Glioses and Focal Nodular Gliosis Cases in Regard to Potential Pitfalls of Ocular Reactive Tumor-like Lesions of this Type.

Folia Med (Plovdiv) 2018 Mar;60(1):30-38

Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland.

This paper presents a review on retinal gliosis illustrated by series of three cases of patients (a 39-year-old man and a 35-year-old woman with massive retinal gliosis (MRG) and a 51-year-old man with truly focal nodular gliosis of retina) with intraocular tumor-like masses and loss of vision, who recently suffered from painful inflammation of eyeball and who classically had a history of remote ocular trauma, onset of blindness early in lifetime or gradual but progressive loss of sight. The diagnosis of this pathological entity is given for the lesions that are composed of GFAP strongly positive, elongated, fusiform cells consistent with fibrillary astrocytes. As illustrated in cases from our pathological practice, PAS gave positive patchy disseminated reaction in form of cellular densely purplish granules in minority of cells representing glycogen storing. This feature could be consistent with PAS-positive Müller cells that also constitute retinal gliosis as one of cellular components of normal retina that is induced to reactive proliferation. Thus, the paper presents histological background and differential diagnosis of the entity.
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http://dx.doi.org/10.1515/folmed-2017-0061DOI Listing
March 2018

Radionegative Low Grade Chondrosarcoma in Distal Third of Femur. Case Study.

Ortop Traumatol Rehabil 2017 Dec;19(6):543-551

Uniwersytet Medyczny w Białymstoku / Medical University of Bialystok / Zakład Patomorfologii Lekarskiej / Division of Anatomical Pathology.

We present the case of a 43-year-old patient with a radionegative tumor of the distal third of the femur. Work-up following a knee injury without any abnormalities on x-ray was extended to include an MRI study, which revealed an osteolytic lesion in the distal third of the femur. Extended work-up including an open biopsy identified a low-grade chondrosarcoma. Considering the patient's clinical status and the diagnostic findings, tumour resection and placement of a resection knee endoprosthesis appeared to be the best solution. The clinical outcome was good.
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http://dx.doi.org/10.5604/01.3001.0010.8046DOI Listing
December 2017

Expression of N-cadherin and β-catenin in human meningioma in correlation with peritumoral edema.

Int J Neurosci 2018 Sep 18;128(9):805-810. Epub 2018 Jan 18.

c Department of Medical Pathomorphology , Medical University of Bialystok , Bialystok , Poland.

Objective: To analyze the expression of β-catenin and N-cadherin in large series of meningioma cases and to investigate their correlation with peritumoral brain edema (PTBE).

Materials And Methods: Study group consists of 154 patients diagnosed with intracranial meningioma divided into: low-grade (G1) and high-grade (G2 or G3) group. PTBE was graded into four groups (0, I, II, III) using Steinhoff classification. The expression of N-cadherin, β-catenin was analyzed and graded based on the positive ratio of immunoreactivity. The results were analyzed statistically.

Results: 104 cases were low-grade and 50 high-grade meningiomas. PTBE was observed in 103(66.8 %) cases: 57 grade I, 44 grade II and 2 grade III. Positive N-cadherin expression was found only in the membrane of the neoplastic cells in 50(48.1%) cases of low-grade, and in 34(68%) of high-grade group. In low-grade meningioma, β-catenin expression was observed within the cytoplasm and nucleus in 54(51.9%) cases. In high-grade meningiomas, β-catenin expression was observed in 33(66%) tumors only within the nucleus. N-cadherin expression was observed in 36 cases with PTBE grade I, 28 with grade II and 2 with grade III. β-catenin expression was observed in 40 cases with PTBE grade I, 24 with grade II and 2 with grade III. The results were statistically significant.

Conclusions: Significant N-cadherin expression especially in high-grade meningioma group was found. β-catenin expression was the most evident in the nucleus rather than in cytoplasm. The degree of PTBE correlated with the N-cadherin and β-catenin expression and was the most prominent in high-grade meningioma group.
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http://dx.doi.org/10.1080/00207454.2018.1424153DOI Listing
September 2018

Protective effect of cigarette smoke on the course of dextran sulfate sodium-induced colitis is accompanied by lymphocyte subpopulation changes in the blood and colon.

Int J Colorectal Dis 2017 Nov 16;32(11):1551-1559. Epub 2017 Aug 16.

Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, ul. M. Sklodowskiej-Curie 24a, 15-276, Bialystok, Poland.

Background: Cigarette smoke (CS) exerts protective effect against ulcerative colitis. The mechanism of this phenomenon remains unknown. One of the possible explanation by which CS exerts its anti-inflammatory action is modulation of immune system. Therefore, the aim of the study was to evaluate the effect of CS on the course of inflammation and subpopulations of lymphocytes in the blood and colon in mice with dextran sulfate sodium (DSS)-induced colitis.

