Andelko HrzenjakMedical University of Graz · Clinical Department of Pulmonology
Andelko Hrzenjak
PhD
About
99
Publications
8,861
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
3,038
Citations
Introduction
Additional affiliations
May 1995 - March 2003
Publications
Publications (99)
Serine and glycine give rise to important building blocks in proliferating cells. Both amino acids are either synthesized de novo or taken up from the extracellular space. In lung cancer, serine synthesis gene expression is variable, yet, expression of the initial enzyme, phosphoglycerate dehydrogenase (PHGDH), was found to be associated with poor...
Metformin is the most commonly prescribed glucose-lowering drug for the treatment of type 2 diabetes. The aim of this study was to investigate whether metformin is capable of impeding the oxidation of LDL, a crucial step in the development of endothelial dysfunction and atherosclerosis. LDL was oxidized by addition of CuCl2 in the presence of incre...
People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of...
Background:
The potential of microRNAs (miRNAs) as molecular tumor biomarkers for early diagnosis and prognosis in lung cancer is still unclear.
Objective:
To analyze expression of miRNAs in A549 lung adenocarcinoma (LUAD) cells and in primary, non-malignant bronchial epithelial (BE) cells from healthy donors. To analyze the most prominently der...
Lung cancer belongs to the most frequent and deadliest cancer types worldwide, non-small cell lung carcinoma (NSCLC) being the most frequent type. Development of chemoresistance in NSCLC patients is common and responsible for bad outcome. Curcuminoids are naturally occurring substances with prominent cytotoxic effects in different cancer cells. Her...
Osteosarcoma (OS) is the most common type of bone tumor, and has limited therapy options. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has striking anti-tumor effects in various tumors. Here, we investigated molecular mechanisms that mediate anti-tumor effects of 15d-PGJ2 in different OS cell lines. Human U2-OS and Saos-2 cells were treated with 15d...
Cancer cells frequently lack nutrients like glucose, due to insufficient vascular networks. Mitochondrial phosphoenolpyruvate carboxykinase, PCK2, has recently been found to mediate partial gluconeogenesis and hence anabolic metabolism in glucose starved cancer cells. Here we show that PCK2 acts as a regulator of mitochondrial respiration and maint...
Endothelial lipase (EL) is a strong modulator of the high-density lipoprotein (HDL) structure, composition, and function. Here, we examined the impact of EL on HDL paraoxonase 1 (PON1) content and arylesterase (AE) activity in vitro and in vivo. The incubation of HDL with EL-overexpressing HepG2 cells decreased HDL size, PON1 content, and AE activi...
In cancer cells, metabolic pathways are reprogrammed to promote cell proliferation and growth. While the rewiring of central biosynthetic pathways is being extensively studied, the dynamics of phospholipids in cancer cells are still poorly understood. In our study, we sought to evaluate de novo biosynthesis of glycerophospholipids (GPLs) in ex vivo...
Cancer cells frequently lack nutrients like glucose, due to insufficient vascular networks. A decrease of extracellular glucose is accompanied by enhanced mitochondrial respiration in cancer cells, which promotes the formation of potentially harmful reactive oxygen species (ROS). Here we show that a gluconeogenesis enzyme, mitochondrial phosphoenol...
Inhibition of glycolysis has been considered as a therapeutic approach in aggressive cancers including lung cancer. Abbreviated gluconeogenesis, mediated by phosphoenolpyruvate carboxykinase (PEPCK), was recently discovered to partially circumvent the need for glycolysis in lung cancer cells. However, the interplay of glycolysis and gluconeogenesis...
Lung cancer is one of the deadliest cancers worldwide. Late diagnosis at an advanced, inoperable stage makes chemotherapy a treatment of choice, yet, with low response rates. The hedgehog signaling pathway (HHSP) is often reactivated in cancer. We identified miR-182-5p as a regulator of GLI2, a transcriptional regulator of the HHSP, and explored th...
Rationale
Our systematic analysis of anion channels and transporters in idiopathic pulmonary arterial hypertension (IPAH) showed marked upregulation of the Cl ⁻ channel TMEM16A gene.
Objective
We hypothesised that TMEM16A overexpression might represent a novel vicious circle in the molecular pathways causing PAH.
