Head and neck squamous cell carcinoma (HNSCC) remains a major health burden, with abnormal activation of phosphatidylinositol 3-kinase alpha (PI3Kα) strongly implicated in its pathogenesis. Targeting PI3Kα represents a promising therapeutic strategy. In this study, we employed structure-based virtual screening to identify natural small-molecule inhibitors of PI3Kα. A total of 12,800 molecules were screened, and five compounds were selected for further evaluation based on binding affinity and interaction patterns. Pharmacokinetic properties were assessed using ADMET predictions, and molecular dynamics (MD) simulations were conducted to validate the binding stability. Among the candidates, Apigetrin demonstrated favorable ADMET properties, a high safety profile, and stable binding within the ATP-binding pocket of PI3Kα. These findings suggest that Apigetrin is a promising natural PI3Kα inhibitor with potential therapeutic relevance for HNSCC.

In the clinical setting, the efficacy of single-agent immune checkpoint inhibitors (ICIs) in triple-negative breast cancer (TNBC) remains suboptimal. Therefore, there is a pressing need to develop predictive biomarkers to identify non-responders. Considering that cancer-associated fibroblasts (CAFs) represent an integral component of the tumor microenvironment that affects the stiffness of solid tumors on shear-wave elastography (SWE) imaging, wound healing CAFs (WH CAFs) were identified in highly heterogeneous TNBC. This subtype highly expressed vitronectin (VTN) and constituted the majority of CAFs. Moreover, WH CAFs were negatively correlated with CD8+ T cell infiltration levels and influenced tumor proliferation in the Eo771 mouse model. Furthermore, multi-omics analysis validated its role in immunosuppression. In order to non-invasively classify patients as responders or non-responders to ICI monotherapy, a deep learning model was constructed to classify the level of WH CAFs based on SWE imaging. As anticipated, this model effectively distinguished the level of WH CAFs in tumors. Based on the classification of the level of WH CAFs, while tumors with a high level of WH CAFs were found to exhibit a poor response to anti programmed cell death protein 1 (PD-1) monotherapy, they were responsive to the combination of anti-PD-1 and erdafitinib, a selective fibroblast growth factor receptor (FGFR) inhibitor. Overall, these findings establish a reference for a novel non-invasive method for predicting ICI efficacy to guide the selection of TNBC patients for precision treatment in clinical settings.

Globally, lung cancer is the primary cause of deaths associated with cancer; however, current therapies are costly and toxic, highlighting the need for novel treatments. Peiminine (Verticinone), a key bioactive compound derived from Fritillaria ussuriensis Maxim., has demonstrated diverse biological activities. However, the precise pharmacological mechanisms underlying its anti-lung cancer effects remain unclear. The objective of this study was to quantify the content of peiminine in Fritillaria ussuriensis Maxim. from different geographical regions using UHPLC-MS/MS and to elucidate the anti-lung cancer mechanisms of peiminine through network pharmacology, bioinformatics, and in vitro experiments. The content of peiminine in Fritillaria ussuriensis Maxim. from various regions was determined using UHPLC-MS/MS. Potential target genes associated with peiminine and lung cancer were systematically screened from multiple databases. To identify core genes, we set up a PPI (protein-protein interaction) network, followed by in-depth analyses of their corresponding target proteins. Survival analysis, molecular docking, and dynamics simulations were used to explore potential anti-cancer mechanisms. In vitro experiments on human H1299 NSCLC cells assessed peiminine's anti-tumor activity and measured key gene transcription levels. UHPLC-MS/MS analysis revealed that Fritillaria ussuriensis Maxim. from Mudanjiang (Heilongjiang Province) exhibited the highest peiminine content. Network pharmacological analysis identified PIK3CG, SRC, JAK3, AKT2, and PRKCA as key potential targets of peiminine in lung cancer treatment. Molecular docking results demonstrated strong binding affinities between peiminine and PIK3CG, SRC, and JAK3; these results were further confirmed using molecular dynamics simulations. Survival analysis indicated that a high AKT2 and PRKCA expression correlated with bad prognosis in lung cancer patients. In vitro, peiminine inhibited H1299 cell viability and regulated genes involved in the PI3K-Akt pathway (PI3K, AKT, and PTEN) and apoptosis (Bcl-2, Bax), suggesting that it may induce its effects via PI3K-Akt pathway inhibition. Peiminine from Fritillaria ussuriensis Maxim. exhibits significant anti-lung cancer potential by targeting key genes such as PIK3CG, SRC, and JAK3, as well as by modulating the PI3K-Akt signaling pathway and apoptosis-related genes. These results lay a foundation for further investigations into peiminine as a potentially effective therapeutic option for treating lung cancer. Additionally, the identified targets (PIK3CG, SRC, JAK3, AKT2, and PRKCA) may function as possible biomarkers for predicting lung cancer prognosis and guiding personalized therapy.

