TDP-43 pathology in subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis (SSPE) is a fatal, slowly progressive brain disorder caused by a mutated measles virus. Both subacute inflammatory and neurodegenerative mechanisms appear to play significant roles in the pathogenesis. TAR DNA-binding protein 43 (TDP-43) inclusions are a common co-pathology in several neurodegenerative disorders with diverse pathogenesis. In the present study, we examined brains of 16 autopsied SSPE patients for the presence of TDP-43 pathology and possible associations with tau pathology. Immunohistochemical staining identified TDP-43 inclusions in 31% of SSPE cases. TDP-43 pathology was widely distributed in the brains, most severely in the atrophied cerebral cortex (temporal and parietal), and most frequently as tangle- and thread-like neuronal cytoplasmic inclusions. It was associated with longer disease duration (>4 years) and tau pathology (all TDP-43-positive cases had tau-positive neurofibrillary tangles). This study demonstrates for the first time an association between TDP-43 pathology and SSPE. The co-occurrence of TDP-43 and tau aggregates and correlation with the disease duration suggest that both pathological proteins are involved in the neurodegenerative process induced by viral inflammation.

Incidence and morphology of secondary TDP-43 proteinopathies: Part 2.

Transactivation (TAR) DNA binding protein 43 kDa (TDP-43) inclusions frequently occur as a comorbid pathology in several neurodegenerative disorders, including Alzheimer's disease, Huntington's disease, Lewy body disease, and progressive supranuclear palsy, and may appear in association with nondegenerative neurological etiology, for example neoplastic, paraneoplastic, traumatic, or infectious. Relationships between various pathological proteins and mechanisms associated with TDP-43-induced neurodegeneration are still not fully understood. Thus, overlap of distinct neuropathological mechanisms frequently leads to greater brain atrophy and a more severe clinical course, suggesting the importance of co-pathologies in ante-mortem diagnosing and treatment. The present review aims to discuss the incidence, morphology, and role of TDP-43 pathology in the context of other dominant, hallmark pathologies, referred to as secondary TDP-43 proteinopathies. The previous part (Part 1) focused on common neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, and Lewy body disease, while the present part (Part 2) discusses TDP-43 pathology in rare neurodegenerative diseases and neurological diseases with nondegenerative etiology.

Influence of SARS-CoV-2 on Adult Human Neurogenesis.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with the onset of neurological and psychiatric symptoms during and after the acute phase of illness. Inflammation and hypoxia induced by SARS-CoV-2 affect brain regions essential for fine motor function, learning, memory, and emotional responses. The mechanisms of these central nervous system symptoms remain largely unknown. While looking for the causes of neurological deficits, we conducted a study on how SARS-CoV-2 affects neurogenesis. In this study, we compared a control group with a group of patients diagnosed with COVID-19. Analysis of the expression of neurogenesis markers showed a decrease in the density of neuronal progenitor cells and newborn neurons in the SARS-CoV-2 group. Analysis of COVID-19 patients revealed increased microglial activation compared with the control group. The unfavorable effect of the inflammatory process in the brain associated with COVID-19 disease increases the concentration of cytokines that negatively affect adult human neurogenesis.

Influence of Basalt Aggregate Crushing Technology on Its Geometrical Properties-Preliminary Studies.

The use of mineral aggregates is related to the increasing demand in construction, railway and road infrastructures. However, mineral aggregates can appear to be of variable quality, directly affecting their suitability for respective earthwork applications. Since the production of mineral aggregates should ensure the standardized, high-quality requirements of the final product, rock-crushing mechanisms should be investigated in a detailed manner. In this context, the aim of the present study is to evaluate and analyze the geometric parameters of basalt aggregates as a result of several rock comminution processes. Basalt aggregates from two deposits in Poland were used in the study. The samples are differentiated regarding both lithological variances, mineral composition as well as the host rock's tuff content. The rock comminution processes were conducted using two types of crushers, namely the laboratory-scale jaw and cone crushers. The feed for crushing was designed based on the original geometric grain composition and the separated feed in the form of flaky and non-flaky particles. The crushability test results demonstrated that the interparticle compression in the jaw crusher resulted in finer products compared to the one in the cone crusher. It was also observed that the flakiness and shape indexes decreased after crushing, both in the feed with the original geometric composition of the grains and those with flaky and non-flaky particles. Nevertheless, a higher flakiness index was obtained after the crushing of non-flaky particles and a lower one after the crushing of flaky particles. The flakiness index for grains below 16 mm after the crushing process was less than 10%, which indicates a more favorable result compared to the original feed. In addition, it was shown that flaky and non-cubical particles were accumulated in the finest (below 8 mm) and coarsest (above 20 mm) fractions in jaw and cone crushing processes, receiving flakiness and shape indexes ranging up to 80-100%. Finally, it was also observed that the lithological variances of the feed material have a significant impact on the particle size distribution of the product. More profoundly, basalt aggregates with a higher tuff content and weathering degree have a higher degree of crushing. The present study, in this context, provides accurate and satisfying information on understanding the crushing mechanisms of two important crushing equipment as well as their rock-crusher interactions.

