Pawel Kozyra

Mr. Pawel Kozyra


Research Focus & Metrics

Academic Career Length

8Years (2019-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

View All Publications
24 September 2022 in Cancers
Verified
Journal Article
Open access
PDF file
Jacek BajJacek Baj
Jacek Baj
JDJames Curtis Dring
James Curtis Dring
MCMarcin Czeczelewski
Marcin Czeczelewski
PKPawel Kozyra
Pawel Kozyra
AFAlicja Forma
Alicja Forma
GTGrzegorz Teresinski
Grzegorz Teresinski
Micro- and nanoplatics have been already reported to be potential carcinogenic/mutagenic substances that might cause DNA damage, leading to carcinogenesis. Thus, the effects of micro- and nanoplastics exposure on human health are currently being investigated extensively to establish clear relationships between those substances and health consequences. So far, it has been observed that there exists a definite correlation between exposure to micro- and nanoplastic particles and the onset of several cancers. Therefore, we have conducted research using PubMed, Web of Science, and Scopus databases, searching for all the research papers devoted to cancers that could be potentially related to the subject of exposure to nano- and microplastics. Ultimately, in this paper, we have discussed several cancers, including hepatocellular carcinoma, pancreatic cancer, pancreatic ductal adenocarcinoma, biliary tract cancer, and some endocrine-related cancers.

Verified
Journal Article
Open access
PDF file
JKJoanna Kozak
Joanna Kozak
AFAlicja Forma
Alicja Forma
MCMarcin Czeczelewski
Marcin Czeczelewski
PKPawel Kozyra
Pawel Kozyra
RSRyszard Sitarz
Ryszard Sitarz
Jacek BajJacek Baj
Jacek Baj
Epithelial-mesenchymal transition (EMT) constitutes one of the hallmarks of carcinogenesis consisting in the re-differentiation of the epithelial cells into mesenchymal ones changing the cellular phenotype into a malignant one. EMT has been shown to play a role in the malignant transformation and while occurring in the tumor microenvironment, it significantly affects the aggressiveness of gastric cancer, among others. Importantly, after EMT occurs, gastric cancer patients are more susceptible to the induction of resistance to various therapeutic agents, worsening the clinical outcome of patients. Therefore, there is an urgent need to search for the newest pharmacological agents targeting EMT to prevent further progression of gastric carcinogenesis and potential metastases. Therapies targeted at EMT might be combined with other currently available treatment modalities, which seems to be an effective strategy to treat gastric cancer patients. In this review, we have summarized recent advances in gastric cancer treatment in terms of targeting EMT specifically, such as the administration of polyphenols, resveratrol, tangeretin, luteolin, genistein, proton pump inhibitors, terpenes, other plant extracts, or inorganic compounds.

18 January 2022 in Biomolecules
Verified
Journal Article
Open access
PDF file
PKPawel Kozyra
Pawel Kozyra
AKAgnieszka Korga-Plewko
Agnieszka Korga-Plewko
ZKZbigniew Karczmarzyk
Zbigniew Karczmarzyk
AHAnna M. Hawrył
Anna M. Hawrył
WWWaldemar Wysocki
Waldemar Wysocki
MPMonika Pitucha
Monika Pitucha
In this paper, thiosemicarbazide derivatives were synthesized as potential anticancer agents. X-ray investigations for 1-(2,4-dichlorophenoxy)acetyl-4-(2-fluorophenyl) thiosemicarbazide, 1-(2,4-dichlorophenoxy)acetyl-4-(4-metylothiophenyl)thiosemicarbazide and 1-(2,4-di chlorophenoxy)acetyl-4-(4-iodophenyl)thiosemicarbazide were carried out in order to confirm the synthesis pathways, identify their tautomeric forms, analyze the conformational preferences of molecules, and identify intra- and intermolecular interactions in the crystalline state. TLC and RP-HPLC analyses were used to determine lipophilicity. The lipophilicity analysis revealed that the 4-substituted halogen derivatives of thiosemicarbazides showed greater lipophilicity compared with 2-substituted derivatives. The optimal range of lipophilicity for biologically active compounds logkw is between 4.14 and 4.78. However, as the analysis showed, it is not a decisive parameter. The cytotoxicity of the new compounds was evaluated against both the G-361 and BJ cell lines. Cytotoxicity analyses and cell-cycle and cell apoptosis assays were performed. The MTT test demonstrated that three compounds were cytotoxic to melanoma cells and not toxic to normal fibroblasts in the concentration range used. The cell cycle analysis showed that the compounds had no significant effect on the cell cycle inhibition. An extensive gene expression analysis additionally revealed that all compounds tested downregulated the expression of dihydroorotate dehydrogenase (DHODH). DHODH is a mitochondrial enzyme involved in the de novo synthesis of pyrimidines. Due to the rapid rate of cancer cell proliferation and the increased demand for nucleotide synthesis, it has become a potential therapeutic target.

