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This work investigated the potential of a novel formulation of eye drops containing a non-steroidal anti-inflammatory drug—choline salicylate (CS)—and hyaluronic acid (HA). Thus, these drops may exert both anti-inflammatory and regenerative activity. The experiment was conducted through the careful characterization of physicochemical properties, stability, and quality of eye drops. Moreover, microbiological analysis, as well as penetration and cytotoxic studies, were performed. The UV, HPLC-UV, and HPLC-MS/MS methods were used to determine the purity and stability of CS. The penetration rate of CS was assessed using a hydrophilic membrane and ex vivo porcine cornea model. Additionally, the cytotoxic effects were evaluated using the SIRC cell line. The interaction between HA and CS was tested using size-exclusion chromatography and IR spectrophotometry. As a result, HA increased the viscosity of the drops, which prolonged their contact with the ocular surface, thus ensuring more effective penetration of CS into the corneal structure. After long-term storage, an interaction in the pharmaceutical phase between CS and HA was observed. However, this interaction did not affect the viability of rabbit corneal cells. Our findings showed that eye drops with CS and HA, stored at 2–8 °C in light-protected conditions, met the criteria of stability and safety.
Katarzyna Barbara Wróblewska; Bartłomiej Milanowski; Małgorzata Kucińska; Szymon Plewa; Jolanta Długaszewska; Izabela Muszalska-Kolos. Novel Formulation of Eye Drops Containing Choline Salicylate and Hyaluronic Acid: Stability, Permeability, and Cytotoxicity Studies Using Alternative Ex Vivo and In Vitro Models. Pharmaceuticals 2021, 14, 849 .
AMA StyleKatarzyna Barbara Wróblewska, Bartłomiej Milanowski, Małgorzata Kucińska, Szymon Plewa, Jolanta Długaszewska, Izabela Muszalska-Kolos. Novel Formulation of Eye Drops Containing Choline Salicylate and Hyaluronic Acid: Stability, Permeability, and Cytotoxicity Studies Using Alternative Ex Vivo and In Vitro Models. Pharmaceuticals. 2021; 14 (9):849.
Chicago/Turabian StyleKatarzyna Barbara Wróblewska; Bartłomiej Milanowski; Małgorzata Kucińska; Szymon Plewa; Jolanta Długaszewska; Izabela Muszalska-Kolos. 2021. "Novel Formulation of Eye Drops Containing Choline Salicylate and Hyaluronic Acid: Stability, Permeability, and Cytotoxicity Studies Using Alternative Ex Vivo and In Vitro Models." Pharmaceuticals 14, no. 9: 849.
Gynecological and breast cancers still remain a significant health problem worldwide. Diagnostic methods are not sensitive and specific enough to detect the disease at an early stage. During carcinogenesis and tumor progression, the cellular need for DNA and protein synthesis increases leading to changes in the levels of amino acids. An important role of amino acids in many biological pathways, including biosynthesis of proteins, nucleic acids, enzymes, etc., which serve as an energy source and maintain redox balance, has been highlighted in many research articles. The aim of this review is a detailed analysis of the literature on metabolomic studies of gynecology and breast cancers with particular emphasis on alterations in free amino acid profiles. The work includes a brief overview of the metabolomic methodology and types of biological samples used in the studies. Special attention was paid to the possible role of selected amino acids in the carcinogenesis, especially proline and amino acids related to its metabolism. There is a clear need for further research and multiple external validation studies to establish the role of amino acid profiling in diagnosing gynecological and breast cancers.
Dagmara Pietkiewicz; Agnieszka Klupczynska-Gabryszak; Szymon Plewa; Magdalena Misiura; Agnieszka Horala; Wojciech Miltyk; Ewa Nowak-Markwitz; Zenon Kokot; Jan Matysiak. Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review. Pharmaceuticals 2021, 14, 731 .
AMA StyleDagmara Pietkiewicz, Agnieszka Klupczynska-Gabryszak, Szymon Plewa, Magdalena Misiura, Agnieszka Horala, Wojciech Miltyk, Ewa Nowak-Markwitz, Zenon Kokot, Jan Matysiak. Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review. Pharmaceuticals. 2021; 14 (8):731.
Chicago/Turabian StyleDagmara Pietkiewicz; Agnieszka Klupczynska-Gabryszak; Szymon Plewa; Magdalena Misiura; Agnieszka Horala; Wojciech Miltyk; Ewa Nowak-Markwitz; Zenon Kokot; Jan Matysiak. 2021. "Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review." Pharmaceuticals 14, no. 8: 731.
Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder, affecting 5–10% of women of reproductive age. It results from complex environmental factors, genetic predisposition, hyperinsulinemia, hormonal imbalance, neuroendocrine abnormalities, chronic inflammation, and autoimmune disorders. PCOS impacts menstrual regularities, fertility, and dermatological complications, and may induce metabolic disturbances, diabetes, and coronary heart disease. Comprehensive metabolic profiling of patients with PCOS may be a big step in understanding and treating the disease. The study aimed to search for potential differences in metabolites concentrations among women with PCOS according to different body mass index (BMI) in comparison to healthy controls. We used broad-spectrum targeted metabolomics to evaluate metabolites’ serum concentrations in PCOS patients and compared them with healthy controls. The measurements were performed using high-performance liquid chromatography coupled with the triple quadrupole tandem mass spectrometry technique, which has highly selective multiple reaction monitoring modes. The main differences were found in glycerophospholipid concentrations, with no specific tendency to up-or down-regulation. Insulin resistance and elevated body weight influence acylcarnitine C2 levels more than PCOS itself. Sphingomyelin (SM) C18:1 should be more intensively observed and examined in future studies and maybe serve as one of the PCOS biomarkers. No significant correlations were observed between anthropometric and hormonal parameters and metabolome results.