A series of 3-azabicyclo[3.1.0]hexanes and cyclopropa[a]pyrrolizidines spiro-fused to acenaphthylene-1(2H)-one and aceanthrylene-1(2H)-one frameworks have been studied for their in vitro antiproliferative activity against human erythroleukemia (K562), cervical carcinoma (HeLa), melanoma (Sk-mel-2), osteosarcoma (U2OS), as well as murine melanoma (B16) cell lines. Using confocal microscopy, it was found that cultivation with the tested spiro-fused compounds led to the disappearance of stress fibers (granular actin was distributed diffusely in the cytoplasm in up to 56% of treated cells) and decrease in filopodia-like deformations (up to 69% after cultivation), which indirectly suggests a decrease in cell motility. The human melanoma cell line scratch test showed that these cells lose their ability to move after cultivation with the tested spiro-fused compounds and do not fill the scratched strip. This was also supported by docking simulations with actin-related targets (PDB ID: 8DNH, 2Q1N). Using flow cytometry, the impact on the mitochondrial membrane potential showed that the tested compounds led to a significant increase in the number of cells with decreased mitochondrial membrane potential from 10% for the control up to 55-80% for the cyclopropa[a]pyrrolizidine adducts. The obtained results support the antitumor effect of the tested spiro-compounds and encourage the extension of the study in order to improve their anticancer activity as well as reduce their toxicological risks.

Hepatocellular carcinoma (HCC) is a lethal malignancy associated with drug resistance, resulting in a poor prognosis. High mobility group box 1 (HMGB1) is a chromatin-binding protein that regulates HCC progression. The overexpression of HMGB1 has been found to promote tumorigenesis and drug resistance. In this study, we aimed to investigate the role of HMGB1 expression in tumorigenesis and metastasis and its impact on sorafenib and oxaliplatin resistance. Tissue samples from patients with HCC (n = 48) were subjected to immunohistochemistry. The expression of HMGB1 was correlated with clinical pathology parameters. Moreover, the HCC cell line HuH-7 was used to study the regulatory effect of HMGB1 on cell proliferation, cell adhesion, migration, and invasion by using the siRNA (small interfering RNA) silencing method. Furthermore, drug challenges were performed to determine the effect of HMGB1 on the sensitivity to chemotherapeutic drugs (sorafenib and oxaliplatin). HMGB1 was significantly overexpressed in tumor tissues, highlighted by the expression increment in patients with M1 advanced metastasis tumors with immunoreactivity scores 2.61 and 6.50 for adjacent and tumor tissues, respectively (p-values = 0.0035). The involved mechanisms were then described through the suppression of HCC cell adhesion, migration, and invasion by HMGB1 silencing. Notably, the inhibition of HMGB1 expression promoted sorafenib/oxaliplatin sensitivity in the HCC cell line by increasing the cell toxicity by about 13-18%. Our study demonstrated that HMGB1 shows potential as a promising biomarker and a target for HCC treatment that is involved in tumorigenesis, metastasis, and chemo-drug resistance.

