Robert Kubina

Ganodermanontriol (GDNT), a lanostane‐type triterpenoid derived from Ganoderma lucidum , exhibits multiple pharmacological properties, with emerging evidence supporting its anticancer potential. Despite the long‐standing medicinal use of G. lucidum , the specific role and mechanisms of GDNT in oncology require further clarification. This review presents a comprehensive analysis of preclinical studies investigating the anticancer activity of GDNT in various cancer types, including nasopharyngeal, hepatocellular, gastric, colorectal, breast, prostate, and lung malignancies. Relevant experimental literature was identified and evaluated, with emphasis on in vitro and in vivo models exploring the molecular mechanisms of GDNT. Key pathways implicated in its activity include NF‐κB/MAPK, TLR4/MyD88, Wnt/β‐catenin, CES2/MPA metabolism, and androgen receptor signaling. Experimental findings demonstrate that GDNT induces apoptosis, arrests cell cycle progression, and inhibits tumor cell proliferation, migration, and invasion. It also modulates the tumor microenvironment through suppression of M2 macrophage polarization and pro‐tumor cytokine expression. Semi‐synthetic analogs of GDNT display improved cytotoxicity and selectivity, highlighting the relevance of structural optimization in enhancing bioactivity. Although clinical data on GDNT are currently lacking, studies involving G. lucidum extracts suggest potential benefits as supportive agents in oncologic care, particularly in immune modulation and enhancement of chemotherapeutic efficacy. Ongoing research into GDNT's pharmacological profile, including its derivatives, may support its development as a novel candidate in cancer therapeutics.

Cancers, including ovarian cancer, are a growing public health problem due to their high incidence and mortality rates. Ovarian cancer is a particularly challenging neoplasm to diagnose in its early stages due to the absence of specific symptoms and the paucity of effective diagnostic methods. The standard treatment regime for this condition includes surgical intervention, the administration of chemotherapy, and radiation therapy. Flavonoids, a prevalent class of phytonutrients, have been demonstrated to possess a plethora of biological properties, including antioxidant, anti-inflammatory, and anticancer properties. Quercetin, a widely recognised flavonol, has garnered significant attention due to its limited bioavailability, which has prompted the exploration of novel, more active derivatives. Research has demonstrated that structural modifications, incorporating the incorporation of groups comprising single, double or triple bonds, can substantially augment anticancer activity by modulating apoptosis, inhibiting angiogenesis and constraining cancer cell migration. In the course of the study, a series of new quercetin derivatives were synthesised, and their effects on ovarian cancer cells and normal cells were evaluated. Two compounds were selected from among those obtained, which showed particularly strong activity against the OVCAR-3 and SW626 cell lines. Furthermore, thermogravimetric analysis (TGA) was employed to ascertain the thermal stability and physicochemical properties of the compounds under investigation.

Head and neck squamous cell carcinoma (HNSCC) is a therapeutically challenging cancer what underscoring the need for new chemical agents that selectively induce programmed cell death. Fisetin, a naturally occurring flavonoid, exhibits promising anticancer activity but displays limited proapoptotic efficacy and selectivity. Here, we examined whether alkoxylated modification of fisetin enhances its ability to induce apoptosis in HNSCC cells. Fisetin derivatives bearing four-carbon substituents were synthesized and evaluated in multiple HNSCC cell lines. Two derivatives, MKT218 and MKT257, markedly reduced HNSCC cell viability at low micromolar concentrations with low toxicity towards normal human fibroblasts. Notably, the observed cytotoxicity was not associated with activation of a canonical DNA damage response, as neither γH2AX accumulation nor p53 activation was detected. Furthermore, PARP1 cleavage and live-cell imaging combined with annexin V/EthD-III staining revealed a significantly higher proportion of apoptotic cells. The effect was stronger following treatment with MKT218 and MKT257 compared with fisetin. Time-lapse microscopy further demonstrated that fisetin derivatives, particularly MKT218, promote mitosis-associated apoptosis, in contrast to the predominantly cytostatic effect of fisetin. Moreover, in silico docking suggested that MKT218 exerts its pro-apoptotic activity through a multi-target interaction profile involving key regulators of cell survival and apoptosis rather than a single dominant target. To sum up, our findings suggest that alkoxylated fisetin derivatives may be constituted as new non-genotoxic inducers of apoptosis in HNSCC cells.

Chrysin belongs to natural flavonoids characterized wide spectrum of biological activity. Its use in treatment is limited by low bioavailability and rapid metabolism. The structure-activity relationship shows that introduction of substituent at C7 position of flavone scaffold increase the activity and bioavailability. In this study, a series of quinoline-chrysin hybrids was obtained. The structure of compounds was determined using spectroscopic methods. The anticancer activity of compounds was tested against neck and head squamous cell carcinoma lines (HNSCC), while the antioxidant activity was determined using DPPH method. The biological effect depends on the type of quinoline moiety. For the most active compounds, IC₅₀ values as low as ~ 13.8 µM for anticancer activity and ~ 24.5 µM for antioxidant activity were observed. For the most active compounds, their effect on the expression levels of TP53, BAX, and BCL2 genes was examined.