Incidence and morphology of secondary TDP-43 proteinopathies: Part 1.

Transactive response DNA binding protein of 43 kDa (TDP-43) is considered to play an essential role in the pathogenesis of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Growing body of evidence indicate that pathological TDP-43 inclusions frequently occur in the context of other distinctive hallmark pathologies, referred to as secondary TDP-43 proteinopathies. Comorbid TDP-43 pathology is well-documented in several neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, or progressive supranuclear palsy. It may also appear as a consequence of less obvious disease etiologies, i.e. post-traumatic (chronic traumatic encephalopathy), neoplastic (pilocytic astrocytoma), or post-infectious (post-encephalitic parkinsonism). The aim of the present review was to evaluate the incidence, morphology, and role of TDP-43 pathology in the secondary TDP-43 proteinopathies. This article (Part 1) discussed TDP-43 pathology in more common neurodegenerative diseases, including Alzheimer's disease, Lewy body disease, Huntington's disease, multiple system atrophy, corticobasal degeneration, and progressive supranuclear palsy. A follow-up article (Part 2) will describe abnormal TDP-43 changes in rare neurodegenerative diseases or neurological diseases with nondegenerative etiology.

Activation of the 5-HT7 receptor and MMP-9 signaling module in the hippocampal CA1 region is necessary for the development of depressive-like behavior.

Major depressive disorder is a complex disease resulting from aberrant synaptic plasticity that may be caused by abnormal serotonergic signaling. Using a combination of behavioral, biochemical, and imaging methods, we analyze 5-HT7R/MMP-9 signaling and dendritic spine plasticity in the hippocampus in mice treated with the selective 5-HT7R agonist (LP-211) and in a model of chronic unpredictable stress (CUS)-induced depressive-like behavior. We show that acute 5-HT7R activation induces depressive-like behavior in mice in an MMP-9-dependent manner and that post mortem brain samples from human individuals with depression reveal increased MMP-9 enzymatic activity in the hippocampus. Both pharmacological activation of 5-HT7R and modulation of its downstream effectors as a result of CUS lead to dendritic spine elongation and decreased spine density in this region. Overall, the 5-HT7R/MMP-9 pathway is specifically activated in the CA1 subregion of the hippocampus during chronic stress and is crucial for inducing depressive-like behavior.

Impact of inflammation-related degenerative changes on the wall strength of unruptured intracranial aneurysms: a pilot study.

INTRODUCTION: Saccular intracranial aneurysm (sIA) rupture is a serious cerebrovascular event associated with inflammatory destructive processes leading to gradual weakening of the sIA wall. The aim of the present study was to identify the morphological and histological determinants for low wall strength in unruptured sIAs harvested from autopsy subjects. MATERIAL AND METHODS: A total of eight single unruptured sIAs were identified and excised with adjacent cerebral arteries during 8 of 184 postmortem examinations. The dome morphology was assessed for each sIA at a constant pressure of 100 mmHg. Then, after 5 preconditioning cycles which assured muscle fibre relaxation, sIA specimens were subjected to gradually increasing intraluminal pressure at a rate of 20 mmHg/s until rupture of the sIA or cerebral artery was achieved. Micro-structural degenerative changes and inflammatory cell infiltration within the sIA wall were quantitatively analysed after pressurization of the sIA specimens. The microscopic analysis of the slides stained with histological methods (HE, Mallory trichrome, Masson trichrome, orcein) and immunohistochemical methods (LCA, CD3, CD68) was performed. RESULTS: The wall of the sIA ruptured in three specimens, while in the other cases, rupture occurred at the arterial wall. The mean maximal dome size was significantly larger in sIAs with low wall strength, that is, in sIAs that ruptured during pressurization, than in sIAs with high wall strength (6.46 mm vs. 2.43 mm, p = 0.034). Moreover, a significantly higher average percentage of wall hyalinization in sIAs that ruptured than in sIAs that did not rupture was observed (30% vs. 0%, p = 0.006). In contrast, the degree of inflammatory cell infiltration did not differ between the wall strength categories. CONCLUSIONS: Our results support the observations that larger sIAs may be at a higher risk of rupture. Histological analysis revealed that hyalinization corresponds to the weakened regions of the wall of unruptured sIAs.