Katarzyna Ożegowska; Szymon Plewa; Urszula Mantaj; Leszek Pawelczyk; Jan Matysiak. Serum Metabolomics in PCOS Women with Different Body Mass Index. Journal of Clinical Medicine 2021, 10, 2811 .
AMA StyleKatarzyna Ożegowska, Szymon Plewa, Urszula Mantaj, Leszek Pawelczyk, Jan Matysiak. Serum Metabolomics in PCOS Women with Different Body Mass Index. Journal of Clinical Medicine. 2021; 10 (13):2811.
Chicago/Turabian StyleKatarzyna Ożegowska; Szymon Plewa; Urszula Mantaj; Leszek Pawelczyk; Jan Matysiak. 2021. "Serum Metabolomics in PCOS Women with Different Body Mass Index." Journal of Clinical Medicine 10, no. 13: 2811.
Proper preoperative ovarian cancer (OC) diagnosis remains challenging. Serum free amino acid (SFAA) profiles were investigated to identify potential novel biomarkers of OC and assess their performance in ovarian tumor differential diagnosis. Serum samples were divided based on the histopathological result: epithelial OC (n = 38), borderline ovarian tumors (n = 6), and benign ovarian tumors (BOTs) (n = 62). SFAA profiles were evaluated using aTRAQ methodology based on high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Levels of eleven amino acids significantly differed between OC+borderline and BOTs. The highest area under the receiver operating characteristic curve (AUC of ROC) (0.787) was obtained for histidine. Cystine and histidine were identified as best single markers for early stage OC/BOT and type I OC. For advanced stage OC, seven amino acids differed significantly between the groups and citrulline obtained the best AUC of 0.807. Between type II OC and BOTs, eight amino acids differed significantly and the highest AUC of 0.798 was achieved by histidine and citrulline (AUC of 0.778). Histidine was identified as a potential new biomarker in differential diagnosis of ovarian tumors. Adding histidine to a multimarker panel together with CA125 and HE4 improved the differential diagnosis between OC and BOTs.
Agnieszka Horala; Szymon Plewa; Pawel Derezinski; Agnieszka Klupczynska; Jan Matysiak; Ewa Nowak-Markwitz; Zenon Kokot. Serum Free Amino Acid Profiling in Differential Diagnosis of Ovarian Tumors—A Comparative Study with Review of the Literature. International Journal of Environmental Research and Public Health 2021, 18, 2167 .
AMA StyleAgnieszka Horala, Szymon Plewa, Pawel Derezinski, Agnieszka Klupczynska, Jan Matysiak, Ewa Nowak-Markwitz, Zenon Kokot. Serum Free Amino Acid Profiling in Differential Diagnosis of Ovarian Tumors—A Comparative Study with Review of the Literature. International Journal of Environmental Research and Public Health. 2021; 18 (4):2167.
Chicago/Turabian StyleAgnieszka Horala; Szymon Plewa; Pawel Derezinski; Agnieszka Klupczynska; Jan Matysiak; Ewa Nowak-Markwitz; Zenon Kokot. 2021. "Serum Free Amino Acid Profiling in Differential Diagnosis of Ovarian Tumors—A Comparative Study with Review of the Literature." International Journal of Environmental Research and Public Health 18, no. 4: 2167.
This study presents the use of matrix-assisted laser desorption and ionization mass spectrometry imaging (MALDI-MSI) directly on the tissue of two ovarian tumors that often present a diagnostic challenge, a low-grade serous borderline ovarian tumor and ovarian fibrothecoma. Different spatial distribution of m/z values within the tissue samples was observed, and regiospecific peaks were identified. Among the 106 peaks in the borderline ovarian tumor five, regiospecific peaks (m/z: 2861.35; 2775.79; 3368.34; 3438.43; 4936.37) were selected using FlexImaging software. Subsequently, the distribution of those selected peaks was visualized on the fibrothecoma tissue section, which demonstrated the differences in the tissue homo-/heterogeneous structure of both tumors. The comparison with the histopathological staining of the ovarian borderline tumor tissue section, obtained during serial sectioning, showed a close correlation of the molecular map with the morphological and histopathological features of the tissue and allowed the identification of different tissue types within the sample. This study highlights the potential significance of MSI in enabling morphological characterization of ovarian tumors as well as correct diagnosis and further prognosis than thus far seen in the literature. Osteopontin, tropomyosin and orosomucoid are only a couple of the molecules investigated using MALDI-MSI in ovarian cancer research. This study, in line with the available literature, proves the potential of MALDI-MSI to overcome the current limitations of classic histopathological examination giving a more in-depth insight into the tissue structure and thus lead to the more accurate differential diagnosis of ovarian tumors, especially in the most challenging cases.
Dagmara Pietkiewicz; Agnieszka Horała; Szymon Plewa; Piotr Jasiński; Ewa Nowak-Markwitz; Zenon J. Kokot; Jan Matysiak. MALDI-MSI—A Step Forward in Overcoming the Diagnostic Challenges in Ovarian Tumors. International Journal of Environmental Research and Public Health 2020, 17, 7564 .
AMA StyleDagmara Pietkiewicz, Agnieszka Horała, Szymon Plewa, Piotr Jasiński, Ewa Nowak-Markwitz, Zenon J. Kokot, Jan Matysiak. MALDI-MSI—A Step Forward in Overcoming the Diagnostic Challenges in Ovarian Tumors. International Journal of Environmental Research and Public Health. 2020; 17 (20):7564.
