International Journal of Molecular Sciences

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12 pages, 729 KiB

Open AccessArticle

Specific Receptors for the Chemokines CXCR2 and CXCR4 in Pancreatic Cancer

by Ala Litman-Zawadzka, Marta Łukaszewicz-Zając, Mariusz Gryko, Agnieszka Kulczyńska-Przybik, Bogusław Kędra and Barbara Mroczko

Int. J. Mol. Sci. 2020, 21(17), 6193; https://doi.org/10.3390/ijms21176193 - 27 Aug 2020

Cited by 4 | Viewed by 2001

Abstract

Background: The mortality rate of pancreatic cancer (PC) is equal to its incidence and the majority of PC patients die within a few months of diagnosis. Therefore, a search for new biomarkers useful in the diagnosis and prognosis of PC is ongoing. Objectives: [...] Read more.

Background: The mortality rate of pancreatic cancer (PC) is equal to its incidence and the majority of PC patients die within a few months of diagnosis. Therefore, a search for new biomarkers useful in the diagnosis and prognosis of PC is ongoing. Objectives: The aim of our study was to compare the utility of CXCR2 and CXCR4 in the diagnosis and prediction of PC with classical tumor marker (carcinoembryonic antigen, CEA) and marker of inflammation–C-reactive protein (CRP). Patients and Methods: The study comprised 64 subjects — 32 PC patients and 32 healthy volunteers. Serum concentrations of tested proteins were analysed using immunological methods. Results: Serum CXCR2 and CXCR4 concentrations, similarly to those of CEA and CRP, were significantly elevated in PC patients compared to healthy controls. Moreover, concentrations of CXCR4 were significantly correlated with CXCR2 and CRP levels, while CRP concentrations were correlated with CXCR2 and CEA levels. The diagnostic sensitivity and the predictive value for negative (PV_−ve) results for CXCR4 were similar to those of CEA and higher than those of CXCR2 and CRP, while the area under the ROC curve (AUC) for CXCR4 was the highest among all tested proteins (CXCR2, CEA, CRP). Moreover, serum CXCR2 was found to be a significant predictor of PC risk. Conclusions: CXCR4 is a better candidate for a tumor marker than CXCR2 in the diagnosis of PC, while serum CXCR2 is a significant predictor of PC risk. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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13 pages, 1798 KiB

Open AccessFeature PaperArticle

CXCL-8 in Preoperative Colorectal Cancer Patients: Significance for Diagnosis and Cancer Progression

by Sara Pączek, Marta Łukaszewicz-Zając, Mariusz Gryko, Piotr Mroczko, Agnieszka Kulczyńska-Przybik and Barbara Mroczko

Int. J. Mol. Sci. 2020, 21(6), 2040; https://doi.org/10.3390/ijms21062040 - 17 Mar 2020

Cited by 30 | Viewed by 3043

Abstract

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of [...] Read more.

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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Review

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13 pages, 434 KiB

Open AccessReview

The Role of Chemokines in the Development of Gastric Cancer—Diagnostic and Therapeutic Implications

by Elzbieta Pawluczuk, Marta Łukaszewicz-Zając and Barbara Mroczko

Int. J. Mol. Sci. 2020, 21(22), 8456; https://doi.org/10.3390/ijms21228456 - 10 Nov 2020

Cited by 16 | Viewed by 2226

Abstract

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific [...] Read more.

Gastric cancer (GC) is the fifth most common cancer worldwide and the second leading cause of cancer-related death. GC is usually diagnosed at an advanced stage due to late presentation of symptoms. Therefore, there is a need for establishing more sensitive and specific markers useful in early detection of the disease when a cancer is asymptomatic to improve the diagnostic and clinical decision-making process. Some researchers suggest that chemokines and their specific receptors play an important role in GC initiation and progression via promotion of angiogenesis, tumor transformation, invasion, survival and metastasis as well as protection from host response and inter-cell communication. Chemokines are small proteins produced by various cells such as endothelial cells, fibroblasts, leukocytes, and epithelial and tumor cells. According to our knowledge, the significance of chemokines and their specific receptors in diagnosing GC and evaluating its progression has not been fully elucidated. The present article offers a review of current knowledge on general characteristics of chemokines, specific receptors and their role in GC pathogenesis as well as their potential usefulness as novel biomarkers for GC. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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15 pages, 267 KiB

