Scientific publications

Scientific article / Vetkompleksowo

Lymphoma in dogs remains a significant clinical challenge, because standard multi-agent chemotherapy provides a median survival of only 12 months. For this reason radiotherapy is gaining importance as an effective complementary method, exploiting the high radiosensitivity of neoplastic lymphocytes, particularly in the B-cell variant. Half-body irradiation (HBI), applied sequentially in combination with chemotherapy, is well tolerated and extends the median survival to more than 700 days. More aggressive total body irradiation (TBI), which forms part of the preparation for stem cell transplantation, makes it possible to achieve a cure rate of around 89% and a median survival exceeding 1,100 days, although it involves high costs and requires specialist care. The key to the success of both of these advanced protocols is achieving complete clinical remission with chemotherapy before radiotherapy begins.

Conference lecture

Lecture at the 14th Radiology and Surgery Conference, 16 March 2025, Kraków
"Wykorzystanie radioterapii w leczeniu nowotworów mózgu u psów" [The use of radiotherapy in the treatment of brain tumours in dogs]

Lecture abstract:
As dogs and cats live longer, brain tumours are becoming an increasingly frequently diagnosed problem in veterinary medicine. The treatment of central nervous system tumours includes palliative therapy, surgery and chemotherapy, among others; these methods often give unsatisfactory results because of complications, invasive growth of the lesions or drug resistance. In many cases – especially for glioma, meningioma and choroid plexus carcinoma – radiotherapy remains the treatment of choice. The use of ionising radiation, both as monotherapy and in combined regimens, significantly extends the median survival time of patients and improves their clinical condition with a relatively low rate of complications.

Biomedicines (PubMed: 39457553)

The article addresses overcoming the pharmacokinetic limitations of 2-deoxy-D-glucose (2-DG) by using its fluorinated analogues to block glycolysis, which is crucial for glioblastoma cells. The fluorinated derivatives turn out to have the strongest cytotoxic effect under hypoxic conditions, typical of the glioblastoma microenvironment. Enzymatic and spectroscopic analyses confirmed that the studied molecules inhibit hexokinase II much more effectively than standard 2-DG. Modification at the C-2 position increases the stability and uptake of the drug, raising hopes for more effective metabolic therapies.

Biomedicines (PubMed: 36359318)

WP1234 is a new derivative of 2-deoxy-D-glucose (2-DG) with improved pharmacokinetic properties, designed to fight glioblastoma multiforme (GBM). The compound has a bifunctional mechanism of action, releasing both 2-DG and 2-ethylbutyric acid inside cells. Studies showed that the released 2-DG effectively inhibits glycolysis and ATP synthesis, while 2-ethylbutyric acid acts as a histone deacetylase (HDAC) inhibitor. As a result, WP1234 significantly reduces the viability of cancer cells and induces their apoptosis in a dose- and time-dependent manner. The results indicate a high anticancer potential of this molecule, although its safety and efficacy require further studies in animal models.

Journal of Applied Genetics (PubMed: 34967917)

The article assesses the effect of long-term occupational exposure to toxic ammunition-related chemicals on genomic instability in professional soldiers. Attention was paid mainly to the risk of predisposition to lung cancer in personnel routinely testing explosives. To detect new somatic mutations, the innate DNA profile from swabs was compared with cell-free circulating DNA (ccfDNA) obtained by liquid biopsy. The analysis revealed new single nucleotide polymorphisms (SNPs) in genes associated with lung carcinogenesis in people exposed to chemicals over a long period. The results indicate that advanced molecular techniques can serve as an effective tool for early monitoring of the risk of developing lung cancer as a consequence of exposure to biological factors related to the work performed.

Biomedicines (PubMed: 34944565)

The article investigates a new strategy for treating glioblastoma multiforme, which, as an aggressive brain tumour, is largely dependent on aerobic glycolysis. To overcome the pharmacokinetic limitations of classic 2-deoxy-D-glucose (2-DG) as monotherapy, its modern analogues with better bioavailability were used, including the WP1122 molecule. The studies tested combination therapy, combining these glycolysis inhibitors with histone deacetylase (HDAC) inhibitors – sodium butyrate and sodium valproate. Experiments in the U-87 and U-251 cell models demonstrated that the simultaneous use of both groups of compounds produces a strong, synergistic cytotoxic effect against glioblastoma cells. The results indicate that simultaneously blocking energy metabolism and modulating epigenetic processes is a promising direction in developing new therapeutic options for glioblastoma multiforme.

Int J Mol Sci (PubMed: 33158194)

Muscle cachexia, i.e. cancer-induced muscle wasting, is currently one of the most serious and still unsolved challenges of modern medicine. However, identifying the molecular basis of muscle mass loss in cancer has opened promising possibilities for discovering new therapeutic targets and developing effective drugs. In this review article I analyse the JAK2/STAT3 signalling pathway in detail, defining the role of the STAT3 protein in the formation and growth of tumours. I also point to the key involvement of the same transcription factor in the mechanisms leading to the degradation and wasting of skeletal muscle. The paper highlights the therapeutic potential of an innovative treatment with a single agent inhibiting STAT3 activity, which would make it possible to block tumour development and prevent muscle cachexia at the same time.

