Although the efficacy of trifluridine/tipiracil hydrochloride (TAS-102) in treating metastatic colorectal cancer (mCRC) is well established, its non-hematologic toxicities in relation to renal function remain unclear. This study aimed to assess the impact of creatinine clearance (Ccr) on non-hematologic toxicities, including nausea and vomiting, in patients with mCRC treated with TAS-102.

Mitochondrial-associated granulocyte macrophage colony-stimulating factor (Magmas) is a unique protein located in the inner membrane of mitochondria, with an active role in scavenging reactive oxygen species (ROS) in cellular systems. Ovarian cancer (OC), one of the deadliest gynaecological cancers, is characterised by genomic instability, affected by ROS production in the tumour microenvironment. This manuscript discusses the role of Magmas and efficacy of its novel small molecule inhibitor BT#9 in OC progression, metastasis, and chemoresistance. Magmas expression levels were significantly elevated in high-grade human OC compared to benign tumours by immunohistochemistry. The inhibition of Magmas by BT#9 enhanced ROS production and reduced mitochondrial membrane permeability, basal respiration, mitochondrial ATP production, and cellular functions, such as the proliferation and migration of OC cell lines in vitro. Oral administration of BT#9 in vivo significantly reduced tumour growth and spread and enhanced the survival of mice without having any effect on the peritoneal organs. These data suggest that Magmas is functionally important for OC growth and spread by affecting ROS levels and that the inhibition of Magmas activity by BT#9 may provide novel clinical benefits for patients with this malignancy.

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have become a standard first-line treatment for advanced non-small cell lung cancer (NSCLC). However, the optimal sequence of administrating the two treatments remains controversial.

Conventional chemotherapeutic agents, such as 5-fluorouracil (5-FU), can exert anti-tumor effects through immunogenic cell death (ICD) induction. Researchers have found hallmarks that quantify ICD (such as the translocation of HMGB1 and calreticulin). Although chemotherapeutic agents can induce ICD, they increase the expression of immune checkpoints, limiting their effectiveness. Studies have emphasized the importance of investigating the heterogeneous responses of cells co-localized in a solid tumor (macrophages, tumor cells, etc.) to ICD induction. However, these studies were performed in vivo, which limits the collection of information on cell-cell interactions due to model complexity.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, offering life-saving benefits to tumor patients. However, the utilize of ICI agents is often accompanied by immune-related adverse events (irAEs), among which cardiovascular toxicities have attracted more and more attention. ICI induced cardiovascular toxicities predominantly present as acute myocarditis and chronic atherosclerosis, both of which are driven by excessive immune activation. Reprogramming of T cells and macrophages has been demonstrated as a pivotal factor in the pathogenesis of these complications. Therapeutic strategies targeting glycolysis, fatty acid oxidation, reactive oxygen species (ROS) production and some other key signaling have shown promise in mitigating immune hyperactivation and inflammation. In this review, we explored the intricate mechanisms underlying ICI-induced cardiovascular toxicities and highlighted the protective potential of immune reprogramming. We emphasize the roles of T cell and macrophage reprogramming in the heart and vasculature, showcasing their contributions to both short-term and long-term regulation of cardiovascular health. Ultimately, a deeper understanding of these processes will not only enhance the safety of ICIs but also pave the way for innovative strategies to manage immune-related toxicities in cancers therapy.

Immune checkpoint inhibitors (ICPIs) have emerged as a powerful strategy to cancer treatment. However, while demonstrating antitumor efficacy, they can also induce a range of immune-related adverse events (irAEs). Immune-related thyroid dysfunction is one of the most common irAEs. This study aims to investigate the clinical characteristics and identify potential risk factors associated with PD-1 inhibitor-induced immune-related thyroid dysfunction in real-world.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by enhancing T-cell-mediated immune responses against tumors. However, their use can lead to immune-related adverse events (irAEs) impacting patient outcomes. This single-center, observational study investigates the relationship between immune-related adverse events (irAEs) and survival outcomes and, to our knowledge, is the first of this kind in Polish population. Data of the 151 patients treated with ICIs, with or without chemotherapy, at the Department of Clinical Oncology and Chemotherapy in the Independent Public Hospital No. 4 in Lublin were collected from electronic medical records. Statistical analyses were performed using the Kaplan-Meier estimator, log-rank test, and multivariable Cox proportional hazard model (p < 0.05). IrAEs were observed in 38% of the patients, with the most common being thyroid dysfunction (11.9%) and dermal toxicity (6.6%). The median OS for patients with irAEs was 18.7 months, compared to 13.6 months for those without irAEs, though the difference was not statistically significant (p = 0.284). Patients with moderate toxicity had the highest median OS (26 months), while those with severe toxicity had a median OS of 6.41 months. Late-onset irAEs were associated with improved OS and PFS. Pack-years of smoking significantly impacted both OS (HR = 1.01, p = 0.014) and PFS (HR = 1.01, p = 0.011). Despite results not reaching statistical significance, the findings emphasize the clinical relevance of irAEs in treatment optimization and warrant further research to better understand their role in patient outcomes.