Evaluation of the Structure and Geometric Properties of Crushed Igneous Rock Aggregates.

The aim of this publication is to analyze the influence of rock mineral composition and rock geometric properties on the quality of crushed aggregates, from the perspective of selecting an adequate aggregate production technology. This research is based on samples of crushed aggregates from plants processing igneous rocks from four different igneous deposits. In the case of the geometric properties, shape and flakiness indexes were identified and subsequently analyzed along with particle size distribution. The performed tests allowed a conclusion that the shape of the particle is influenced by the mineral composition and size distribution. The grain size analysis demonstrated that flaky and non-cubical particles concentrate in the finest grain fractions, and the least variable shape index is observed for basalt aggregate. Some problems were also observed to exist in relation to the classification of grain shape. In the literature, the notions of regular and irregular grains seem to be used interchangeably with the notions of flaky and non-flaky grains. The performed tests show that flaky grains do not necessarily have to be non-cubical and vice versa. Therefore, this article proposes an approach in which the applied technique is precisely explained and the shape of grains is described with four notions: cubical, non-cubical, flaky, and non-flaky. The article also finally concludes that the next step in the research on selecting an optimal production technology of high-quality aggregates should be to analyze the selection of the fragmentation process while also characterizing the geometric properties of the aggregates.

Neuropathological Changes in the Brains of Suicide Killers.

BACKGROUND: Homicide combined with subsequent suicide of the perpetrator is a particular form of interpersonal violence and, at the same time, a manifestation of extreme aggression directed against oneself. Despite the relatively well-described individual acts of homicide and suicide, both in terms of psychopathology and law, acts of homicide and subsequent suicide committed by the same person are not well-studied phenomena. The importance of emotional factors, including the influence of mental state deviations (psychopathology), on this phenomenon, is discussed in the literature, but still there is relatively little data with which to attempt neuropathological assessments of the brains of suicide killers. This paper is dedicated to the issue based on the neuropathological studies performed. METHODS: We analyzed a group of murder-suicides using histochemical and immunohistochemical methods. RESULTS: The results of our research indicate the presence of neurodegenerative changes including multiple deposits of ß-amyloid in the form of senile/amyloid plaques and perivascular diffuse plaques. CONCLUSIONS: Neurodegenerative changes found in the analyzed brains of suicide killers may provide an interesting starting point for a number of analyses. The presence of neurodegenerative changes at such a young age in some murderers may suggest preclinical lesions that affect cognitive functions and are associated with depressed moods.

Neuropathological analysis of the brains of fifty-two patients with COVID-19.

Coronavirus disease 2019 (COVID-19) poses a global challenge to healthcare and society in the early 21st century. We report neuropathological changes in 52 patients aged between 22 years and 88 years (median 58 years) who were infected with the CoV-2 coronavirus. Patients died under various circumstances and had various pre-existing diseases. The inclusion criteria for this study were: positive result for the nasopharyngeal swab for SARS-CoV-2 RNA, diagnosis of pneumonia of SARS-CoV-2 or nucleoproteins of SARS-CoV-2 in pulmonary tissue confirmed by immunohistochemical methods (IHC). Samples from all brain structures and lung specimens were taken for histopathological examinations. Brain and pulmonary samples were stained typically with histological and immunohistochemical methods and small tissue fragments were examined with the transmission electron microscope (TEM). The light and electron microscopy examination confirmed the numerous neuropathological changes in the brains of the patients infected with the CoV-2. Many of these changes were caused by pre-existing diseases of patients and/or by necessary treatment. However, vascular lesions and the inflammatory process seem to be characteristic of the CoV-2 infection. In all of the structures of 52 brains of patients, damage of the vessel walls and morphological feature of the damage to the blood-brain barrier were observed. Lymphocytic and microglial infiltrates, both perivascular and diffuse, were also observed. Hence, the brain changes due to COVID-19 infection, could be called COVID-19 cerebral angiopathy with diffuse inflammation.