The peptidergic systems are involved in neuroblastoma. Peptides (angiotensin II, neuropeptide Y, neurotensin, substance P) act as oncogenic agents in neuroblastoma, whereas others (adrenomedullin, corticotropin-releasing factor, urocortin, orexin) exert anticancer effects against neuroblastoma. This plethora of peptidergic systems show the functional complexity of the mechanisms regulated by peptides in neuroblastoma. Peptide receptor antagonists act as antineuroblastoma agents since these compounds counteracted neuroblastoma cell growth and migration and the angiogenesis promoted by oncogenic peptides. Other therapeutic approaches (signaling pathway inhibitors, focal adhesion kinase inhibitors, peptide receptor knockdown, acetic acid analogs) that also counteract the beneficial effects mediated by the oncogenic peptides in neuroblastoma are discussed, and future research lines to be developed in neuroblastoma (interactions between oncogenic and anticancer peptides, combination therapy using peptide receptor antagonists and chemotherapy/radiotherapy) are also suggested. Although the data regarding the involvement of the peptidergic systems in neuroblastoma are, in many cases, fragmentary or very scarce for a particular peptidergic system, taken together, they are quite promising with respect to potentiating and developing this research line with the aim of developing new therapeutic strategies to treat neuroblastoma in the future. Peptidergic systems are potential and promising targets for the diagnosis and treatment of neuroblastoma.

Plant extracts contain many small molecules that are less investigated. The present paper aims to study in silico physical-chemical, pharmacokinetic, medicinal chemistry and lead/drug-likeness properties and the ability to interfere with the activity of P-glycoprotein (P-gp) transporter and cytochrome P450 (CYP) oxidase system in humans of phloridzin, phloretin, 4-methylchalcone metabolic series alongside the top three compounds found in the ethanolic extract from strawberries (S), namely 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 2-pyrrolidinone 5-(cyclohexylmethyl) and hexadecanoic acid. The phloridzin derivatives also were studied for their inhibitory potential upon Bcl-2, TNKS1 and COX-2 molecular targets. In vitro, Caco-2 studies analyzed the cytoprotective and anti-proliferative activity of S and the three phloridzin derivatives (pure compounds) in comparison with their combination 1:1 (GAE/pure compound, w/w), in the range 1 to 50 µg active compounds per test sample. Altogether, it was concluded that phloretin (Phl) can be used alone or in combination with S to support intestinal cell health in humans. Phloridzin (Phd) and phloridzin combined with S were proven ineffective. 4-methylchalcone (4-MeCh) combined with S indicated no advantages, while the pure compound exhibited augmented inhibitory effects, becoming a candidate for combinations with anticancer drugs. Overall, in silico studies revealed possible limitations in the practical use of phloridzin derivatives due to their potential to interfere with the activity of several major CYP enzymes.

Intensive cancer treatment with nanoplatform is widely exploited in the clinic, the emerging nanomedicine offers an unparalleled opportunity for encapsulating potential antitumor drugs in a nano-carrier. Apoptin (AP), a coding protein of VP3 gene, stem from the chicken anemia virus (CAV), can be activated in malignant cells selectively and prevents the dividing cancer cells from repairing their DNA lesions, thereby forcing them to undergo apoptosis. Herein, a three-step intelligent biodegradable drug delivery nanoplatform was designed.

The primary aim of this article is to present cystoid macular oedema as one of the side effects of Paclitaxel (Taxol) chemotherapy. Paclitaxel is used as a treatment option in patients with different types of solid carcinomas. The potential loss of vision, already altered by the disease, further compromises their quality of life, a contributing factor to overall psychological and mental decline.

The objective of anti-VEGF (Vascular Endothelial Growth Factor) injections in the treatment of central serous chorioretinopathy (CSCR) is to help reduce fluid accumulation beneath the retina, promote resolution of retinal edema, and potentially prevent complications like permanent vision loss.The goal is to stabilize or improve vision by improving visual outcomes by reducing fluid and promoting retina reattachment.