Solid tumours possess a hypoxic and immunosuppressive microenvironment, presenting a significant challenge to anticancer treatments. Certain anaerobic microorganisms thrive in this setting, rendering them promising candidates for targeted antitumour therapy delivery. In contrast to traditional nanodrug delivery systems, bacterial-based drug delivery systems can be engineered to produce and secrete therapeutics without the need for intricate post-purification or protective delivery methods. Nevertheless, bacteria can potentially migrate beyond their intended niche, causing off-target drug release and substantial toxicity to healthy tissues. Consequently, to enhance the effectiveness of cancer treatments while minimizing side effects, it is essential to precisely manipulate bacteria for accurate and controlled drug delivery directly to the tumour site. This can be achieved by employing inducible or repressible systems that allow for precise regulation of gene expression at specific times and locations. Ideally, engineering bacteria capable of rapidly and precisely transitioning between "on" and "off" states as required will enable them to recognize and react to targeted stimuli. While various techniques such as optical, magnetic, acoustic, and hyperbaric oxygen micromanipulation have been developed for the manipulation of particles or cells, each technique boasts its unique set of pros and cons. This review article provides an updated overview of the recent progress in the spatiotemporal control of engineered bacteria via these methods and discusses the benefits and constraints of each approach.

Methylnissolin (also known as Astrapterocarpan) is an isoflavonoid compound featuring a pterocarpan core structure. To date, leguminous plants of the genus Astragalus remain the exclusive natural source of Methylnissolin and its glycoside derivative, Methylnissolin-3-O-glucoside. Upon oral administration, Methylnissolin and its glycosides enter systemic circulation and modulate signaling pathways such as RIPK2/ASK1, PI3K/AKT, IκB/NF-κB, MAPK, and Nrf2/HO-1. Their pharmacological activities span anti-inflammatory, antioxidant, glucose-lipid metabolism regulation, and antitumor effects, underscoring their broad potential for drug development. This review comprehensively evaluates the physicochemical properties, pharmacological activities, mechanisms of action, pharmacokinetic characteristics, and toxicological profile of Methylnissolin and its glycoside derivatives. Notably, we systematically elucidate the metabolic fate of methylnissolin, identifying hydroxylation, demethylation, dimerization, hydration, and dehydrogenation as predominant biotransformation pathways. Furthermore, the influence of factors such as plant variety, geographical origin, and processing methods on Methylnissolin and its glycoside content in Astragalus membranaceus is analyzed, providing crucial insights for drug development and resource utilization.

Immune checkpoint blockade, particularly targeting programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), shows promise in treating hepatocellular carcinoma (HCC). However, acquired resistance, especially in patients with 'hot tumours', limits sustained benefits. Lysine-specific demethylase 1 (LSD1) plays a role in converting 'cold tumours' to 'hot tumours', but its involvement in PD-1 inhibitor resistance in HCC is unclear.

