scholarly journals The Diagnostic Usefulness of Circulating Profile of Extracellular Matrix Components: Sulfated Glycosaminoglycans (sGAG), Hyaluronan (HA) and Extracellular Part of Syndecan-1 (sCD138) in Patients with Crohn’s Disease and Ulcerative Colitis

2021 ◽  
Vol 10 (8) ◽  
pp. 1722
Author(s):  
Alicja Derkacz ◽  
Paweł Olczyk ◽  
Agnieszka Jura-Półtorak ◽  
Krystyna Olczyk ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Ulcerative Colitis ◽  
Extracellular Matrix ◽  
Ecm Remodeling ◽  
Mayo Score ◽  
Extracellular Matrix Components ◽  
Adalimumab Therapy ◽  
Bowel Diseases ◽  
Diagnostic Usefulness ◽  
Quantitative Changes ◽  
One Year

The described research focused on the diagnostic usefulness of sulfated glycosaminoglycans (sGAG), hyaluronan (HA), and extracellular part of syndecan-1 (sCD138) as new markers related to extracellular matrix (ECM) remodeling in the intestine during the two most common forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn’ disease (CD). Inflammatory markers belonging to ECM components were assessed in serum of patients with IBD using an immunoenzymatic method (HA and sCD138) and a method based on the reaction with dimethylmethylene blue (sulfated GAG). Measurements were carried out twice: at baseline and after one year of therapy with prednisone (patients with CD) or adalimumab (patients with UC). No quantitative changes were observed in serum sGAG, HA, and sCD138 concentrations between patients newly diagnosed with CD and the healthy group. In the case of patients with UC, the parameter which significantly differentiated healthy subjects and patients with IBD before biological therapy was HA. Significant correlation between serum HA level and inflammation activity, expressed as Mayo score, was also observed in patients with UC. Moreover, the obtained results have confirmed that steroid therapy with prednisone significantly influenced the circulating profile of all examined ECM components (sGAG, HA, and sCD138), whereas adalimumab therapy in patients with UC led to a significant change in only circulating sGAG levels. Moreover, the significant differences in serum HA levels between patients with UC and CD indicate that quantification of circulating HA may be useful in the differential diagnosis of CD and UC.

scholarly journals The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases

2021 ◽  
Vol 10 (5) ◽  
pp. 1122
Author(s):  
Alicja Derkacz ◽  
Paweł Olczyk ◽  
Krystyna Olczyk ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Extracellular Matrix ◽  
Inflammatory Bowel Diseases ◽  
Healing Process ◽  
Immunological Response ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Intestinal Fibrosis ◽  
Extracellular Matrix Components ◽  
Bowel Diseases ◽  
Inflammatory Bowel

The remodeling of extracellular matrix (ECM) within the intestine tissues, which simultaneously involves an increased degradation of ECM components and excessive intestinal fibrosis, is a defining trait of the progression of inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD). The increased activity of proteases, especially matrix metalloproteinases (MMPs), leads to excessive degradation of the extracellular matrix and the release of protein and glycoprotein fragments, previously joined with the extracellular matrix, into the circulation. MMPs participate in regulating the functions of the epithelial barrier, the immunological response, and the process of wound healing or intestinal fibrosis. At a later stage of fibrosis during IBD, excessive formation and deposition of the matrix is observed. To assess changes in the extracellular matrix, quantitative measurement of the concentration in the blood of markers dependent on the activity of proteases, involved in the breakdown of extracellular matrix proteins as well as markers indicating the formation of a new ECM, has recently been proposed. This paper describes attempts to use the quantification of ECM components as markers to predict intestinal fibrosis and evaluate the healing process of the gut. The markers which reflect increased ECM degradation, together with the ones which show the process of creating a new matrix during IBD, allow the attainment of important information regarding the changes in the intestinal tissue, epithelial integrity and extracellular matrix remodeling. This paper contains evidence confirming that ECM remodeling is an integral part of directional cell signaling in the progression of IBD, and not only a basis for the ongoing processes.

scholarly journals Evaluation of efficacy and comparative frequency of adverse events in patients with ulcerative colitis receiving the original infliximab and its biosimilar. One year of observation