Chicago/Turabian StyleDagmara Pietkiewicz; Agnieszka Horała; Szymon Plewa; Piotr Jasiński; Ewa Nowak-Markwitz; Zenon J. Kokot; Jan Matysiak. 2020. "MALDI-MSI—A Step Forward in Overcoming the Diagnostic Challenges in Ovarian Tumors." International Journal of Environmental Research and Public Health 17, no. 20: 7564.
The 3,9-dihydro-3-[(2-hydroxyethoxy)methyl]-6-(4-methoxyphenyl)-9-oxo-5H-imidazo[1,2-a]–purine (6-(4-MeOPh)-TACV) was selected to assess the enzymatic stability of the tricyclic acyclovir derivatives from the imidazo[1,2-a]-purine group. The parent compound and its esters (acetyl, isobutyryl, pivaloyl, nicotinic, ethoxycarbonyl) were subjected to kinetic studies and compared with the stability of analogous acyclovir (ACV) esters. The enzymatic hydrolysis was observed in vitro in a medium of 80% human plasma in the absence and presence of porcine liver esterase (PLE). The tests were carried out at 37 °C. To determine the kinetic parameters (kobs., t0.5) of the observed reaction, the validated HPLC-UV method in the reversed phase was used. The HPLC-MS/MS method was used to identify the degradation products under the tested conditions. In summary, it was found that 6-(4-MeOPh)-TACV esters are more susceptible to esterase metabolism than ACV esters. It was confirmed by HPLC-MS/MS that in the plasma, the main product of their hydrolysis is 6-(4-MeOPh)-TACV and not ACV, which confirms that their antiviral activity observed in vitro does not result from ring degradation.
Izabela Muszalska-Kolos; Monika A. Lesniewska-Kowiel; Szymon Plewa; Agnieszka Klupczyńska. Tricyclic Derivative of Acyclovir and Its Esters in Relation to the Esters of Acyclovir Enzymatic Stability: Enzymatic Stability Study. Molecules 2020, 25, 2156 .
AMA StyleIzabela Muszalska-Kolos, Monika A. Lesniewska-Kowiel, Szymon Plewa, Agnieszka Klupczyńska. Tricyclic Derivative of Acyclovir and Its Esters in Relation to the Esters of Acyclovir Enzymatic Stability: Enzymatic Stability Study. Molecules. 2020; 25 (9):2156.
Chicago/Turabian StyleIzabela Muszalska-Kolos; Monika A. Lesniewska-Kowiel; Szymon Plewa; Agnieszka Klupczyńska. 2020. "Tricyclic Derivative of Acyclovir and Its Esters in Relation to the Esters of Acyclovir Enzymatic Stability: Enzymatic Stability Study." Molecules 25, no. 9: 2156.
Choline salicylate (CS) as a derivative of acetylsalicylic acid is commonly used in different drug forms. In medicine, it is applied topically to inflammation of the oral cavity mucosa and in laryngology. However, this substance in the form of an ionic liquid has not been investigated enough. There are no literature studies on stability tests constituting a stage of pre-formulation research. HPLC (Nucleosil C18, 4.6 × 150 mm, 5 μm; methanol-water-acetic acid 60:40:1, 230 nm or 270 nm) and UV (276 nm) methods for the determination of CS in 2% (g/mL) aqueous solutions were developed. Under stress conditions, CS susceptibility to hydrolytic degradation in aqueous medium, hydrochloric acid, sodium hydroxide, and hydrogen peroxide, and the effect of light on the stability of CS solutions were studied with HPLC analysis. The degradation degree of CS and the purity of the solutions were also tested. Choline salicylate has been qualified as practically stable in neutral and acid media, stable in an alkaline medium, very stable in an oxidizing environment, and photolabile in solution. The HPLC-MS/MS method was used to identify 2,3- and 2,5-dihydroxybenzoic acids as degradation products of CS under the tested conditions.
Katarzyna B. Wróblewska; Szymon Plewa; Paweł Dereziński; Izabela Muszalska-Kolos. Choline Salicylate Analysis: Chemical Stability and Degradation Product Identification. Molecules 2019, 25, 51 .
AMA StyleKatarzyna B. Wróblewska, Szymon Plewa, Paweł Dereziński, Izabela Muszalska-Kolos. Choline Salicylate Analysis: Chemical Stability and Degradation Product Identification. Molecules. 2019; 25 (1):51.
Chicago/Turabian StyleKatarzyna B. Wróblewska; Szymon Plewa; Paweł Dereziński; Izabela Muszalska-Kolos. 2019. "Choline Salicylate Analysis: Chemical Stability and Degradation Product Identification." Molecules 25, no. 1: 51.
The ability of early lung cancer diagnosis is an unmet need in clinical practice. Lung cancer metabolomic analyses conducted so far have demonstrated several abnormalities in cancer lipid profile providing a rationale for further study of blood lipidome of the patients. In the present research, we performed a targeted lipidome screening to select molecules that show promise for early lung cancer detection. The study was conducted on serum samples collected from newly diagnosed, stage I non-small cell lung cancer (NSCLC) patients and non-cancer controls. A high-throughput mass spectrometry-based platform with confirmed interlaboratory reproducibility was used. The analyzed profile consisted of acylcarnitines, sphingomyelins, phosphatidylcholines and lysophosphatidylcholines. Among the assayed lipid species, the significant differences between NSCLC and non-cancer subjects were observed in the group of phosphatidylcholines (PC) and lysophosphatidylcholines (lysoPC), especially in the levels of lysoPC a C26:0; lysoPC a C26:1; PC aa C42:4; and PC aa C34:4. The metabolites mentioned above were used to create a multivariate classification model, which reliability was proved by permutation tests as well as external validation. Our study indicated choline-containing phospholipids as potential lung cancer markers. Further investigations of phospholipidome are crucial to better describe the shifts in metabolite composition occurring in lung cancer patients.