Open AccessReview

Neurodegeneration and Inflammation—An Interesting Interplay in Parkinson’s Disease

by Chrysoula Marogianni, Maria Sokratous, Efthimios Dardiotis, Georgios M. Hadjigeorgiou, Dimitrios Bogdanos and Georgia Xiromerisiou

Int. J. Mol. Sci. 2020, 21(22), 8421; https://doi.org/10.3390/ijms21228421 - 10 Nov 2020

Cited by 162 | Viewed by 10644

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation [...] Read more.

Parkinson’s disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut–brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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19 pages, 5987 KiB

Open AccessReview

Neurogranin and VILIP-1 as Molecular Indicators of Neurodegeneration in Alzheimer’s Disease: A Systematic Review and Meta-Analysis

by Maciej Dulewicz, Agnieszka Kulczyńska-Przybik and Barbara Mroczko

Int. J. Mol. Sci. 2020, 21(21), 8335; https://doi.org/10.3390/ijms21218335 - 6 Nov 2020

Cited by 16 | Viewed by 2907

Abstract

Neurogranin (Ng) and visinin-like protein 1 (VILIP-1) are promising candidates for Alzheimer’s Disease (AD) biomarkers closely related to synaptic and neuronal degeneration. Both proteins are involved in calcium-mediated pathways. The meta-analysis was performed in random effects based on the ratio of means (RoM) [...] Read more.

Neurogranin (Ng) and visinin-like protein 1 (VILIP-1) are promising candidates for Alzheimer’s Disease (AD) biomarkers closely related to synaptic and neuronal degeneration. Both proteins are involved in calcium-mediated pathways. The meta-analysis was performed in random effects based on the ratio of means (RoM) with calculated pooled effect size. The diagnostic utility of these proteins was examined in cerebrospinal fluid (CSF) of patients in different stages of AD compared to control (CTRL). Ng concentration was also checked in various groups with positive (+) and negative (-) amyloid beta (Aβ). Ng highest levels of RoM were observed in the AD (n = 1894) compared to CTRL (n = 2051) group (RoM: 1.62). Similarly, the VILIP-1 highest values of RoM were detected in the AD (n = 706) compared to CTRL (n = 862) group (RoM: 1.34). Concentrations of both proteins increased in more advanced stages of AD. However, Ng seems to be an earlier biomarker for the assessment of cognitive impairment. Ng appears to be related with amyloid beta, and the highest levels of Ng in CSF was observed in the group with pathological Aβ+ status. Our meta-analysis confirms that Ng and VILIP-1 can be useful CSF biomarkers in differential diagnosis and monitoring progression of cognitive decline. Although, an additional advantage of the protein concentration Ng is the possibility of using it to predict the risk of developing cognitive impairment in normal controls with pathological levels of Aβ1-42. Analyses in larger cohorts are needed, particularly concerning Aβ status. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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14 pages, 904 KiB

Open AccessReview

Alternatives to Insulin for the Regulation of Blood Sugar Levels in Type 2 Diabetes

by Stephen C. Bondy, Meixia Wu and Kedar N. Prasad

Int. J. Mol. Sci. 2020, 21(21), 8302; https://doi.org/10.3390/ijms21218302 - 5 Nov 2020

Cited by 4 | Viewed by 3242

Abstract

This short overview focuses on the causation and treatment of type 2 diabetes (T2D). Emphasis is given to the historical basis of understanding this disease and the background leading to emergence of the central role of insulin. The strengths of insulin administration in [...] Read more.