2019 ◽  
Vol 91 (8) ◽  
pp. 41-46
Author(s):  
O V Knyazev ◽  
T V Shkurko ◽  
A V Kagramanova ◽  
A A Lishchinskaya ◽  
M Yu Zvyaglova ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Real Life ◽  
Fecal Calprotectin ◽  
Biologic Drugs ◽  
Real Life Data ◽  
Bowel Diseases ◽  
Significant Clinical Improvement ◽  
One Year

Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking. Aim. To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. Materials and methods. Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. Results and discussion. Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. Conclusion. IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.

scholarly journals Asymptomatic and Persistent Elevation of Pancreatic Enzymes in an Ulcerative Colitis Patient

2013 ◽  
Vol 2013 ◽  
pp. 1-4 ◽  
Author(s):  
Elisa Liverani ◽  
Filippo Leonardi ◽  
Lucia Castellani ◽  
Carla Cardamone ◽  
Andrea Belluzzi
Keyword(s):  
Ulcerative Colitis ◽  
Acute Pancreatitis ◽  
Serum Amylase ◽  
Drug Dosage ◽  
Pancreatic Disease ◽  
Pancreatic Enzymes ◽  
Pancreatic Damage ◽  
Bowel Diseases ◽  
One Year ◽  
Asymptomatic Elevation

Azathioprine has been extensively used in the management of inflammatory bowel diseases. It might cause pancreatic damage in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis. Here we report the case of a 61-year-old patient with ulcerative colitis who had been treated with azathioprine for three years, achieving clinical remission. During treatment he presented an asymptomatic elevation of serum pancreatic enzymes, without any signs of pancreatitis at imaging. This evidence brought us to reassess the drug dosage, without achieving a normalization of biochemical analysis. Autoimmune pancreatitis was excluded. One year after the suspension of azathioprine, we still face persistent high levels of amylase/lipase. Normalization of enzymatic values in patients who develop intolerance to azathioprine, in the form of either asymptomatic elevation in serum amylase/lipase or overt acute pancreatitis, is usually achieved in about two months after stopping drug intake. Asymptomatic elevation in serum pancreatic enzymes in the absence of pancreatic disease is reported in the literature and defined as “Gullo’s syndrome,” but nobody of the subjects studied had been treated in the past with pancreatotoxic drugs. Might this case be defined as “benign pancreatic hyperenzymemia”?

scholarly journals The efficacy and safety of tacrolimus suppositories in patients with localized ulcerative colitis

2020 ◽  
Author(s):  
Shizuma Omote ◽  
Tatsuya Toyokawa ◽  
Ryohei Sumii ◽  
Akira Nakanishi ◽  
Yuka Kadowaki ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Adverse Events ◽  
Blood Concentration ◽  
Efficacy And Safety ◽  
Monitoring Methods ◽  
Once Daily ◽  
Mayo Score ◽  
Amino Salicylic Acid ◽  
One Year ◽  
Dose Change

Abstract Background Tacrolimus is a calcineurin inhibitor used for the treatment of 5-Amino-salicylic acid (5-ASA) and systematic corticosteroid refractory ulcerative colitis. However, systemic administration of tacrolimus could lead to many adverse events. Therefore, we used tacrolimus suppositories as a local therapeutic agent and examined its efficacy and safety with strict blood concentration monitoring. Methods Sixteen patients with ulcerative colitis were administered a 0.5-mg tacrolimus suppository once daily. In cases with an insufficient clinical effect, additional amounts, at an increment of 0.5 mg of tacrolimus, were administered. The blood concentration was measured two weeks after the start of treatment or any dose change and every four weeks thereafter. Results The partial Mayo score was 5.31 before the start of treatment, and it decreased significantly after 2 (2.56, P = 0.001), 4 (1.53, P < 0.001), and 8 (1.47, P = < 0.001) weeks of treatment. The median duration of tacrolimus treatment was 24 (range 2–96) weeks, and 6 patients were treated continuously for more than one year after the pMayo score improved. No exacerbation of adverse events during the treatment regimen was observed. The effects and safety of tacrolimus suppositories were verified with strict blood concentration monitoring. Conclusions Our findings suggest that the application of tacrolimus suppositories is safe and effective in the treatment of patients with ulcerative colitis.