Agnieszka Klupczynska; Szymon Plewa; Mariusz Kasprzyk; Wojciech Dyszkiewicz; Zenon Kokot; Jan Matysiak. Serum lipidome screening in patients with stage I non-small cell lung cancer. Clinical and Experimental Medicine 2019, 19, 505 -513.
AMA StyleAgnieszka Klupczynska, Szymon Plewa, Mariusz Kasprzyk, Wojciech Dyszkiewicz, Zenon Kokot, Jan Matysiak. Serum lipidome screening in patients with stage I non-small cell lung cancer. Clinical and Experimental Medicine. 2019; 19 (4):505-513.
Chicago/Turabian StyleAgnieszka Klupczynska; Szymon Plewa; Mariusz Kasprzyk; Wojciech Dyszkiewicz; Zenon Kokot; Jan Matysiak. 2019. "Serum lipidome screening in patients with stage I non-small cell lung cancer." Clinical and Experimental Medicine 19, no. 4: 505-513.
Background Lapatinib is a small-molecule tyrosine kinase inhibitor of human epidermal receptor 2 (HER2) and EGFR that has currently been approved for the treatment of HER2-positive advanced and metastatic breast cancer (BC). The ATP-binding cassette (ABC) family of transporters includes P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2), which substantially restrict the penetration of drugs, including chemotherapeutics, through the blood-brain barrier and blood-cerebrospinal fluid barrier. The aim of this study was to investigate the effects of elacridar, an ABCB1 and ABCG2 inhibitor, on the brain and cerebrospinal fluid uptake of lapatinib. Methods Rats were divided into two groups: one group received 5 mg/kg elacridar and 100 mg/kg lapatinib (an experimental group), and the other group received 100 mg/kg lapatinib (a control group). Lapatinib concentrations in the blood plasma (BP), cerebrospinal fluid (CSF) and brain tissue (BT) were measured by liquid chromatography coupled with tandem mass spectrometry. Results Elacridar significantly increased lapatinib penetration into the CSF and BT (Cmax increase of 136.4% and 54.7% and AUC0-∞ increase of 53.7% and 86.5%, respectively). The Cmax of lapatinib in BP was similar in both experimental groups (3057.5 vs. 3257.5 ng/mL, respectively). Conclusion This study showed that elacridar influenced the pharmacokinetics of lapatinib. The inhibition of ABCB1 and ABCG2 transporters by elacridar substantially enhanced the penetration of lapatinib into the CSF and BT. The blocking of protein transporters could become indispensable in the treatment of patients with breast cancer and brain metastases.
Agnieszka Karbownik; Katarzyna Sobańska; Włodzimierz Płotek; Tomasz Grabowski; Agnieszka Klupczynska; Szymon Plewa; Edmund Grzeskowiak; Edyta Szalek. The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid. Investigational New Drugs 2019, 38, 574 -583.
AMA StyleAgnieszka Karbownik, Katarzyna Sobańska, Włodzimierz Płotek, Tomasz Grabowski, Agnieszka Klupczynska, Szymon Plewa, Edmund Grzeskowiak, Edyta Szalek. The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid. Investigational New Drugs. 2019; 38 (3):574-583.
Chicago/Turabian StyleAgnieszka Karbownik; Katarzyna Sobańska; Włodzimierz Płotek; Tomasz Grabowski; Agnieszka Klupczynska; Szymon Plewa; Edmund Grzeskowiak; Edyta Szalek. 2019. "The influence of the coadministration of the p-glycoprotein modulator elacridar on the pharmacokinetics of lapatinib and its distribution in the brain and cerebrospinal fluid." Investigational New Drugs 38, no. 3: 574-583.
To comprehensively characterize honeybee venom, royal jelly, propolis, and pollen, by applying advanced analytical and bioinformatics methodologies. Honeybee products (HBP) contain many bioactive components with both beneficial and harmful effects on the human organism. Nevertheless, the overall composition of the HBP remains not fully investigated. Thus, this research is focused on complementary proteomic and metabolomic characterization of biologically active compounds derived from HBP, regarding their toxicological and pharmacological properties. The objectives of the study will be achieved by the application of up to date mass spectrometry techniques. Due to increasing interest in using of HBP in medicine, this project will contribute to improving the safety of HBP‑derived dietary supplements and drugs.
Eliza Matuszewska; Paweł Dereziński; Agnieszka Klupczyńska; Agata Światły-Błaszkiewicz; Szymon Plewa; Jan Lubawy; Arkadiusz Urbański; Grzegorz Rosiński; Zenon Kokot; Jan Matysiak. Characterization of the selected honeybee products based on omics techniques. Journal of Medical Science 2019, 88, 129 -132.
AMA StyleEliza Matuszewska, Paweł Dereziński, Agnieszka Klupczyńska, Agata Światły-Błaszkiewicz, Szymon Plewa, Jan Lubawy, Arkadiusz Urbański, Grzegorz Rosiński, Zenon Kokot, Jan Matysiak. Characterization of the selected honeybee products based on omics techniques. Journal of Medical Science. 2019; 88 (2):129-132.
Chicago/Turabian StyleEliza Matuszewska; Paweł Dereziński; Agnieszka Klupczyńska; Agata Światły-Błaszkiewicz; Szymon Plewa; Jan Lubawy; Arkadiusz Urbański; Grzegorz Rosiński; Zenon Kokot; Jan Matysiak. 2019. "Characterization of the selected honeybee products based on omics techniques." Journal of Medical Science 88, no. 2: 129-132.