Angiogenesis plays a critical role in the progression of gastrointestinal (GI) tumors, making it an important therapeutic target. This review explores recent advancements in targeting angiogenesis for GI tumor therapy, highlighting strategies that range from vascular disruption to vascular promotion. The biological foundation of tumor angiogenesis is discussed, with a focus on the molecular mechanisms that regulate this process, including key players such as VEGF, HIFs, and non-coding RNAs. Current therapeutic strategies, including anti-angiogenic agents, vascular normalization approaches, and emerging vascular promotion therapies, are analyzed for their clinical applications and limitations. Additionally, the review examines combination strategies that integrate anti-angiogenic therapy with chemotherapy, immunotherapy, and other modalities to enhance efficacy and overcome resistance. Despite significant progress, challenges such as drug resistance, tumor heterogeneity, and adverse effects remain. Future research directions emphasize the discovery of novel molecular targets, development of personalized treatments, and innovative combination therapies to optimize outcomes for patients with GI tumors. This comprehensive review provides a foundation for advancing angiogenesis-targeted therapies in GI cancer treatment.

Members of the genus Fomitopsis are medicinal mushrooms and a rich source of bioactive compounds with significant pharmacological and biotechnological potential. This paper provides a comprehensive review of their secondary metabolites, including polysaccharides, terpenoids, and phenolic compounds. In addition, their chemical structures and biological activities are described in detail. These compounds exhibit antioxidant, antimicrobial, anti-inflammatory, and immunomodulatory properties, with promising applications in cancer therapy, cardiovascular health, and immune modulation. Beyond medicine, Fomitopsis plays a crucial role in biotechnology, contributing to bioremediation, biofuel production, pharmaceutical development, and functional food innovation. By integrating traditional medicinal knowledge with recent scientific advances, this review highlights the biomedical significance and industrial relevance of Fomitopsis, underscoring its expanding role in health and environmental sustainability.

Staphyloxanthin (STX) is a secondary metabolite pigment associated with membrane structures, recognized for its significant antioxidant properties. It plays a crucial role in combating reactive oxygen species (ROS), positioning it as a promising and effective alternative in cancer treatment. This study focused on enhancing the production of STX pigment by employing statistical optimization of media components, alongside the evaluation of its safety and anticancer properties.

In this study, we synthesized and characterized novel brominated methoxyquinolines (7 and 11) and nitrated bromoquinoline (17) derivatives with potential antiproliferative activity against cancer cell lines. Starting from 1,2,3,4-tetrahydroquinoline (THQ, 1), a series of brominated quinoline compounds was obtained via regioselective bromination and subsequent reactions. The structure of the key compound, 3,5,6,7-tetrabromo-8-methoxyquinoline (7), was confirmed using 1D and 2D NMR techniques. Additionally, unexpected bromination of 3,6,8-trimethoxyquinoline (5) yielded 5,7-dibromo-3,6-dimethoxy-8-hydroxyquinoline (11), allowing functionalization of both rings in the quinoline. The direct nitration of 6,8-dibromoquinoline (6) yielded the corresponding 5-nitro derivative (17), a precursor to amino derivatives that activate the bromine group on the ring. Antiproliferative activities of these derivatives (7, 11, 17) were assessed against C6, HeLa, and HT29 cancer cell lines using the BCPE assay. Compounds 7, 11, and 17 exhibited significant inhibitory effects, with compound 11 showing the highest activity (IC50 values of 5.45-9.6 μg/mL). Furthermore, the cytotoxicity of these compounds was evaluated using the LDH assay, indicating lower cytotoxic effects compared to the control drug 5-FU. The ability of compounds 11 and 17 to induce apoptosis was confirmed through DNA laddering, while compound 7 showed no such effect. Compounds 7 and 11 inhibited human topoisomerase I, a critical enzyme for DNA replication and repair, with significant binding energies determined by MM-PBSA studies. The wound healing assay demonstrated that compound 17 effectively inhibited the migration of HT29 cells. These findings highlight the potential of these novel quinoline derivatives as effective anticancer agents, warranting further investigation into their mechanisms of action and therapeutic applications.