scholarly journals Cancer Cell-derived Secretory Factors in Breast Cancer-associated Lung Metastasis: Their Mechanism and Future Prospects

2020 ◽  
Vol 20 (3) ◽  
pp. 168-186 ◽  
Author(s):  
Tabinda Urooj ◽  
Bushra Wasim ◽  
Shamim Mushtaq ◽  
Syed Nudrat Nawaid Shah ◽  
Muzna Shah
Keyword(s):  
Breast Cancer ◽  
Extracellular Matrix ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Primary Site ◽  
Ecm Remodeling ◽  
Metastatic Cells ◽  
Extracellular Matrix Components ◽  
Matrix Components

: In Breast cancer, Lung is the second most common site of metastasis after the bone. Various factors are responsible for Lung metastasis occurring secondary to Breast cancer. Cancer cellderived secretory factors are commonly known as ‘Cancer Secretomes’. They exhibit a prompt role in the mechanism of Breast cancer lung metastasis. They are also major constituents of hostassociated tumor microenvironment. Through cross-talk between cancer cells and the extracellular matrix components, cancer cell-derived extracellular matrix components (CCECs) such as hyaluronan, collagens, laminin and fibronectin cause ECM remodeling at the primary site (breast) of cancer. However, at the secondary site (lung), tenascin C, periostin and lysyl oxidase, along with pro-metastatic molecules Coco and GALNT14, contribute to the formation of pre-metastatic niche (PMN) by promoting ECM remodeling and lung metastatic cells colonization. Cancer cell-derived secretory factors by inducing cancer cell proliferation at the primary site, their invasion through the tissues and vessels and early colonization of metastatic cells in the PMN, potentiate the mechanism of Lung metastasis in Breast cancer. : On the basis of biochemical structure, these secretory factors are broadly classified into proteins and non-proteins. This is the first review that has highlighted the role of cancer cell-derived secretory factors in Breast cancer Lung metastasis (BCLM). It also enumerates various researches that have been conducted to date in breast cancer cell lines and animal models that depict the prompt role of various types of cancer cell-derived secretory factors involved in the process of Breast cancer lung metastasis. In the future, by therapeutically targeting these cancer driven molecules, this specific type of organ-tropic metastasis in breast cancer can be successfully treated.

scholarly journals Healthy Subcutaneous and Omental Adipose Tissue Is Associated with High Expression of Extracellular Matrix Components

2022 ◽  
Vol 23 (1) ◽  
pp. 520
Author(s):  
Matúš Soták ◽  
Meenu Rohini Rajan ◽  
Madison Clark ◽  
Christina Biörserud ◽  
Ville Wallenius ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Adipose Tissue ◽  
Lysyl Oxidase ◽  
Subcutaneous Fat ◽  
High Expression ◽  
Adipose Tissues ◽  
Ecm Remodeling ◽  
Omental Adipose Tissue ◽  
Extracellular Matrix Components ◽  
Metabolic Conditions

Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins, e.g., lysyl oxidase and thrombospondin. Our data suggests that subcutaneous fat is more prone to express proteins involved in ECM remodeling than omental adipose tissues. We conclude that a more dynamic ability to deposit and remodel ECM may be a key signature of healthy adipose tissue, and that subcutaneous fat may adapt more readily to changing metabolic conditions than omental fat.

scholarly journals Linking Oxidative Stress and DNA Damage to Changes in the Expression of Extracellular Matrix Components

2021 ◽  
Vol 12 ◽  
Author(s):  
Susana G. Martins ◽  
Rita Zilhão ◽  
Sólveig Thorsteinsdóttir ◽  
Ana Rita Carlos
Keyword(s):  
Oxidative Stress ◽  
Extracellular Matrix ◽  
Dna Damage ◽  
Uv Light ◽  
Tissue Homeostasis ◽  
Strong Impact ◽  
Ecm Remodeling ◽  
Extracellular Matrix Components ◽  
Genes Encoding ◽  
Negative Impacts