Verified
Journal Article
Open access
PDF file
PKPawel Kozyra
Pawel Kozyra
DKDanuta Krasowska
Danuta Krasowska
MPMonika Pitucha
Monika Pitucha
Malignant melanoma (MM) is the most lethal skin cancer. Despite a 4% reduction in mortality over the past few years, an increasing number of new diagnosed cases appear each year. Long-term therapy and the development of resistance to the drugs used drive the search for more and more new agents with anti-melanoma activity. This review focuses on the most recent synthesized anti-melanoma agents from 2020–2022. For selected agents, apart from the analysis of biological activity, the structure–activity relationship (SAR) is also discussed. To the best of our knowledge, the following literature review delivers the latest achievements in the field of new anti-melanoma agents.

13 February 2020 in Biomolecules
Verified
Journal Article
Open access
PDF file
MPMonika Pitucha
Monika Pitucha
AKAgnieszka Korga-Plewko
Agnieszka Korga-Plewko
PKPawel Kozyra
Pawel Kozyra
MIMagdalena Iwan
Magdalena Iwan
Agnieszka KaczorAgnieszka Kaczor
Agnieszka Kaczor
Thiosemicarbazide is a useful structural moiety that has the biological potential. Optimization of this structure can result in groundbreaking discovery of a new class of therapeutic agents. In the light of this, 1-(2,4-dichlorophenoxy)acetyl-4-(1-naphthyl)thiosemicarbazide (1) and 1,4-bis[(2,4-dichlorophenoxy)acetylthiosemicarbazide]phenyl (2) were synthesized and characterized by spectroscopic method. Cytotoxicity of obtained compounds was evaluated on MKN74 gastric cancer cell line and human skin fibroblast BJ based on methylthiazolyldiphenyl-tetrazolium bromide (MTT) test. The apoptosis/necrosis and cell cycle analysis were conducted using image cytometry. Additionally, in DNA of treated cells, abasic sites (AP) and double strands breaks (DSB) presence were measured. Intercalating properties of active compounds were evaluated using the UV–spectroscopic method. Among newly synthesized derivatives, compound 2 showed toxic effects on gastric cancer cells with simultaneous lack of toxicity to normal fibroblasts. Cell cycle analysis revealed that both compounds influence cell division mainly at the stage of replication. Simultaneously with DNA synthesis disorders, DNA damages like AP-sites and DSBs were observed. Spectroscopic studies revealed possible DNA intercalating properties of tested compounds. Obtained results indicate that the newly synthesized thiosemicarbazide derivatives are a promising group of compounds with potential anticancer activity resulted from interactions with DNA and cell cycle interrupt.

Verified
Journal Article
Open access
PDF file
PKPawel Kozyra
Pawel Kozyra
MPMonika Pitucha
Monika Pitucha
The terminal phenoxy group is a moiety of many drugs in use today. Numerous literature reports indicated its crucial importance for biological activity; thus, it is a privileged scaffold in medicinal chemistry. This review focuses on the latest achievements in the field of novel potential agents bearing a terminal phenoxy group in 2013–2022. The article provided information on neurological, anticancer, potential lymphoma agent, anti-HIV, antimicrobial, antiparasitic, analgesic, anti-diabetic as well as larvicidal, cholesterol esterase inhibitors, and antithrombotic or agonistic activities towards the adrenergic receptor. Additionally, for selected agents, the Structure–Activity–Relationship (SAR) is also discussed. Thus, this study may help the readers to better understand the nature of the phenoxy group, which will translate into rational drug design and the development of a more efficient drug. To the best of our knowledge, this is the first review devoted to an in-depth analysis of the various activities of compounds bearing terminal phenoxy moiety.