Methods: C57BL6/cmdb mice were exposed to CS for 4 weeks. Colitis was induced with 3.5% DSS given for 10 days. Severity of colitis was determined by disease activity index (DAI), body weight changes, and macro- and microscopic characteristics of inflammation. Peripheral subpopulations of lymphocytes were assessed by flow cytometry (blood) or immunohistochemistry (colonic tissue).

Results: Mice treated with 3.5% DSS developed severe colitis with significantly decreased body weight, increased DAI, and macroscopic and histological features of colonic inflammation. These findings were diminished after concomitant exposure to CS. Mice exposed to DSS alone demonstrated significantly decreased percentage of total CD4 cells (73.1 vs. 52%, p = 0.0007), accompanied by increase of CD8 cells (18.4 vs. 39.5%, p = 0.0001). Concomitant CS exposure reversed inappropriate CD4/CD8 ratio both in the blood and colon and significantly increased B cell presence in the colon.

Conclusions: Our study has demonstrated that CS exposure decreases severity of DSS-induced colitis. This phenomenon was accompanied by changes in CD4/CD8 ratio and B cell level in the peripheral blood and colon. These mechanisms may be responsible for protective effect of smoking in ulcerative colitis.
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http://dx.doi.org/10.1007/s00384-017-2882-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5635083PMC
November 2017

Ultrastructural Characteristics of Rat Hepatic Oval Cells and Their Intercellular Contacts in the Model of Biliary Fibrosis: New Insights into Experimental Liver Fibrogenesis.

Gastroenterol Res Pract 2017 9;2017:2721547. Epub 2017 Jul 9.

Department of Pediatric Surgery, Medical University of Bialystok, Bialystok, Poland.

Purpose: Recently, it has been emphasized that hepatic progenitor/oval cells (HPCs) are significantly involved in liver fibrogenesis. We evaluated the multipotential population of HPCs by transmission electron microscope (TEM), including relations with adherent hepatic nonparenchymal cells (NPCs) in rats with biliary fibrosis induced by bile duct ligation (BDL).

Methods: The study used 6-week-old Wistar Crl: WI(Han) rats after BDL for 1, 6, and 8 weeks.

Results: Current ultrastructural analysis showed considerable proliferation of HPCs in experimental intensive biliary fibrosis. HPCs formed proliferating bile ductules and were scattered in periportal connective tissue. We distinguished 4 main types of HPCs: 0, I, II (bile duct-like cells; most common), and III (hepatocyte-like cells). We observed, very seldom presented in literature, cellular interactions between HPCs and adjacent NPCs, especially commonly found transitional hepatic stellate cells (T-HSCs) and Kupffer cells/macrophages. We showed the phenomenon of penetration of the basement membrane of proliferating bile ductules by cytoplasmic processes sent by T-HSCs and the formation of direct cell-cell contact with ductular epithelial cells related to HPCs.

Conclusions: HPC proliferation induced by BDL evidently promotes portal fibrogenesis. Better understanding of the complex cellular interactions between HPCs and adjacent NPCs, especially T-HSCs, may help develop antifibrotic therapies in the future.
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http://dx.doi.org/10.1155/2017/2721547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5523291PMC
July 2017

Systematic biobanking, novel imaging techniques, and advanced molecular analysis for precise tumor diagnosis and therapy: The Polish MOBIT project.

Adv Med Sci 2017 Sep 21;62(2):405-413. Epub 2017 Jun 21.

Indivumed GmbH, Falkenreid 88, Hamburg, Germany.

Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized. The continued identification of new genes and biomarkers specific to disease subtypes and individual patients is essential and inevitable for translation into personalized medicine, in estimating both, disease risk and response to therapy. Taking into consideration the mostly unsolved necessity of tailored therapy in oncology the innovative project MOBIT (molecular biomarkers for individualized therapy) was designed. The aims of the project are: (i) establishing integrative management of precise tumor diagnosis and therapy including systematic biobanking, novel imaging techniques, and advanced molecular analysis by collecting comprehensive tumor tissues, liquid biopsies (whole blood, serum, plasma), and urine specimens (supernatant; sediment) as well as (ii) developing personalized lung cancer diagnostics based on tumor heterogeneity and integrated genomics, transcriptomics, metabolomics, and radiomics PET/MRI analysis. It will consist of 5 work packages. In this paper the rationale of the Polish MOBIT project as well as its design is presented. (iii) The project is to draw interest in and to invite national and international, private and public, preclinical and clinical initiatives to establish individualized and precise procedures for integrating novel targeted therapies and advanced imaging techniques.
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http://dx.doi.org/10.1016/j.advms.2017.05.002DOI Listing
September 2017