Everolimus is used in the treatment of breast cancer by targeting the PI3K/AKT/mTOR pathway, particularly during anti-hormonal therapy. The efficacy of everolimus is limited due to a feedback loop that supresses mTOR while simultaneously enhancing Akt activation in endocrine-resistant breast cancer. Melatonin (N-acetyl-5-methoxytryptamine) regulates mitochondrial activity, cell death, and autophagy due to its strong free radical scavenging, antioxidant, and anti-inflammatory characteristics. Melatonin, a naturally occurring oncostatic agent, slows tumor growth in a range of malignancies, including breast cancer. Due to its ability to protect healthy cells from oxidative stress and inflammation, along with its anti-cancer properties, melatonin has the potential to serve asan effective adjuvant in breast cancer therapy. It also inhibits the phosphorylation of mTOR and Akt, two essential pathways implicated in breast cancer growth, which may aid in overcoming resistance to targeted treatments like everolimus. The combination effects of melatonin and everolimus on hormone receptor-positive breast cancer remains unexplored. This study examined the effectiveness of melatonin when combined with everolimus for the treatment of hormone receptor-positive breast cancer.

Solanine has been shown to inhibit cancer by regulating the expression of apoptosis (Bax, Bcl-2) and metastasis (CDH-1, MMP2) genes in various cancer cell types. We synthesized optimized niosome NPs (NPs) with high solubility and capacity for solanine loading. In this study, the cytotoxic, cell cycle inhibitory and apoptotic effects of solanine-loaded niosome NPs (SN-NPs) on MCF-7 were investigated. Thin-layer hydration was used to generate SN-NPs and their features were validated. The pH-dependent solanine release pattern was also examined. Synthesized SN-NPs were evaluated for cytotoxicity against MCF-7 and MCF-10 cell lines using MTT. Primary and secondary apoptosis, necrosis, and cell cycle arrest were measured using flowcytometry. Lastly, q-PCR was used to assess the expression of genes. The NPs had an average size between 50 and 70 nm, with a polydispersity index (PDI) of 0.452. Solanine was effectively incorporated into noisome NPs, as shown by the high encapsulation efficiency of 82.3%±0.24%. After a quick burst at pH 7 and 5, SN-NPs released slowly and sustainedly. The IC50 of solanine-loaded niosomes against MCF-7 cells decreased from 40 mg/100 mL to 10 mg/100 mL (48 h) and 5 mg/100 mL (72 h). After 72 h, SN-NPs caused late apoptosis in 30% of MCF-7 cells and necrosis in 5.06% (p < 0.01). SN-NPs caused 81% of cells to arrest in the G0/G1 phase, with only 12% progressing to G2/M (p < 0.01). Solanine-loaded NPs significantly increased Bax and CDH-1 gene expression in malignant cells compared to free niosomes and free solanine (p < 0.0001). Bcl-2 and MMP2 expression significantly decreased in this group compared to free niosomes and free solanine (p < 0.001). Solanine-containing niosomes showed significant anticancer effects on MCF-7 breast cancer cells, which were supported by apoptosis, cell cycle arrest and regulation of gene expression. The regulated release and precise delivery of solanine using SN-NPs show considerable translational potential. This improved nanocarrier technology may increase the bioavailability and efficacy of solanine, potentially leading to improved clinical outcomes in breast cancer therapy.

This meta-analysis systematically evaluated the effectiveness and safety of immune checkpoint inhibitors (ICIs) in treating advanced cervical cancer, emphasizing their potential as transformative therapeutic options in this complex clinical landscape.

This study assessed the safety and efficacy of rechallenging patients in advanced non-small cell lung cancer (NSCLC) without targetable driver mutations using a combination of immune checkpoint inhibitors (ICIs) and anlotinib following progression after prior immunotherapy.

This study aims to evaluate the anticancer properties of chamomile nano-emulsion (Cha-NE) and α-lactalbumin (α-LA) coated Cha-NE (LA-Cha-NE) against breast tumor through both in vitro and in vivo investigations. Both Cha-NE and LA-Cha-NE exhibited typical semi-spherical forms under Transmission electron microscope (TEM), and displayed surface charges of 46.75 and 28.45 mV with average sizes of 87.46 and 112.75 nm, respectively. In a safe manner, Cha-NE and LA-Cha-NE showed higher selectivity against breast cancer (MDA-MB-231 and MCF7) cells than normal (HSF) cells. Reductions in serum contents of IL1β, TNF-α, IL-4, IL-6, IL-10, ASAT, ALAT, creatinine, urea, triglycerides, and cholesterol, as well as an the administration of LA-Cha-NE, breast tumor incidence dramatically reduced. Thus, improvement in survival rates leads to successful prevention of mammary tumorigenesis as proved by the histopathological and immunohistochemistry findings. However, there was an increase in mammary GSH, GPx, CAT, and SOD activity. Both in vitro and in vivo investigations showed that LA-Cha-NE had a beneficial therapeutic effect, exhibiting more significantly regulated apoptosis and elevated expression of genes that regulate the cell cycle. Thus, this study demonstrated that the chemo-preventive property of LA-Cha-NE may offer a brand-new alternative therapy to cure breast cancer by re-establishing the compromised oxidative stress response, enhancing the immune response, reducing inflammation process, and fortifying the apoptosis pathway.