Despite of almost a hundred years of research on cancer metabolism, the biological background of cancerogenesis and cancer-related reprogramming of metabolism remains not fully understood. In order to comprehensively and effectively diagnose and treat the deadliest diseases, the mechanisms underlying these diseases have to be discovered urgently. Among the gynecological malignancies, ovarian cancer is the most common cause of death. The aim of the study was to search for potential cancer-related differences in concentrations of metabolites and interactions between them in serum of women with ovarian cancer and benign ovarian tumor in comparison with healthy controls using targeted metabolomics. These metabolites might serve as biomarkers in the future. We used wide spectrum targeted metabolomics to evaluate serum concentrations of metabolites related to ovarian cancer and compared them against benign ovarian tumors and healthy controls. The measurements were performed using high performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry technique in highly-selective multiple reaction monitoring mode. In this study we confirmed our previous findings about the role of histidine and citrulline in ovarian cancer as well as we indicated new lipid compounds (lysoPC a C16:1, PC aa C32:2, PC aa C34:4 and PC aa C 36:6) potentially involved in cancer metabolism. We indicated interesting interactions between metabolites for further in-depth research which could potentially serve as clinically useful biomarkers in future. Moreover, the presented work attempts to visualize a possible 3D-network of relationships between the molecules found to be related to ovarian malignancy.
Szymon Plewa; Agnieszka Horała; Paweł Dereziński; Ewa Nowak-Markwitz; Jan Matysiak; Zenon J. Kokot. Wide spectrum targeted metabolomics identifies potential ovarian cancer biomarkers. Life Sciences 2019, 222, 235 -244.
AMA StyleSzymon Plewa, Agnieszka Horała, Paweł Dereziński, Ewa Nowak-Markwitz, Jan Matysiak, Zenon J. Kokot. Wide spectrum targeted metabolomics identifies potential ovarian cancer biomarkers. Life Sciences. 2019; 222 ():235-244.
Chicago/Turabian StyleSzymon Plewa; Agnieszka Horała; Paweł Dereziński; Ewa Nowak-Markwitz; Jan Matysiak; Zenon J. Kokot. 2019. "Wide spectrum targeted metabolomics identifies potential ovarian cancer biomarkers." Life Sciences 222, no. : 235-244.
Introduction. Recent instrumentation and software advancement enabled to develop new, high‑throughput targeted metabolomics methods for in‑depth exploration of metabolome in a quantitative manner.Material and Methods. The presented targeted metabolomics approach allows to analyze both of serum and CSF in the same way, with identical sample preparation procedures. The analyses were carried out using high‑performance liquid chromatography system coupled to triple quadrupole tandem mass spectrometer with electrospray ion source (LC‑ESI‑QqQ‑MS/MS). Results. The applied targeted metabolomics approach enabled to determine a wide panel of metabolites from different chemical classes of compounds including: acylcarnitines, amino acids and biogenic amines, glycerophospholipids, sphingolipids and sum of hexoses. Finally, 148 metabolites in serum and 57 in cerebrospinal fluid were determined.Conclusions. Here we presented the results of successful implementation of the method of analysis of low‑molecular weight compounds in human serum and CSF using targeted metabolomics. The evaluation of selected groups of metabolites resulted in obtaining the mean concentrations of panel of metabolites in serum and CSF, which gives a valuable information about the metabolome of these matrices.
Szymon Plewa; Paweł Dereziński; Jolanta Florczak-Wyspiańska; Karolina Popławska-Domaszewicz; Wojciech Kozubski; Bartosz Sokół; Roman Jankowski; Jan Matysiak; Zenon J. Kokot. LC-MS/MS based targeted metabolomics method for analysis of serum and cerebrospinal fluid. Journal of Medical Science 2019, 88, 12 -20.
AMA StyleSzymon Plewa, Paweł Dereziński, Jolanta Florczak-Wyspiańska, Karolina Popławska-Domaszewicz, Wojciech Kozubski, Bartosz Sokół, Roman Jankowski, Jan Matysiak, Zenon J. Kokot. LC-MS/MS based targeted metabolomics method for analysis of serum and cerebrospinal fluid. Journal of Medical Science. 2019; 88 (1):12-20.
Chicago/Turabian StyleSzymon Plewa; Paweł Dereziński; Jolanta Florczak-Wyspiańska; Karolina Popławska-Domaszewicz; Wojciech Kozubski; Bartosz Sokół; Roman Jankowski; Jan Matysiak; Zenon J. Kokot. 2019. "LC-MS/MS based targeted metabolomics method for analysis of serum and cerebrospinal fluid." Journal of Medical Science 88, no. 1: 12-20.
In presented study the amino acid analysis was performed in serum derived from rheumatoid arthritis patients (RA) according to undertaken therapy and classification of physical disability. The results were compared with previously published data. The levels of 31 free amino acids were determined in 50 serum samples derived from RA subjects and 51 controls. The RA patients were divided into two groups according to the therapy (methotrexate/leflunomide, infliximab/adalimumab/etanercept/tocilizumab, prednisolone/NSAID) and classification of physical disability of the patients. Levels of amino acids were measured by LC-MS/MS. The obtained results were subjected to multivariate statistical tests. According to the therapy that was being used, threonine differentiated RA patients treated with methotrexate/leflunomide - infliximab/adalimumab/etanercept/tocilizumab (p = 0.00954) and infliximab/adalimumab/etanercept/tocilizumab - prednisolone/NSAID (p = 0.03109), while tryptophan differentiated RA patients treated with methotrexate/leflunomide - infliximab/adalimumab/etanercept/tocilizumab (p = 0.01723). In the functional classification, arginine differentiated RA samples between class III and IV (p = 0.02332), while glycine differentiated them between class I+II and III of the Steinbrocker functional classification (p = 0.03366). An analysis of the metabolome profile requires the use of validated bioanalytical methods that are strictly dedicated for this purpose. The obtained results are not accidental (p value less than 0.05), and all of the selected amino acids play an important role in inflammation and immune response. It is suggested that studied amino acids can be considered as a markers for diagnosis of RA and monitoring pharmacotherapy of the disease.