This short overview focuses on the causation and treatment of type 2 diabetes (T2D). Emphasis is given to the historical basis of understanding this disease and the background leading to emergence of the central role of insulin. The strengths of insulin administration in the treatment of diabetes are profound, but these need to be balanced against several serious shortcomings of its extended use. Some alternative approaches to T2D management are considered. Insulin is no longer considered as the first choice for type 2 diabetes, and an expanding range of new therapeutic possibilities is emerging. While these may lack the potency of insulin, at a minimum, they allow a major reduction in the intensity of insulin use. In view of the rising worldwide incidence of this disease, it is imperative to develop safe and inexpensive means of limiting its potential for impairment of normal functioning. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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19 pages, 678 KiB

Open AccessReview

MicroRNA Biomarkers in IBD—Differential Diagnosis and Prediction of Colitis-Associated Cancer

by Jaslin P. James, Lene Buhl Riis, Mikkel Malham, Estrid Høgdall, Ebbe Langholz and Boye S Nielsen

Int. J. Mol. Sci. 2020, 21(21), 7893; https://doi.org/10.3390/ijms21217893 - 24 Oct 2020

Cited by 64 | Viewed by 6385

Abstract

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). These are chronic autoimmune diseases of unknown etiology affecting the gastrointestinal tract. The IBD population includes a heterogeneous group of patients with varying disease courses requiring personalized treatment protocols. The complexity [...] Read more.

Inflammatory bowel disease (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). These are chronic autoimmune diseases of unknown etiology affecting the gastrointestinal tract. The IBD population includes a heterogeneous group of patients with varying disease courses requiring personalized treatment protocols. The complexity of the disease often delays the diagnosis and the initiation of appropriate treatments. In a subset of patients, IBD leads to colitis-associated cancer (CAC). MicroRNAs are single-stranded regulatory noncoding RNAs of 18 to 22 nucleotides with putative roles in the pathogenesis of IBD and colorectal cancer. They have been explored as biomarkers and therapeutic targets. Both tissue-derived and circulating microRNAs have emerged as promising biomarkers in the differential diagnosis and in the prognosis of disease severity of IBD as well as predictive biomarkers in drug resistance. In addition, knowledge of the cellular localization of differentially expressed microRNAs is a prerequisite for deciphering the biological role of these important epigenetic regulators and the cellular localization may even contribute to an alternative repertoire of biomarkers. In this review, we discuss findings based on RT-qPCR, microarray profiling, next generation sequencing and in situ hybridization of microRNA biomarkers identified in the circulation and in tissue biopsies. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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52 pages, 2022 KiB

Open AccessReview

The Role of Selected Chemokines and Their Receptors in the Development of Gliomas

by Magdalena Groblewska, Ala Litman-Zawadzka and Barbara Mroczko

Int. J. Mol. Sci. 2020, 21(10), 3704; https://doi.org/10.3390/ijms21103704 - 24 May 2020

Cited by 64 | Viewed by 6483

Abstract

Among heterogeneous primary tumors of the central nervous system (CNS), gliomas are the most frequent type, with glioblastoma multiforme (GBM) characterized with the worst prognosis. In their development, certain chemokine/receptor axes play important roles and promote proliferation, survival, metastasis, and neoangiogenesis. However, little [...] Read more.

Among heterogeneous primary tumors of the central nervous system (CNS), gliomas are the most frequent type, with glioblastoma multiforme (GBM) characterized with the worst prognosis. In their development, certain chemokine/receptor axes play important roles and promote proliferation, survival, metastasis, and neoangiogenesis. However, little is known about the significance of atypical receptors for chemokines (ACKRs) in these tumors. The objective of the study was to present the role of chemokines and their conventional and atypical receptors in CNS tumors. Therefore, we performed a thorough search for literature concerning our investigation via the PubMed database. We describe biological functions of chemokines/chemokine receptors from various groups and their significance in carcinogenesis, cancer-related inflammation, neo-angiogenesis, tumor growth, and metastasis. Furthermore, we discuss the role of chemokines in glioma development, with particular regard to their function in the transition from low-grade to high-grade tumors and angiogenic switch. We also depict various chemokine/receptor axes, such as CXCL8-CXCR1/2, CXCL12-CXCR4, CXCL16-CXCR6, CX3CL1-CX3CR1, CCL2-CCR2, and CCL5-CCR5 of special importance in gliomas, as well as atypical chemokine receptors ACKR1-4, CCRL2, and PITPMN3. Additionally, the diagnostic significance and usefulness of the measurement of some chemokines and their receptors in the blood and cerebrospinal fluid (CSF) of glioma patients is also presented. Full article

(This article belongs to the Special Issue Molecular Biomarkers of Selected Diseases of Civilization)

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