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.
The number of patients with Alzheimer’s Disease (AD) and other types of dementia disorders has drastically increased over the last decades. AD is a complex progressive neurodegenerative disease affecting about 14 million patients in Europe and the United States. The hallmarks of this disease are neurotic plaques consist of the Amyloid-β peptide (Aβ) and neurofibrillary tangles (NFTs) formed of hyperphosphorylated Tau protein (pTau). Currently, four CSF biomarkers: Amyloid beta 42 (Aβ42), Aβ42/40 ratio, Tau protein, and Tau phosphorylated at threonine 181 (pTau181) have been indicated as core neurochemical AD biomarkers. However, the identification of additional fluid biomarkers, useful in the prognosis, risk stratification, and monitoring of drug response is sorely needed to better understand the complex heterogeneity of AD pathology as well as to improve diagnosis of patients with the disease. Several novel biomarkers have been extensively investigated, and their utility must be proved and eventually integrated into guidelines for use in clinical practice. This paper presents the research and development of CSF and blood biomarkers for AD as well as their potential clinical significance. Graphic abstract Upper panel: Aβ peptides are released from transmembrane Amyloid Precursor Protein (APP) under physiological conditions (blue arrow). In AD, however, pathologic accumulation of Aβ monomers leads to their accumulation in plaques (red arrow). This is reflected in decreased concentration of Aβ1-42 and decreased Aβ42/40 concentration ratio in the CSF. Lower panel: Phosphorylated Tau molecules maintain axonal structures; hyperphosphorylation of Tau (red arrow) in AD leads to degeneration of axons, and release of pTau molecules, which then accumulate in neurofibrillary tangles. This process is reflected by increased concentrations of Tau and pTau in the CSF.
Every year, almost 2 million people develop colorectal cancer (CRC), which makes it the fourth most common malignancy worldwide. It is also estimated that approximately 48% of CRC patients will die from the disease. Thus, noninvasive and accurate methods for early detection and prevention of CRC are sorely needed. It is suggested that C-X-C motif ligand 1 (CXCL1) and C-X-C motif ligand 8 (CXCL8) as well as their cognate receptors can mediate tumor growth, proliferation, survival, neoangiogenesis and metastasis of malignant cells, including CRC. However, little is known about the clinical significance of these proteins as potential biomarkers for CRC. Therefore, in our review, we performed a comprehensive literature search using the PubMed database to identify original articles that investigated whether CXCL1 and CXCL8 and their receptors play a role in CRC pathogenesis. In summary, our review highlighted the potential significance of CXCL1/CXCR2 and CXCL8/CXCR1,-2 in the diagnosis and progression of CRC as well as indicated their potential therapeutic significance. However, given the non-specific nature of analyzed chemokines and a small number of studies concerning the assessment of blood concentration of these proteins in CRC patients, investigations need to be continued in the future before selected chemokines could be established as biomarkers for CRC.
Background: A growing body of evidence highlights the crucial role of neuroinflammation and chemokine involvement in cognitive impairment pathophysiology. Fractalkine (CX3CL1) appears to be a relevant causative factor in the development of dementia, particularly at the early stages of the disease. However, limited data are available on the levels of CX3CL1 in the cerebrospinal fluid (CSF) and blood. Additionally, to date, its utility as a biomarker for MCI or AD has not been studied. Objective: The aim of the present study was to evaluate the clinical utility of CX3CL1 in the early diagnosis of cognitive impairment. We also compared the diagnostic usefulness of CX3CL1 with other biomarkers associated with neuroinflammation. Method: A total of 60 patients with cognitive impairment, including 42 patients with AD and 18 subjects with MCI, as well as 20 cognitively healthy controls were enrolled in the study. CSF and blood concentrations of CX3CL1, CCL-2, and YKL40 were measured by ELISA. Results: Significantly higher CSF and blood concentrations of CX3CL1 were observed in MCI and AD patients compared to older individuals without cognitive impairment. The increase in the levels of CX3CL1 and YKL-40 in non-demented subjects was associated with MCI. The area under the ROC curve for CX3CL1 in MCI subjects was larger in comparison to classical AD markers. Conclusion: Presented results indicate a crucial role of CX3CL1 in the pathology of cognitive impairment and the potential usefulness of this protein in the early diagnosis of MCI and AD.
Alzheimer’s disease (AD) is a progressive condition and the most common cause of dementia worldwide. The neuropathological changes characteristic of the disorder can be successfully detected before the development of full-blown AD. Early diagnosis of the disease constitutes a formidable challenge for clinicians. CSF biomarkers are the in vivo evidence of neuropathological changes developing in the brain of dementia patients. Therefore, measurement of their concentrations allows for improved accuracy of clinical diagnosis. Moreover, AD biomarkers may provide an indication of disease stage. Importantly, the CSF biomarkers of AD play a pivotal role in the new diagnostic criteria for the disease, and in the recent biological definition of AD by the National Institute on Aging, NIH and Alzheimer’s Association. Due to the necessity of collecting CSF by lumbar puncture, the procedure seems to be an important issue not only from a medical, but also a legal, viewpoint. Furthermore, recent technological advances may contribute to the automation of AD biomarkers measurement and may result in the establishment of unified cut-off values and reference limits. Moreover, a group of international experts in the field of AD biomarkers have developed a consensus and guidelines on the interpretation of CSF biomarkers in the context of AD diagnosis. Thus, technological advancement and expert recommendations may contribute to a more widespread use of these diagnostic tests in clinical practice to support a diagnosis of mild cognitive impairment (MCI) or dementia due to AD. This review article presents up-to-date data regarding the usefulness of CSF biomarkers in routine clinical practice and in biomarkers research.
Reticulons (RTNs) are crucial regulatory factors in the central nervous system (CNS) as well as immune system and play pleiotropic functions. In CNS, RTNs are transmembrane proteins mediating neuroanatomical plasticity and functional recovery after central nervous system injury or diseases. Moreover, RTNs, particularly RTN4 and RTN3, are involved in neurodegeneration and neuroinflammation processes. The crucial role of RTNs in the development of several neurodegenerative diseases, including Alzheimer’s disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), or other neurological conditions such as brain injury or spinal cord injury, has attracted scientific interest. Reticulons, particularly RTN-4A (Nogo-A), could provide both an understanding of early pathogenesis of neurodegenerative disorders and be potential therapeutic targets which may offer effective treatment or inhibit disease progression. This review focuses on the molecular mechanisms and functions of RTNs and their potential usefulness in clinical practice as a diagnostic tool or therapeutic strategy.
According to the projections of the statistical office of the European Union, Eurostat, nearly one third of EU citizens will be at least 65 in 2060. The U.S. population age 65 and older continues to increase and is projected to nearly double from 48 million to 88 million by 2050. Elderly people are especially exposed to neurodegenerative diseases (NDs). The most common ND is Alzheimer's disease (AD), a chronic and progressive disorder with a variety of pathological changes within neuronal tissue, which begin even 10-15 years before the onset of cognitive impairment symptoms. AD is perceived as a disease continuum and considered to include three basic phases: preclinical (asymptomatic) stage, mild cognitive impairment (MCI), and dementia due to AD. A very important issue, from medical and legal perspectives, is the NDs patient's consent to medical procedures, including diagnostic procedures, such as lumber puncture. NDs patients are not always able to express their consent and do not always understand the information provided by a physician. This applies to a group of patients in the final stages of NDs. This paper presents legal regulations of selected European countries and signalizes the U.S. legal solutions on the issue of NDs patients' informed consent to medical procedures.
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