Cells are subjected to endogenous [e.g., reactive oxygen species (ROS), replication stress] and exogenous insults (e.g., UV light, ionizing radiation, and certain chemicals), which can affect the synthesis and/or stability of different macromolecules required for cell and tissue function. Oxidative stress, caused by excess ROS, and DNA damage, triggered in response to different sources, are countered and resolved by specific mechanisms, allowing the normal physiological equilibrium of cells and tissues to be restored. One process that is affected by oxidative stress and DNA damage is extracellular matrix (ECM) remodeling, which is a continuous and highly controlled mechanism that allows tissues to readjust in reaction to different challenges. The crosstalk between oxidative stress/DNA damage and ECM remodeling is not unidirectional. Quite on the contrary, mutations in ECM genes have a strong impact on tissue homeostasis and are characterized by increased oxidative stress and potentially also accumulation of DNA damage. In this review, we will discuss how oxidative stress and DNA damage affect the expression and deposition of ECM molecules and conversely how mutations in genes encoding ECM components trigger accumulation of oxidative stress and DNA damage. Both situations hamper the reestablishment of cell and tissue homeostasis, with negative impacts on tissue and organ function, which can be a driver for severe pathological conditions.

scholarly journals P489 Rescue treatment with original versus biosimilar infliximab in biologic-naïve patients with moderate-severe Ulcerative Colitis and corticosteroid failure

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S475-S475
Author(s):  
C Muñoz-Villafranca ◽  
M Á Ogueta ◽  
P Ramírez de la Piscina ◽  
B Álvarez-Herrero ◽  
A Loizate ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Colonic Mucosa ◽  
Rescue Therapy ◽  
Basque Country ◽  
Clinical Activity ◽  
Severe Ulcerative Colitis ◽  
Mayo Score ◽  
Rescue Treatment ◽  
Significant Difference ◽  
One Year

Abstract Background Infliximab is effective as rescue therapy in moderate-severe Ulcerative Colitis (UC). Subsequently, a biosimilar of infliximab has been approved for the same indications, as its effectiveness is considered similar to the original infliximab. Our aim was to analyse the colectomy rate and the efficacy of original infliximab (Remicade®) versus biosimilar infliximab (Inflectra®) in patients with moderate-severe UC who failed to respond to intravenous corticosteroids. Methods We performed a retrospective and observational study in two hospitals in the Basque Country. All patients hospitalised between 2010–2020 with moderate-severe UC, without response to intravenous corticosteroids and rescue treatment with infliximab were consecutively included. Two cohorts were established: the first one from 2010 to 2015 in patients treated with Remicade®, and the second one from 2015 to 2020 in patients with Inflectra®. We assessed all patients that had received at least one dose of infliximab. Patients were followed for a period of one year until loss of response or colectomy. Early colectomy is the surgery performed until week 12, and late colectomy between week 12 and one year. At the moment of hospitalisation all patients were clinically and endoscopically evaluated by Mayo Score. The clinical response was assessed in week 14 and 52. Results A total of 85 patients were evaluated, 53 (64.4%) in Remicade® group and 32 (37.6%) in Inflectra® group. 21.17% (18/85) of the patients had a colectomy in one year. 77.7% of the colectomies took place in the first 12 weeks (14/18, 7 patient in each group). Rates of early (13.8% vs 21.9%, p=0.297) and late colectomy (17% vs 28.1%, p=0.223) showed a numerical but non-statistically significant difference in favour of Remicade®. Transfusion (OR=4.20, IC 95% [1.38–12.77], p=0.011) and the presence of cytomegalovirus in the colonic mucosa (OR=4.07, IC 95% [1.31–12.63], p=0.015) were univariate predictors of colectomy. A statistically significant difference was found in clinical remission at week 14 (49.1% vs 25%, p=0.040) but not at week 52 (73.7% vs 50%, p=0.074) in patients with Remicade® versus Inflectra®. Neither clinical activity nor mucosa activity showed relationship with risk of colectomy. Conclusion 1. The rescue therapy with infliximab in patients with moderate-severe Ulcerative Colitis who failed to respond to intravenous corticosteroids could show a favourable trend for Remicade® against Inflectra®. However, further research is needed to confirm it. 2. The need of transfusion and the presence of cytomegalovirus in the colonic mucosa could be predictive factors of colectomy.

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