Ultrastructure of mitochondria and damage to small blood vessels in siblings with the same mutation in the NOTCH 3 and coexisting diseases.

We performed ultrastructural studies of mitochondria and evaluated the appearance of small blood vessels of three middle-aged siblings affected by the same mutation in the NOTCH3 gene, causing CADASIL. CADASIL pathognomonic features include granular osmiophilic material (GOM), which we observed. GOMs were located in damaged and thickened basement membranes (BM) of capillaries and arterioles. Our patients were also burdened by type II diabetes (first patient), impaired glucose metabolism (second patient), and hypertension (third patient). The ultrastructure of the capillaries in the first and second patients differed from the third patient. In diabetes/impaired glucose metabolism patients (first and second patients), we observed: pathologies of mitochondria in damaged endothelium and pericytes of capillaries; extremely thickened (BM) with visible remains of vascular cells; well-preserved GOMs anchored in the rebuilt capillary extracellular matrix. We identified degenerated or vestigial small blood vessels of skeletal muscles in the first patient. The capillary damage in the third patient (with hypertension) was milder compared to the diabetes/impaired glucose metabolism patients. We conclude that in patients with a mutation in the NOTCH3 gene, the co-occurrence of diseases such as type II diabetes/impaired glucose metabolism can cause a multiplication the damages to small blood vessels by modifying/masking the pathogenesis of CADASIL.

Encephalomyelitis associated with rheumatoid arthritis: a case report.

Encephalitis/encephalomyelitis in the course of rheumatoid arthritis (RA) remains a matter of debate. We present a case of a patient with encephalomyelitis associated with RA confirmed with post-mortem neuropathological examination. A 68-year-old woman with a long-standing, seropositive history of RA presented progressive disturbances of consciousness. Magnetic resonance imaging (MRI) of the brain and cervical spine revealed an increase of signal intensity on T2-weighted and fluid attenuated inversion recovery (FLAIR) images with corresponding restricted diffusion involving cerebral peduncles, pons, medulla oblongata, and cervical spinal cord and mild contrast-enhancement of the right cerebral peduncle. Extensive radiological and laboratory testing, including autoantibodies to paraneoplastic anti-neuronal and neuronal cell surface antigens, were all negative except for elevated rheumatoid factor. Cerebrospinal fluid (CSF) analysis revealed moderate pleocytosis with mononuclear cell predominance, mildly increased protein level, and negative viral PCRs, bacterial cultures, flow cytometry, and neuronal surface antibodies. Despite intensive treatment with corticosteroids, antibiotics, antiviral drugs, and intravenous immunoglobulin the patient died after 3 months of hospitalization. Post-mortem neuropathological examination revealed numerous, disseminated, heterochronous ischaemic lesions, rarely with haemorrhagic transformation, predominantly in the brainstem, and widespread, diffuse microglia and T-cell infiltrations with neuronal loss and astrogliosis, most severe in the frontal and temporal lobes. Mild, perivascular lymphocyte T infiltrations involved particularly small and medium-sized vessels and were associated with brainstem ischaemic lesions. The neuropathological picture confirmed diagnosis of encephalomyelitis, which together with the clinical course suggested association with RA. Concluding, encepha-lomyelitis due to RA remains a challenging, controversial entity that needs further research and the establishment of effective diagnostic and treatment guidelines.

Neurogenesis in neurodegenerative diseases in the adult human brain.

Purpose: Adult human brain neurogenesis is the process of cell division, differentiation, and integration of the new neurons in the brain. The neurons that arise in subventricular zone migrate to the olfactory bulb, while the newly formed neurons in the dentate gyrus migrate locally. In adult neurogenesis starting from neural stem cells, in addition to glial neurons astrocytes and oligodendrocytes are also formed. Neurogenesis is regulated by endogenous and exogenous factors influencing the proliferation potential of progeni tor cells and accelerating the rate of development of the dendritic connections of newly formed neurons. Views: The slow, initial process of a developing neurodegenerative disease may have a stimulating effect on neurogenesis. Increased levels of pro-inflammatory factors may contribute to the formation of new neurons. A similar hypothesis seems to be confirmed by data in the literature. The importance of proneurogenic effects during inflammation is shown by proteins secreted by active microglia, mainly CD 47 and CD 55 and interleukin 4 and 10. On the other hand, the unfavorable effect of the inflammatory process in the brain is usually associated with chronic disease in it, when stimulated microglia increase the concentration of cytokines that have a negative effect on neurogenesis. Conclusions: Restoring the balance between dying and emerging neurons is important and offers hope for new therapy directions in the treatment of neurodegenerative diseases. We note common points that could become the target of further research. Attention should be paid to disorders of the calcium metabolism, so important in signal transduction, the state of mitochondria with enzymes involved in the formation of ATP, and the reduction of inflammation in neurogenic regions.

hMTH1 and GPX1 expression in human thyroid tissue is interrelated to prevent oxidative DNA damage.