Background: CRISPR/Cas genome editing is emerging as a powerful tool in oral and maxillofacial medicine, with potential applications in personalized therapies for conditions that currently lack durable treatments. Objectives: This scoping review aimed to map existing evidence on CRISPR-based applications in oral and maxillofacial fields, rather than to assess treatment effectiveness. Methods: A systematic search of PubMed, Scopus, Web of Science, and ClinicalTrials.gov (2012–2024) identified studies and registered trials involving CRISPR with oral health relevance. Eligible articles included peer-reviewed experimental reports and clinical trials. Results: From 1437 records, 121 studies met inclusion criteria: 106 preclinical reports and 15 clinical or translational studies. Investigated domains included oral cancer therapy, hereditary craniofacial syndromes, regenerative strategies, infectious disease models, and pathogen detection. Early clinical efforts focus mainly on CRISPR-edited T-cell immunotherapies in oncology. Major barriers include off-target effects, delivery challenges, regulatory complexity, and ethical concerns. Conclusions: CRISPR-based bioengineering shows strong promise for precision care in oral and maxillofacial medicine. However, current evidence remains largely preclinical and heterogeneous. No clinical recommendations can yet be made, and translation will depend on rigorous late-phase trials, ethical oversight, and health-economic evaluation.

NETs are network-like structures consisting mainly of DNA and various proteins released by neutrophils physiologically in response to pathogens. Moreover, according to recent reports, NETs also play an important role in carcinogenesis. They are involved in all stages of carcinogenesis, assist in the process of metastasis, and their presence has been linked to higher mortality and poorer prognosis in numerous cancer types. This review focuses on anti-cancer treatments related to disintegration of existing NETs, inhibition of their formation and regulation of their formation. Cases in which the presence of NETs was associated with anti-cancer activity and the association of NETs with complications co-occurring with cancer or related to cancer treatment was presented. This paper also presents mechanisms of NETs inhibition, predicting the efficacy or resistance of anti-cancer therapy associated with NETs.

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of tumors with a complex molecular profile. Despite therapeutic advances, patient prognosis remains poor, emphasizing the need for more effective treatment strategies. Traditional chemotherapy, with cisplatin and 5-fluorouracil (5-FU), remains the gold standard but is limited by toxicity and tumor resistance. Immunotherapy, particularly immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and its ligand (PD-L1), has improved overall survival, especially in patients with high PD-L1 expression. In parallel, targeted therapies such as poly (ADP-ribose) polymerase 1 (PARP1) inhibitors—which impair DNA repair and increase replication stress—have shown promising activity in HNSCC. Cyclin-dependent kinase (CDK) inhibitors are also under investigation due to their potential to correct dysregulated cell cycle control, a hallmark of HNSCC. This review aims to summarize current and emerging pharmacotherapies for HNSCC, focusing on chemotherapy, immunotherapy, and PARP and CDK inhibitors. It also discusses the evolving role of targeted therapies in improving clinical outcomes. Future research directions include combination therapies, nanotechnology-based delivery systems to enhance treatment specificity, and the development of diagnostic tools such as PARP1-targeted imaging to better guide personalized treatment approaches.

Neutrophil extracellular traps (NETs) are physiologically released in response to pathogens, serving as a defense mechanism. However, excessive NET production has been implicated in various pathological conditions, including diseases of the female reproductive system. Recent studies highlight the significant role of neutrophils and NETs in cancer pathogenesis. Overproduction of NETs creates sites for tumor cell adhesion, promoting tumor cell proliferation, immune escape, and tumor progression. NET formation is associated with many diseases, including cancers of the female reproductive organs. Detection of NETs can be used as a prognostic tool for patients with diseases characterized by higher rates of NETs formation, such as cancer. In order to use NETs in diagnosis, it is possible to determine them directly or to determine NET components: extracellular DNA, citrullinated histones, NE or MPO. This review explores the role of neutrophils and NETs in the pathogenesis, diagnosis and treatment of breast, ovarian, cervical and endometrial cancer, premature lapse of ovarian function, cervicitis, endometriosis, pregnancy and pregnancy-related diseases.

Hexahydrocurcumin (HHC), the primary metabolite of curcumin, shows promising therapeutic potential due to its antioxidant and anti-inflammatory properties. The retinal pigment epithelium (RPE) plays a crucial role in maintaining retinal homeostasis; however, its dysfunction—linked to oxidative stress and chronic inflammation—contributes to the progression of degenerative diseases such as age-related macular degeneration (AMD). This review highlights the therapeutic potential of HHC in protecting and regenerating RPE cells. It explores the effects of oxidative stress on the RPE, the mechanisms underlying its damage, and the involvement of reactive oxygen species (ROS) and inflammatory mediators. HHC has demonstrated the ability to modulate these pathways by activating nuclear factor erythroid 2-related factor 2 (NRF2), enhancing antioxidant defenses, and inhibiting pro-inflammatory cytokine production. Preclinical studies suggest that HHC mitigates vascular remodeling and endothelial dysfunction by reducing the expression of transforming growth factor β (TGF-β1) and matrix metalloproteinase-9 (MMP-9). Moreover, HHC improves nitric oxide bioavailability and promotes nitric oxide synthase expression, thereby counteracting oxidative stress-induced vascular damage. Emerging evidence indicates that HHC may be a promising candidate for the treatment of retinal degenerative diseases, particularly those associated with oxidative stress and inflammation. However, further studies, including clinical trials, are essential to confirm its efficacy and elucidate the precise mechanisms underlying HHC’s protective effects on RPE cells.

This paper presents a multifaceted assessment of inhibitors of anti-apoptotic proteins (IAPs) in the context of head and neck squamous cell carcinoma (HNSCC). The article discusses the results of in vitro, in vivo, and clinical studies, highlighting the significance of IAPs in the resistance of cancer cells to apoptosis, which is a key factor hindering effective treatment. The main apoptosis pathways, including the intrinsic and extrinsic pathways, and the role of IAPs in their regulation, are presented. The study’s findings suggest that targeting IAPs with novel therapies may offer clinical benefits in the treatment of advanced HNSCC, especially in cases resistant to conventional treatment methods. These conclusions underscore the need for further research to develop more effective and safer therapeutic strategies.