Methods and results
We investigat...
Significance
Phosphoenolpyruvate carboxykinase (PEPCK) has a unique position in cell metabolism by allowing the flexible use of nutrients for anabolic biosynthetic reactions. PEPCK activity has just recently been described in cancer cells. It has been shown to promote cancer cell survival under nutrient deprivation, a typical feature in solid cance...
Lung cancer patients have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (Epo) has consistently been shown to reduce the need for blood transfusions and to increase hemoglobin levels in lung cancer patients with chemotherapy-induced anemia. However, clinical and preclinical studies have...
Endothelial lipase (EL) is a potent modulator of the structural and functional properties of HDL. Impact of EL on cholesterol efflux capacity (CEC) of serum and isolated HDL is not well understood and apparently contradictory data were published. Here, we systematically examined the impact of EL on composition and CEC of serum and isolated HDL, in...
Objectives
Lung cancer is the leading cause of cancer death worldwide. Like in all solid tumors, hypoxia is common in lung cancer and contributes to apoptosis, and thus chemotherapy resistance. However, the underlying mechanisms are not entirely clear. TR3 (NR4A1, Nur77) is an orphan nuclear receptor that induces apoptosis and may mediate chemother...
Endometrial stromal sarcomas (ESSs) belong to the rarest uterine malignancies (prevalence category <1-9/1,000,000). According to the new 2014 World Health Organisation (WHO) classification, they are separated into four categories; benign endometrial stromal nodules (ESNs), low grade endometrial stromal sarcomas (LG-ESSs), high-grade endometrial str...
Lung cancer is the leading cause of cancer deaths worldwide; survival times are poor despite therapy. The role of the two-pore domain K+ (K2P) channel TASK-1 (KCNK3) in lung cancer is at present unknown. We found that TASK-1 is expressed in non-small cell lung cancer (NSCLC) cell lines at variable levels. In a highly TASK-1 expressing NSCLC cell li...
FACS analysis of caspase 3 activity in H358 cells.
H358 cells were incubated under the respective conditions for 72 hours and cells with caspase 3 activity were detected by FACS analysis. Left: representative histogram, M1 indicates apoptotic cells. Right: gating conditions.
(PDF)
FACS analysis of caspase 3 activity and EdU incorporation in A549 cells.
(A) A549 cells were incubated under the respective conditions for 72 hours and cells with caspase 3 activity were detected by FACS analysis. Left: representative histogram, M1 indicates apoptotic cells. Right: gating conditions. (B) EdU assay in A549 cells. Left: representativ...
Introduction: Lung cancer patients have the highest incidence of anaemia among patients with solid tumours. The use of recombinant human erythropoietin (rHuEpo) has consistently been shown to reduce the need of blood transfusions and increase the haemoglobin level in lung cancer patients with chemotherapy-induced anaemia. However, clinical and prec...
With more than 80% of all diagnosed lung cancer cases, non-small cell lung cancer (NSCLC) remains the leading cause of cancer death worldwide. Exact diagnosis is mostly very late and advanced-stage NSCLCs are inoperable at admission. Tailored therapies with tyrosine kinase inhibitors are only available for a minority of patients. Thus, chemotherapy...
Lung cancer is one of the most frequent cancer types and the leading cause of cancer death worldwide. Cisplatin is a widely used chemotherapeutic for non-small cell lung carcinoma (NSCLC), however, its positive effects are diminished under hypoxia. We wanted to determine if co-treatment with cisplatin and histone deacetalyse (HDAC) inhibitor panobi...
Zhang et al. (1) make a valuable contribution to the field of cancer metabolism, showing that the tumor suppressor p53 down-regulates the gluconeogenic key enzyme phosphoenolpyruvate carboxykinase (PEPCK, PCK1) via histone deacetylase sirtuin 6. The authors conclude that inhibition of gluconeogenesis may contribute to the tumor-suppressive function...
Cancer cells are reprogrammed to utilize glycolysis at high rates, which provides metabolic precursors for cell growth. Consequently, glucose levels may decrease substantially in underperfused tumor areas. Gluconeogenesis results in the generation of glucose from smaller carbon substrates such as lactate and amino acids. The key gluconeogenic enzym...