Oxidative stress (OS) is recognized as disturbance of cellular equilibrium between reactive oxygen species (ROS) formation and their elimination by antioxidant defense systems. One example of ROS-mediated damage is generation of potentially mutagenic DNA precursor, 8-oxodGTP. In human cells genomic 8-oxodGTP incorporation is prevented by the MutT homologue 1 (MTH1 or hMTH1 for human MTH1) protein. It is well established that malignant cells, including thyroid cancer cells, require hMTH1 for maintaining proliferation and cancerous transformation phenotype. Above observations led to the development of hMTH1 inhibitors as novel anticancer therapeutics. In the current study we present extensive analysis of oxidative stress responses determining sensitivity to hMTH1 deficiency in cultured thyroid cells. We observe here that hMTH1 depletion results in downregulation of several glutathione-dependent OS defense system factors, including GPX1 and GCLM, making some of the tested thyroid cell lines highly dependent on glutathione levels. This is evidenced by the increased ROS burden and enhanced proliferation defect after combination of hMTH1 siRNA and glutathione synthesis inhibition. Moreover, due to the lack of data on hMTH1 expression in human thyroid tumor specimens we decided to perform detailed analysis of hMTH1 expression in thyroid tumor and peri-tumoral tissues from human patients. Our results allow us to propose here that anticancer activity of hMTH1 suppression may be boosted by combination with agents modulating glutathione pool, but further studies are necessary to precisely identify backgrounds susceptible to such combination treatment.

Morphological and ultrastructural changes in Herpes simplex encephalomyelitis: an attempt to determinate the etiological factor.

Herpes simplex encephalomyelitis (HSE) is a rare disease with a high mortality rate. Correct diagnosis is established on the basis of the combination of the clinical and investigative features. Unfortunately, precise diagnosis remains difficult due to several clinical similarities and false negative or inconclusive results of diagnostic tests. Here, we present two cases of HSE together with the morphological and ultrastructural picture. The first case was a 45-year-old man with acute symptoms of encephalitis, and the other one was a 28-year-old woman presenting subacute encephalomyelitis. Both cases had negative serologic and molecular results for Herpes simplex in the blood and cerebrospinal fluid. Brain and spinal cord samples taken from both cases were stained typically with histological and immunohistochemical methods and small tissue fragments were examined with the transmission electron microscope (TEM). Microscopic examination confirmed viral encephalomyelitis in both cases. An electron micrograph showed typical intranuclear viral particles inside of damaged neurons, which together with topography of brain and spinal cord changes suggest HHV-1/HHV-2 in the first case and/or HHV-3 in the other case. Thus, morphological and ultrastructural examinations may be a useful tool to set up correct diagnosis and help to determine the pathogenic factor in patients suspected of viral encephalomyelitis.

POLG gene mutation. Clinico-neuropathological study.

We present a female patient with a mutation of the POLG gene (POLG DNA polymerase gamma, catalytic subunit; *174763) in which the clinical course suggested a mitochondrial disease, a neuropathological examination identified the syndrome more closely, and a genetic test confirmed the disease. Apart from the morphological lesions typical of Alpers-Huttenlocher syndrome, rarely observed symmetrical degenerative changes in the accessory olivary nuclei were found. It was unusual in the clinical course of the disease that pancreatitis was diagnosed before symptoms of liver failure appeared.

Elevated serum concentrations of IGF-1 and IGF-1R in patients with thyroid cancers.