Bartosz Urbaniak; Szymon Plewa; Agnieszka Klupczynska; Dorota Sikorska; Włodzimierz Samborski; Zenon J. Kokot. Serum free amino acid levels in rheumatoid arthritis according to therapy and physical disability. Cytokine 2018, 113, 332 -339.
AMA StyleBartosz Urbaniak, Szymon Plewa, Agnieszka Klupczynska, Dorota Sikorska, Włodzimierz Samborski, Zenon J. Kokot. Serum free amino acid levels in rheumatoid arthritis according to therapy and physical disability. Cytokine. 2018; 113 ():332-339.
Chicago/Turabian StyleBartosz Urbaniak; Szymon Plewa; Agnieszka Klupczynska; Dorota Sikorska; Włodzimierz Samborski; Zenon J. Kokot. 2018. "Serum free amino acid levels in rheumatoid arthritis according to therapy and physical disability." Cytokine 113, no. : 332-339.
Ovarian cancer has emerged as one of the leading cause of gynecological malignancies. So far, the measurement of CA125 and HE4 concentrations in blood and transvaginal ultrasound examination are essential ovarian cancer diagnostic methods. However, their sensitivity and specificity are still not sufficient to detect disease at the early stage. Moreover, applied treatment may appear to be ineffective due to drug-resistance. Because of a high mortality rate of ovarian cancer, there is a pressing need to develop innovative strategies leading to a full understanding of complicated molecular pathways related to cancerogenesis. Recent studies have shown the great potential of clinical proteomics in the characterization of many diseases, including ovarian cancer. Therefore, in this review, we summarized achievements of proteomics in ovarian cancer management. Since the development of mass spectrometry has caused a breakthrough in systems biology, we decided to focus on studies based on this technique. According to PubMed engine, in the years 2008–2010 the number of studies concerning OC proteomics was increasing, and since 2010 it has reached a plateau. Proteomics as a rapidly evolving branch of science may be essential in novel biomarkers discovery, therapy decisions, progression predication, monitoring of drug response or resistance. Despite the fact that proteomics has many to offer, we also discussed some limitations occur in ovarian cancer studies. Main difficulties concern both complexity and heterogeneity of ovarian cancer and drawbacks of the mass spectrometry strategies. This review summarizes challenges, capabilities, and promises of the mass spectrometry-based proteomics techniques in ovarian cancer management.
Agata Swiatly; Szymon Plewa; Jan Matysiak; Zenon J. Kokot. Mass spectrometry-based proteomics techniques and their application in ovarian cancer research. Journal of Ovarian Research 2018, 11, 1 -13.
AMA StyleAgata Swiatly, Szymon Plewa, Jan Matysiak, Zenon J. Kokot. Mass spectrometry-based proteomics techniques and their application in ovarian cancer research. Journal of Ovarian Research. 2018; 11 (1):1-13.
Chicago/Turabian StyleAgata Swiatly; Szymon Plewa; Jan Matysiak; Zenon J. Kokot. 2018. "Mass spectrometry-based proteomics techniques and their application in ovarian cancer research." Journal of Ovarian Research 11, no. 1: 1-13.
Metabolomic studies constantly require high throughput screenings, and this drives development and optimization of methods that include more analytes in a single run, shorten the analysis time and simplify sample preparation. The aim of the study was to develop a new simple and fast liquid chromatography-tandem mass spectrometry-based methodology for quantitative analysis of a panel of ten organic acids in urine. The metabolites selected for the study include ten molecules potentially associated with cancer development. Chromatographic separation involved a Phenomenex Synergi Hydro-RP column under gradient conditions. Quantitation of the analytes was performed in multiple reaction monitoring mode under negative ionization. Validation parameters were satisfactory and in line with the international guidelines. The methodology enabled us to analyze urine samples collected from prostate cancer (PC) (n = 49) and benign prostate hyperplasia (BPH) (n = 49) patients. The obtained concentrations were normalized with urinary specific gravity (USG) prior to statistical analysis. Five analytes were quantified in all urine samples and we observed the following USG-normalized concentration ranges: citric acid (146.5 -6339.8), 3-hydroxyisobutyric acid (22.5-431.7), 2-ketoglutaric acid (4.4-334.4), lactic acid (10.1-786.3), succinic acid (4.1-500.5). 3-hydroxyisobutyric acid significantly decreased between two groups of prostate cancer patients: ≥7 Gleason patients and <7 Gleason patients. Quick sample preparation limited to “dilute and shoot” makes the developed methodology a great tool for future metabolomic studies, especially for detecting disturbances in energy metabolism (Krebs cycle) and amino acids metabolism. The research also broadens our knowledge on the alteration of selected organic acids in PC and BPH patients.
Agnieszka Klupczynska; Szymon Plewa; Natalia Sytek; Wojciech Sawicki; Paweł Dereziński; Jan Matysiak; Zenon J. Kokot. A study of low-molecular-weight organic acid urinary profiles in prostate cancer by a new liquid chromatography-tandem mass spectrometry method. Journal of Pharmaceutical and Biomedical Analysis 2018, 159, 229 -236.