Hypoxia-induced genes are potential targets in cancer therapy. Responses to hypoxia have been extensively studied in vitro, however, they may differ in vivo due to the specific tumor microenvironment. In this study gene expression profiles were obtained from fresh human lung cancer tissue fragments cultured ex vivo under different oxygen concentrat...
The potassium channel TWIK-related acid sensitive potassium (TASK)-1 channel, together with other potassium channels, controls the low resting tone of pulmonary arteries. The Src family tyrosine kinase (SrcTK) may control potassium channel function in human pulmonary artery smooth muscle cells (hPASMCs) in response to changes in oxygen tension and...
Exposure of mice to chronic hypoxia is one of the most often used animal models to study pulmonary hypertension. Hypoxia exposure leads to vascular remodeling and muscularization of the small parenchymal vessels in the lung. Due to the anatomical differences between mice and humans, it is not possible to determine whether the remodeled vessels orig...
Hypoxia frequently occurs in solid tumors and is known to contribute to chemotherapy resistance. However, the mechanisms leading to chemotherapy resistance are not entirely known. We investigated hypoxia-induced resistance to cisplatin in NSCLC cell lines. We show that chronic moderate hypoxia induced resistance to cisplatin in NSCLC cells without...
Previously we identified palmitoyl-lysophosphatidylcholine (LPC 16:0), as well as linoleoyl-, arachidonoyl- and oleoyl-LPC (LPC 18:2, 20:4 and 18:1) as the most prominent LPC species generated by the action of endothelial lipase (EL) on high-density lipoprotein (HDL). In the present study, the impact of EL and EL-generated LPC on interleukin-8 (IL-...
Introduction: Within the last decade, intensive research on the influence of erythropoietin (Epo) on the tumour biology unveiled the growth factor Epo as a possible stimulator of growth, differentiation, and survival even of non-haematopoietic cells acting via its receptor (EpoR). Epo is considered to be a therapeutic option in tumour patients suff...
Previously we identified palmitoyl-lysophosphatidylcholine (16:0 LPC), linoleoyl-LPC (18:2 LPC), arachidonoyl-LPC (20:4 LPC), and oleoyl-LPC (18:1 LPC) as the most prominent LPC species generated by the action of endothelial lipase (EL) on high-density lipoprotein. In the present study, the impact of those LPC on prostacyclin (PGI(2)) production wa...
Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC) inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat) on MES-SA uterine sarcoma cells in vitro and in vi...
Recent observations link myeloperoxidase (MPO) activation to neurodegeneration. In multiple sclerosis MPO is present in areas of active demyelination where the potent oxidant hypochlorous acid (HOCl), formed by MPO from H(2)O(2) and chloride ions, could oxidatively damage myelin-associated lipids. The purpose of this study was (i) to characterize r...
Advanced oxidation protein products (AOPPs) are carried by oxidized plasma proteins, especially albumin and accumulate in subjects with renal disease and coronary artery disease. AOPPs represent an excellent novel marker of oxidative stress and their roles in the development of cardiovascular disease might be of great importance. Here, we show that...
Endometrial stromal sarcomas are rare and molecular mechanisms involved in their pathogenesis are poorly understood. Covalent modifications of histone proteins, in particular de/acetylation of lysine residues, play an important role in the regulation of gene transcription in normal and neoplastic cells, but there are only limited data about these p...
Genetic abnormalities in microenvironmental tissues with subsequent alterations of reciprocal interactions between epithelial and mesenchymal cells play a key role in the breast carcinogenesis. Although a few reports have demonstrated abnormal fibroblastic functions in normal-appearing fibroblasts taken from the skins of breast cancer patients, the...
Anaplastic large cell lymphomas (ALCLs) are highly proliferating tumors that commonly express the AP-1 transcription factor JunB. ALK fusions occur in approximately 50% of ALCLs, and among these, 80% have the t(2;5) translocation with NPM-ALK expression. We report greater activity of JunB in NPM-ALK-positive than in NPM-ALK-negative ALCLs. Specific...