BACKGROUND: The rising incidence of thyroid cancer observed in the last few decades requires an improvement in diagnostic tools and management techniques for patients with thyroid nodules. AIMS: The aim of this study was to assess serum concentrations of IGF-1 and IGF-1R in patients diagnosed with thyroid cancers. METHODS: 36 patients diagnosed with papillary thyroid cancer (PTC), 11 subjects with follicular thyroid cancer (FTC), 9 patients with anaplastic thyroid cancer (ATC) and 19 subjects with multinodular nontoxic goiter (MNG) were enrolled to the study. The control group (CG) consisted of 20 healthy volunteers. Blood samples were collected one day before surgery. Serum IGF-1 and IGF-1R concentrations were measured using specific ELISA methods. RESULTS: Significantly higher concentrations of IGF-1 were found in patients with PTC as compared with controls but not that obtained from subjects diagnosed with MNG. The concentration of IGF-1R was significantly elevated in subjects with PTC and ATC as compared with healthy volunteers. Similarly, patients diagnosed with PTC or ATC presented significantly higher serum concentration of IGF-1R in comparison to the MNG group. CONCLUSIONS: Our results show that the IGF-1 - IGF-1R axis plays a significant role in the development of PTC and ATC and imply that serum concentrations of both cytokines may be considered as additional markers for the differentiation of malignancies during the preoperative diagnosis of patients with thyroid gland tumors. These results indicate that IGF-1R serum concentrations allow us to differentiate between MNG and PTC or ATC. Moreover IGF-1R serum values appear to be better predictor of PTC and ATC than IGF-1 concentrations.

Transcription Factor Prospero Homeobox 1 (PROX1) as a Potential Angiogenic Regulator of Follicular Thyroid Cancer Dissemination.

It is well known that Prospero homeobox 1 (PROX1) is a crucial regulator of lymphangiogenesis, that reprograms blood endothelial cells to lymphatic phenotype. However, the role of PROX1 in tumor progression, especially in angiogenesis remains controversial. Herein, we studied the role of PROX1 in angiogenesis in cell lines derived from follicular thyroid cancer (FTC: FTC-133) and squamous cell carcinoma of the thyroid gland (SCT: CGTH-W-1) upon PROX1 knockdown. The genes involved in angiogenesis were selected by RNA-seq, and the impact of PROX1 on vascularization potential was investigated using human umbilical vein endothelial cells (HUVECs) cultured in conditioned medium collected from FTC- or SCT-derived cancer cell lines after PROX1 silencing. The angiogenic phenotype was examined in connection with the analysis of focal adhesion and correlated with fibroblast growth factor 2 (FGF2) levels. Additionally, the expression of selected genes involved in angiogenesis was detected in human FTC tissues. As a result, we demonstrated that PROX1 knockdown resulted in upregulation of factors associated with vascularization, such as metalloproteinases (MMP1 and 3), FGF2, vascular endothelial growth factors C (VEGFC), BAI1 associated protein 2 (BAIAP2), nudix hydrolase 6 (NUDT6), angiopoietin 1 (ANGPT1), and vascular endothelial growth factor receptor 2 (KDR). The observed molecular changes resulted in the enhanced formation of capillary-like structures by HUVECs and upregulated focal adhesion in FTC-133 and CGTH-W-1 cells. The signature of selected angiogenic genes' expression in a series of FTC specimens varied depending on the case. Interestingly, PROX1 and FGF2 showed opposing expression levels in FTC tissues and seven thyroid tumor-derived cell lines. In summary, our data revealed that PROX1 is involved in the spreading of thyroid cancer cells by regulation of angiogenesis.

Dysregulation in IGF-1R, FGFR4 and ßKlotho signaling in patients with medullary thyroid cancer.

BACKGROUND: Medullary thyroid cancer (MTC) is a relatively rare thyroid neoplasm derived from neuroendocrine C cells which secrete calcitonin. αKlotho (αKL) and ßKlotho (ßKL) are transmembrane proteins which modulate different signaling systems, such as endocrine FGFs and IGF1 pathways. Dysregulation of the FGF19/FGFR4/ßKL and IGF-1/IGF-1R/αKL signaling axes has been implicated in the pathogenesis of several cancers. However, their role in the pathogenesis of MTC has not been determined. METHODS: The aim of this study was to assess αKL, ßKL, FGF19, IGF-1, FGFR4, and IGF-1R concentrations in a group of 11 patients with medullary thyroid cancer (MTC). The control group consisted of 20 healthy volunteers. Serum concentrations of these factors were measured using specific ELISA methods. RESULTS: Significantly lower concentrations of ßKL and higher concentrations of FGFR4 and IGF-1R were found in patients with MTC as compared to controls. CONCLUSIONS: Our results indicate that a disrupted signaling pathway for ßKL, FGFR4 and IGF-1R may play a role in the development of medullary thyroid cancers. However, further studies are required to confirm these findings and to use this knowledge in clinical practice.