Dasatinib-related pulmonary arterial hypertension is a rare complication of chronic therapy for hematological malignancies. Pulmonary hypertension often persists despite drug discontinuation and might require vasodilators. Normalizing pulmonary hemodynamics and avoiding the long-term use of vasodilators is challenging.

In the therapeutic landscape of colorectal cancer (CRC), chemo-resistance poses a significant and prevalent obstacle that complicates treatment efficacy and patient outcomes. Over time, cancer cells can develop mechanisms to resist the toxic effects of chemo-therapy drugs, leading to reduced sensitivity or complete insensitivity to these agents. The enzyme Arylamine N-acetyltransferase 1 (NAT1) has emerged as a promising target in strategies aimed at overcoming this challenge. NAT1 is involved in the metabolism of various xenobiotics, including some chemotherapeutic agents. Understanding the complex interactions between NAT1 and chemotherapeutic agents, as well as the molecular mechanisms underlying chemo-resistance, is crucial for the development of novel therapeutic approaches.

Immunotherapy, particularly anti-PD-1 therapy, has assumed a progressively significant position in the management of non-small cell lung cancer (NSCLC), especially in lung adenocarcinoma (LUAD). Nevertheless, a subset of patients exhibit resistance to anti-PD-1 therapy, and the exploration of biomarkers for evaluating the responsiveness to anti-PD-1 therapy necessitates further investigation. FLT3LG is regarded as being associated with tumor diagnosis and immunotherapy in a variety of tumor types, but its function in LUAD is uncertain.

The burden of retinal vascular and degenerative diseases on patients and healthcare systems can be significant if patients do not complete scheduled intravitreal injections. This study aimed to identify the factors that influence adherence with follow-up injections in patients with diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion receiving intravitreal injections of anti-vascular endothelial growth factor treatment.

Chemoresistance and tumor relapse remain major clinical problems. Evidence indicates that COX2/PGE2/EP axis has a critical role in tumorogenesis and chemoresistance. This study assessed the relation of the COX-2 gene expression with chemoresistance in colon cancer (CC) patients. Also, it explored the effect of chemotherapy on COX-2 expression. The study included 24 patients with CC without chemotherapeutic treatment and 24 chemoresistant CC patients. Tumor and adjacent non-neoplastic colon tissue samples were collected and COX-2 mRNA expression was measured. Also, COX-2 and its related genes; TROP2 and DUSP4 expression were analysed in 5 flurouracil and Oxalliplatin treated Caco-2 and SW-620 cells. The results indicated significant upregulation of COX-2 expression in tissues of chemoresistant CC patients when compared with that in CC tissues without chemotherapy (p < 0.001). There was a relation between COX-2 expression with lymph nodes, metastases and staging in both groups. Concerning in-vitro experiments, there was a dose dependent significant increase of COX-2, TROP2 and DUSP4 mRNA and protein expression levels in 5flurouracil and Oxalliplatin treated cells. These findings demonstrated that overexpression of COX-2 in the chemoresistant CC patients. Both 5 flurouracil and Oxalliplatin induced COX-2 overexpression and in turn COX-2 upregulation may decrease the response of cancer to chemotherapy.

This review article offers a literature search of the most active, new copper (II) anticancer complexes based on nitrogen-containing ligands, reported in the literature over the past 5 years: from the beginning of 2019, until mid-2024. In the modern world, cancer remains one of the deadliest diseases of all. Although years of the ongoing research allowed us to better understand its nature, and thus aim more precisely at specific molecular targets and pathways, many of its aspects remain unclear. Today, chemotherapy still remains at the forefront of cancer treatment. With the ever-growing struggles to overcome chemoresistance and occurrence of serious side effects, the discovery of new, more selective and active drugs is a task of an utmost importance. At the same time, copper (II)-based compounds offer a wide array of biological activities and valuable biochemical properties. This review article provides the update on the recent advances in the discovery of new potential anticancer drugs among copper (II)-based compounds in the recent five years.