The nucleophosmin (NPM) - anaplastic lymphoma kinase (ALK) fusion protein, which is the product of the balanced chromosomal rearrangement t(2;5)(p23;q35), occurs in about 50% of nodal anaplastic large cell lymphoma (ALCL). Expression of this fusion kinase results in neoplastic transformation by modulating multiple intracellular signaling molecules,...
High expression of the tumor necrosis factor receptor CD30 and the AP-1 transcription factor JunB are the hallmark of anaplastic large cell lymphoma (ALCL). In contrast to the prototypic AP-1 factor c-Jun, JunB exerts an antioncogenic function in most cell types. Its functional role in ALCL remains uncertain. In about 50% of nodal ALCL the balanced...
Covalent modifications of histone proteins, in particular deacetylation of lysine residues, are important for the regulation of gene transcription both in normal and malignant cells. These processes are controlled by histone acetyltransferases and histone deacetylases (HDAC) and have up to now not been described in solid mesenchymal tumors. The pre...
Up to 50% of patients with ovarian granulosa cell tumors (GCTs) will develop recurrences; some of these recurrences can be seen as late as 30 years following the initial surgical treatment. Combined chemotherapy and radiotherapy are currently used for patients with advanced or recurrent disease. The aim of this study was to investigate the possible...
The placenta comprises a highly specialized trophoblast layer, which arises from the embryo and differentiates during embryonic development to perform specialized functions, e.g., synthesis of pregnancy-associated hormones, growth factors and cytokines. As there is no evidence of maternal acute-phase protein transplacental transfer and trophoblast...
Endometrial stromal tumors are rare uterine neoplasms including benign stromal nodules, low-grade endometrial stromal sarcomas (ESS), and undifferentiated endometrial sarcomas (UES), the latter representing the most aggressive form. Morphological characteristics and cytogenetic abnormalities are heterogeneous, making diagnosis difficult. Recently,...
Endometrial stromal tumors are rare uterine neoplasms including benign stromal nodules, low-grade endometrial stromal sarcomas (ESS), and undifferentiated endometrial sarcomas (UES), the latter representing the most aggressive form. Morphological characteristics and cytogenetic abnormalities are heterogeneous, making diagnosis difficult. Recently,...
Mature endothelial lipase (EL) is a 68 kDa glycoprotein. In HepG2 cells infected with adenovirus encoding human EL, the mature EL was detectable in the cell lysates and heparin-releasable fractions. In contrast, cell media of these cells contained two EL fragments: an N-terminal 40 kDa fragment and a C-terminal 28 kDa fragment. N-terminal protein s...
We previously reported that scavenger receptor class B, type I (SR-BI) mediates uptake of lipoprotein-associated cholesteryl ester and Vitamin E by porcine brain capillary endothelial cells (pBCECs). In the present study we investigated whether SR-BI is capable of mediating phosphatidylcholine (PC) uptake by pBCECs from low- and high density lipopr...
Endometrial stromal sarcomas are rare uterine tumours. Whereas the histology and immunohistochemistry of these tumours are well documented, almost nothing is known about the molecular mechanisms involved in their pathogenesis. To characterize the genes altered in these malignancies, a genome-wide cDNA library was generated by suppression subtractiv...
Alpha-tocopheryl-succinate (alphaTS) is a synthetic, anti-neoplastic derivative of alpha-tocopherol. Here we studied the effects of free and high-density lipoprotein subclass 3 (HDL3)-associated alphaTS on the growth of human (A549) and mouse Lewis (LL2) lung carcinoma cells. Both free and HDL3-associated alphaTS inhibited A549 growth in a time- an...
Background: Little is known of the catabolism of Lp(a). Although Lp(a) has been found to bind in vitro to numerous receptors, the relevance of these pathways has not been documented in vivo. Here, we investigated the involvement of asialo glycoprotein receptors (ASGPR) in the catabolism of Lp(a). Methods: Lp(a) was isolated from donors with various...
Lipoprotein lipase (LPL) is the only known enzyme in the capillary endothelium of peripheral tissues that hydrolizes plasma triglycerides and provides fatty acids (FAs) for their subsequent tissue uptake. Previously, we demonstrated that mice that express LPL exclusively in muscle develop essentially normal fat mass despite the absence of LPL and t...