AMA StyleAgnieszka Klupczynska, Szymon Plewa, Natalia Sytek, Wojciech Sawicki, Paweł Dereziński, Jan Matysiak, Zenon J. Kokot. A study of low-molecular-weight organic acid urinary profiles in prostate cancer by a new liquid chromatography-tandem mass spectrometry method. Journal of Pharmaceutical and Biomedical Analysis. 2018; 159 ():229-236.
Chicago/Turabian StyleAgnieszka Klupczynska; Szymon Plewa; Natalia Sytek; Wojciech Sawicki; Paweł Dereziński; Jan Matysiak; Zenon J. Kokot. 2018. "A study of low-molecular-weight organic acid urinary profiles in prostate cancer by a new liquid chromatography-tandem mass spectrometry method." Journal of Pharmaceutical and Biomedical Analysis 159, no. : 229-236.
Corrigendum: Amino Acids in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Haemorrhage: An Observational Study
Bartosz Sokół; Bartosz Urbaniak; Norbert Wąsik; Szymon Plewa; Agnieszka Klupczynska; Roman Jankowski; Barbara Więckowska; Robert Juszkat; Zenon Kokot. Corrigendum: Amino Acids in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Haemorrhage: An Observational Study. Frontiers in Neurology 2018, 9, 1 .
AMA StyleBartosz Sokół, Bartosz Urbaniak, Norbert Wąsik, Szymon Plewa, Agnieszka Klupczynska, Roman Jankowski, Barbara Więckowska, Robert Juszkat, Zenon Kokot. Corrigendum: Amino Acids in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Haemorrhage: An Observational Study. Frontiers in Neurology. 2018; 9 ():1.
Chicago/Turabian StyleBartosz Sokół; Bartosz Urbaniak; Norbert Wąsik; Szymon Plewa; Agnieszka Klupczynska; Roman Jankowski; Barbara Więckowska; Robert Juszkat; Zenon Kokot. 2018. "Corrigendum: Amino Acids in Cerebrospinal Fluid of Patients With Aneurysmal Subarachnoid Haemorrhage: An Observational Study." Frontiers in Neurology 9, no. : 1.
Agnieszka Karbownik; Edyta Szalek; Katarzyna Sobańska; Agnieszka Klupczynska; Szymon Plewa; Tomasz Grabowski; Anna Wolc; Marta Moch; Zenon J. Kokot; Edmund Grzeskowiak. A pharmacokinetic study on lapatinib in type 2 diabetic rats. Pharmacological Reports 2018, 70, 191 -195.
AMA StyleAgnieszka Karbownik, Edyta Szalek, Katarzyna Sobańska, Agnieszka Klupczynska, Szymon Plewa, Tomasz Grabowski, Anna Wolc, Marta Moch, Zenon J. Kokot, Edmund Grzeskowiak. A pharmacokinetic study on lapatinib in type 2 diabetic rats. Pharmacological Reports. 2018; 70 (2):191-195.
Chicago/Turabian StyleAgnieszka Karbownik; Edyta Szalek; Katarzyna Sobańska; Agnieszka Klupczynska; Szymon Plewa; Tomasz Grabowski; Anna Wolc; Marta Moch; Zenon J. Kokot; Edmund Grzeskowiak. 2018. "A pharmacokinetic study on lapatinib in type 2 diabetic rats." Pharmacological Reports 70, no. 2: 191-195.
Lapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer. Paracetamol is an analgesic commonly applied to patients with mild or moderate pain and fever. Cancer patients are polymedicated, which involves high risk of drug interactions during therapy. The aim of the study was to assess the interaction between lapatinib and paracetamol in rats. The rats were divided into three groups of eight animals in each. One group received lapatinib + paracetamol (IL + PA), another group received lapatinib (IIL), whereas the last group received paracetamol (IIIPA). A single dose of lapatinib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. Plasma concentrations of lapatinib, paracetamol and its metabolites – glucuronide and sulphate, were measured with the validated HPLC-MS/MS method and HPLC-UV method, respectively. The pharmacokinetic parameters of both drugs were calculated using non-compartmental methods. The co-administration of lapatinib and paracetamol increased the area under the plasma concentration-time curve (AUC) and the maximum concentration (Cmax) of lapatinib by 239.6% (p = 0.0030) and 184% (p = 0.0011), respectively. Lapatinib decreased the paracetamol AUC0-∞ by 48.8% and Cmax by 55.7%. In the IL + PA group the Cmax of paracetamol glucuronide was reduced, whereas the Cmax of paracetamol sulphate was higher than in the IIIPA group. Paracetamol significantly affected the enhanced plasma exposure of lapatinib. Additionally, lapatinib reduced the concentrations of paracetamol. The co-administration of lapatinib decreased the paracetamol glucuronidation but increased the sulphation. The findings of this study may be of clinical relevance to patients requiring analgesic therapy.
Agnieszka Karbownik; Edyta Szalek; Katarzyna Sobańska; Tomasz Grabowski; Agnieszka Klupczynska; Szymon Plewa; Anna Wolc; Magdalena Magiera; Joanna Porażka; Zenon Kokot; Edmund Grzeskowiak. The concomitant use of lapatinib and paracetamol - the risk of interaction. Investigational New Drugs 2018, 36, 819 -827.
AMA StyleAgnieszka Karbownik, Edyta Szalek, Katarzyna Sobańska, Tomasz Grabowski, Agnieszka Klupczynska, Szymon Plewa, Anna Wolc, Magdalena Magiera, Joanna Porażka, Zenon Kokot, Edmund Grzeskowiak. The concomitant use of lapatinib and paracetamol - the risk of interaction. Investigational New Drugs. 2018; 36 (5):819-827.
