Publications by authors named "Timea Szekerczes"

We report development and characterization of small non-immunoglobulin affibody affinity proteins directed to the highly glycosylated human carcinoembryonic antigen-related adhesion molecule 5 (CEACAM5, CEA), and their use in immunohistochemical (IHC) analyses of human pancreatic cancer samples and for in vivo tumor imaging. A total of nineteen unique anti-CEA affibodies were identified from large phage display libraries constructed using combinatorial protein engineering of a small 58 amino acid three-helix bundle protein domain. Molecular modeling suggested that all enriched clones share a binding surface with several clustered tryptophan residues interacting with a hydrophobic patch in the N1 domain of CEA centered around a phenylalanine residue.

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Hepatocellular carcinoma (HCC) remains a major global health challenge, particularly in advanced stages where treatments options are limited. Sorafenib, the standard systemic therapy for advanced HCC, offers only modest survival benefits, and is frequently associated with resistance and adverse effects, highlighting the need for improved therapeutic strategies. Se-methylselenocysteine (MSC), a redox-active selenium compound, has demonstrated selective cytotoxicity in cancer cells, particularly when combined with α-ketoacid (Indole-3-pyruvic acid (IPA) and α-Keto-γ-methylthiobutyric acid sodium salt (KMB)).

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Patient-derived tissue culture models are valuable tools to investigate drug effects and targeted treatment approaches. Resected tumor slices cultured ex vivo have recently gained interest in precision medicine, since they reflect the complex microenvironment of cancer tissue. In this study, we examined the treatment response to an internally developed ex vivo tissue culture model from pancreatic ductal adenocarcinoma (PDAC) and in vitro analysis.

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Selenium compounds have pronounced effects on cell growth and proliferation. Nutritional levels induce selenoproteins. However, the antineoplastic effects of supra-nutritional selenium levels are not mediated by selenoproteins.

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The presence of autophagy has been indicated in cholangiocarcinoma (CC), which disease has poor prognosis and limited treatment options. Recently, CC has been classified by anatomical localization as intrahepatic (iCC), perihilar (pCC) and distal (dCC), showing different clinical and molecular characteristics. Thus, our aim was to compare autophagy activity in CC samples resected from different anatomical locations.

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The unique character of selenium compounds, including sodium selenite and Se-methylselenocysteine (MSC), is that they exert cytotoxic effects on neoplastic cells, providing a great potential for treating cancer cells being highly resistant to cytostatic drugs. However, selenium treatment may affect microRNA (miRNA) expression as the pattern of circulating miRNAs changed in a placebo-controlled selenium supplement study. This necessitates exploring possible changes in the expression profiles of miRNAs.

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Cervical cancer is a common malignant tumor worldwide ranking fourth in incidence and mortality among females, which was reduced significantly by cytology screening and human papilloma virus (HPV) DNA testing. The specificity of cytology is high; however, the sensitivity is low, in contrast to the HPV DNA testing. Despite the success of these measures, new biomarkers are still considered to aim increasing sensitivity and specificity of screening and diagnosis.

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Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and - 224) known to be involved in the regulation of autophagy.

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Acetaminophen (APAP) induced hepatotoxicity involves activation of c-Jun amino-terminal kinase (JNK), mitochondrial damage and ER stress. BGP-15, a hydroximic acid derivative, has been reported to have hepatoprotective effects in APAP overdose induced liver damage. Effect of BGP-15 was further investigated on mitochondria in APAP-overdose induced acute liver injury in mice.

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Cholangiocarcinoma (CC) is the second most common tumor of the liver, originating from the biliary system with increasing incidence and mortality worldwide. Several new classifications review the significance of tumor localization, site of origin, proliferation and biomarkers in the intrahepatic, perihilar and distal forms of the lesion. Based on growth pattern mass-forming, periductal-infiltrating, intraductal, undefined and mixed types are differentiated.

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Article Synopsis
  • The study investigates the differences in microRNA (miRNA) expression between focal nodular hyperplasia (FNH), cirrhosis, and hepatocellular carcinoma (HCC) to understand the benign nature of FNH despite histological resemblances to cirrhosis.
  • A total of 106 liver samples were analyzed, revealing varying levels of 14 specific miRNAs, with some being elevated in both FNH and malignant conditions, while others showed decreased levels specifically in FNH.
  • Findings suggest that elevated miR-34a and miR-224 could indicate proliferation in both benign and malignant liver conditions, but altered expression of oncomiRs (like miR-21 and miR-222)
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Several biomarkers are in use to improve the sensitivity and specificity of cervical cancer screening. Previously, increased expression of tight junction protein claudin-1 (CLDN1) was detected in premalignant and malignant cervical lesions and applied for cytology screening. To improve the specificity, a double immunoreaction with CLDN1/Ki67 was developed in the recent study.

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Several immunochemistry tests are used for triaging human papilloma virus (HPV) and cytology positive cases in cervical cancer screening and as an adjunct test to diagnose cervical cancer. Claudin-1 (CLDN1) protein is a major component of the tight junction, shown to have altered expression in cervical cancer. In this study, value of CLDN1 was analysed as a screening and triage immunochemistry test compared to cytology and HPV testing.

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