Int J Mol Sci (PubMed: 31905745)

This review article discusses the use of 2-deoxy-D-glucose (2-DG) and its analogues as compounds with both diagnostic and therapeutic potential in oncology. The compound acts as a D-glucose mimetic and disrupts its metabolism, demonstrating that cutting cells off from nutrients and energy effectively inhibits tumour growth and survival. Intracellular accumulation of 2-deoxy-D-glucose-6-phosphate (2-DG6P) blocks the action of hexokinase and glucose-6-phosphate isomerase, which halts glycolysis and leads to cell death. Beyond inhibiting glycolysis, 2-DG also affects other molecular processes in cells. The paper analyses attempts to improve the pharmacological properties of 2-DG, its use as an adjuvant supporting other chemotherapeutic agents, and new analogues that represent promising anticancer drugs.

Journal of Clinical Medicine (PubMed: 31100888)

This paper analyses the molecular mechanisms of the protective action of geranylgeraniol (GGOH) on C2C12 skeletal muscle cells damaged as a result of myopathy induced by statins – atorvastatin (ATR) and simvastatin (SIM). I showed that although autophagy plays an important role in the differentiation of muscle cells itself, it does not take part in the cytoprotective action of GGOH, which effectively reverses the decrease in cell viability caused by both statins. My experiments also revealed that the mitochondria of the studied cells are insensitive to simvastatin, whereas atorvastatin strongly inhibits mitochondrial respiration, which can be restored to normal by GGOH. Apoptosis partly contributes to the reduced viability of myotubes, but inhibiting caspases partly reverses statin cytotoxicity through a caspase-3-independent route. The results indicate that GGOH prevents statin myopathy probably by inactivating the calpain system, which is confirmed by the fact that a calpain inhibitor (ALLM) effectively restored cell viability reduced by the studied statins.

Int J Mol Sci (PMC: 6212855 / PMID: 30241315)

This review article discusses the multiple functions of the Rap1 protein (a member of the Ras family of small GTPases) in various cell types, in both physiological and pathological states. The protein occurs in two isoforms (Rap1A and Rap1B) and acts as a molecular switch whose activity is stimulated by post-translational modifications (isoprenylation) and guanine nucleotide exchange factors (GEFs), and inhibited by GTPase-activating proteins (GAPs). Rap1 is activated in a variety of signalling pathways with the involvement of second messengers such as cAMP, calcium ions and diacylglycerol (DAG), in response to stimulation of various membrane receptors. It plays a key role in regulating cellular processes, including signal transduction, cytoskeletal remodelling necessary for cell division, cell–cell adhesion, and cell motility and fusion. In this paper I present numerous examples of the influence of Rap1 on the function of cells and organs – above all in cancer processes – pointing to potential molecular manipulation of this protein as a promising direction in the therapy of many cancers.

Oxid Med Cell Longev (PMC: 5987243 / PMID: 29951166)

The article analyses the mechanisms of myotoxicity induced by statins (atorvastatin and simvastatin) and methyl-beta-cyclodextrin (MβCD) in a model of mouse C2C12 muscle cells. I showed that the negative effect of statins on the survival of proliferating myoblasts does not result directly from lowering cholesterol levels, but from inhibition of the synthesis of intermediate metabolites of the mevalonate pathway. Administration of geranylgeraniol (GGOH) completely reverses the cytotoxic effect of statins in myoblasts, whereas water-soluble cholesterol (Chol-PEG) protects myocytes only against damage caused by MβCD. The protective effect of GGOH is associated with restoration of RAP1 protein prenylation, increased phosphorylation of the AKT1 and GSK-3β kinases, and increased levels of autophagy markers. These results indicate for the first time a direct link between GGOH and cholesterol supplementation and the activation of cytoprotective autophagy that rescues muscle cells from damage.

PLoS One (PubMed: 26466121)

This is my first scientific paper, which was written while I was still a student. The study aimed to determine how different types of musculoskeletal injuries affect the blood concentration of serum amyloid A (SAA) in racehorses. Together with my team, I analysed blood samples collected from 28 horses diagnosed after a race with bone fractures, dorsal metacarpal disease, joint injuries, or muscle and tendon damage, and from 28 healthy animals forming the control group. Measurements made by ELISA within the first four days after the injury showed a significantly higher mean SAA concentration only in horses with muscle and tendon injuries. In the other groups studied, which included bone and joint injuries, the level of this protein did not differ significantly from values observed in healthy horses. Overload injuries of muscles and tendons cause a moderate acute-phase response visible as a rise in SAA, whereas bone injuries related to mechanical stress do not cause a similar systemic response.