Chicago/Turabian StyleAgnieszka Karbownik; Edyta Szalek; Katarzyna Sobańska; Tomasz Grabowski; Agnieszka Klupczynska; Szymon Plewa; Anna Wolc; Magdalena Magiera; Joanna Porażka; Zenon Kokot; Edmund Grzeskowiak. 2018. "The concomitant use of lapatinib and paracetamol - the risk of interaction." Investigational New Drugs 36, no. 5: 819-827.
The aim of this study was to quantitate 42 serum-free amino acids, propose the biochemical explanation of their role in tumor development, and identify new ovarian cancer (OC) biomarkers for potential use in OC screening. The additional value of this work is the schematic presentation of the interrelationship between metabolites which were identified as significant for OC development and progression. The liquid chromatography-tandem mass spectrometry technique using highly-selective multiple reaction monitoring mode and labeled internal standards for each analyzed compound was applied. Performed statistical analyses showed that amino acids are potentially useful as OC biomarkers, especially as variables in multi-marker models. For the distinguishing metabolites the following metabolic pathways involved in cancer growth and development were proposed: histidine metabolism; tryptophan metabolism; arginine biosynthesis; arginine and proline metabolism; and alanine, aspartate and glutamine metabolism. The presented research identifies histidine and citrulline as potential new OC biomarkers. Furthermore, it provides evidence that amino acids are involved in metabolic pathways related to tumor growth and play an important role in cancerogenesis.
Szymon Plewa; Agnieszka Horała; Paweł Dereziński; Agnieszka Klupczynska; Ewa Nowak-Markwitz; Jan Matysiak; Zenon J. Kokot. Usefulness of Amino Acid Profiling in Ovarian Cancer Screening with Special Emphasis on Their Role in Cancerogenesis. International Journal of Molecular Sciences 2017, 18, 2727 .
AMA StyleSzymon Plewa, Agnieszka Horała, Paweł Dereziński, Agnieszka Klupczynska, Ewa Nowak-Markwitz, Jan Matysiak, Zenon J. Kokot. Usefulness of Amino Acid Profiling in Ovarian Cancer Screening with Special Emphasis on Their Role in Cancerogenesis. International Journal of Molecular Sciences. 2017; 18 (12):2727.
Chicago/Turabian StyleSzymon Plewa; Agnieszka Horała; Paweł Dereziński; Agnieszka Klupczynska; Ewa Nowak-Markwitz; Jan Matysiak; Zenon J. Kokot. 2017. "Usefulness of Amino Acid Profiling in Ovarian Cancer Screening with Special Emphasis on Their Role in Cancerogenesis." International Journal of Molecular Sciences 18, no. 12: 2727.
Background: The authors are aware of only one article investigating amino acid concentrations in cerebrospinal fluid (CSF) in patients with ruptured intracranial aneurysms, and this was published 31 years ago. Since then, both management of subarachnoid haemorrhage (SAH) and amino acid assay techniques have seen radical alterations, yet the pathophysiology of SAH remains unclear. Objective: To analyse the pattern of concentrations of amino acids and related compounds in patients with different outcomes following aneurysmal SAH. Methods: 49 CSF samples were collected from 23 patients on days 0-3, 5 and 10 post-SAH. Concentrations of 33 amino acids and related compounds were assayed by liquid chromatography tandem-mass spectrometry in patients with good (Glasgow Outcome Scale 1-3) and poor (Glasgow Outcome Scale 4-5) outcome. Results: Of the 33 compounds assayed, only hydroxyproline and 3-aminoisobutyric acid appeared not to increase significantly following SAH. In poor outcome patients we found significantly higher concentrations of aspartic acid (p=0.038), glutamic acid (p=0.038) and seven other compounds on day 0-3 post-SAH; glutamic acid (p=0.041) on day 5 post-SAH, and 2-aminoadipic acid (p=0.033) on day 10 post-SAH. The most significant correlation with Glasgow outcome scale at three months was found for aminoadipic acid on day 10 post-SAH (cc= -0.81). Conclusions: Aneurysmal rupture leads to a generalised increase of amino acids and related compounds in CSF. The patterns differ between good and poor outcome cases. Increased excitatory amino acids are strongly indicative of poor outcome.
Bartosz Sokół; Bartosz Urbaniak; Norbert Wąsik; Szymon Plewa; Agnieszka Klupczynska; Roman Jankowski; Barbara Więckowska; Robert Juszkat; Zenon Kokot. Amino Acids in Cerebrospinal Fluid of Patients with Aneurysmal Subarachnoid Haemorrhage: An Observational Study. Frontiers in Neurology 2017, 8, 438 -438.
AMA StyleBartosz Sokół, Bartosz Urbaniak, Norbert Wąsik, Szymon Plewa, Agnieszka Klupczynska, Roman Jankowski, Barbara Więckowska, Robert Juszkat, Zenon Kokot. Amino Acids in Cerebrospinal Fluid of Patients with Aneurysmal Subarachnoid Haemorrhage: An Observational Study. Frontiers in Neurology. 2017; 8 ():438-438.
Chicago/Turabian StyleBartosz Sokół; Bartosz Urbaniak; Norbert Wąsik; Szymon Plewa; Agnieszka Klupczynska; Roman Jankowski; Barbara Więckowska; Robert Juszkat; Zenon Kokot. 2017. "Amino Acids in Cerebrospinal Fluid of Patients with Aneurysmal Subarachnoid Haemorrhage: An Observational Study." Frontiers in Neurology 8, no. : 438-438.