Transarterial chemoembolization (TACE) is considered unsuitable for hepatocellular carcinoma (HCC) that exceeds up-to-7 criteria. Balloon-occluded alternative infusion of cisplatin solution and gelatin particles of transarterial chemoembolization (BOAI-TACE) has shown promise in the treatment of HCC and preservation of liver function. This prospective, single-arm study enrolled patients with HCC beyond up-to-7 criteria from five hospitals. The primary endpoint was objective response ratio (ORR) for BOAI-TACE, according to response evaluation criteria in cancer of the Liver (RECICL), at 2 months after treatment. Eighteen patients were enrolled in this study. Fourteen patients achieved response, resulting in an ORR of 77.8% (95% confidence interval [CI] 54.3-91.5%) according to both RECICL and modified response evaluation criteria in solid tumor (mRECIST) guidelines, meeting the primary endpoint. Disease control rate was 88.9% (95% CI 66.0-98.1%). No worsening of either Child-Pugh or albumin-bilirubin (ALBI) scores was observed. No serious adverse events were recorded, indicating that BOAI-TACE retains utility even in severe HCC cases while preserving liver function.

High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of epithelial ovarian cancer, often diagnosed at advanced stages with a poor prognosis. Paclitaxel (PTX), a standard chemotherapeutic agent for HGSOC, exerts cytotoxic effects on cancer cells and modulates the tumor microenvironment. This study aimed to elucidate the molecular mechanisms of PTX in HGSOC using bioinformatics, machine learning, network pharmacology, and molecular docking, to identify potential diagnostic biomarkers and therapeutic targets. We identified differentially expressed genes (DEGs) between HGSOC and normal ovarian tissues using the GSE54388 dataset from the Gene Expression Omnibus database. The intersection of these DEGs with PTX targets, identified from the Swiss Target Prediction database, yielded 15 overlapping genes. These genes were analyzed via protein-protein interaction (PPI) network analysis to identify significant interaction relationships. Kaplan-Meier survival analysis was then performed to assess the prognostic significance of these genes. Their protein expression patterns in HGSOC tissues were validated using the Human Protein Atlas (HPA) database. Functional enrichment analysis was conducted using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. A combined diagnostic model was developed using LASSO regression and validated in two independent external datasets (GSE26712 and GSE12470). Molecular docking experiments were conducted to confirm the binding affinity of PTX to key proteins. Immune infiltration analysis was performed to assess the tumor microenvironment, revealing significant differences in immune cell composition between normal and tumor tissues. A total of 2267 DEGs were identified, with 15 overlapping genes related to PTX targets. After PPI network analysis, Kaplan-Meier survival analysis, and HPA validation, five key genes (AURKA, CBX7, CCNA2, HSP90AA1, and TUBB3) were identified as associated with HGSOC progression. The combined diagnostic model demonstrated high accuracy in distinguishing HGSOC from normal tissues, with AUC values of 0.9892 and 0.9465 in the GSE26712 and GSE12470 validation datasets, respectively. Molecular docking confirmed stable binding of PTX to these key proteins, suggesting their role in PTX's therapeutic effects. Immune infiltration analysis revealed significant differences in immune cell composition between normal and tumor tissues, highlighting the potential impact of these genes on the tumor microenvironment. In summary, our findings provide a theoretical basis for improving clinical diagnosis and elucidating the underlying mechanisms of HGSOC.

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare yet highly lethal kidney cancer. To deepen our understanding of FH-deficient RCC, we conduct a comprehensive integrated genomic study. We analyze the association of FH alteration patterns with tumor heterogeneity and develop a CpG site-specific methylation signature for precise identification of FH-deficient RCC. Transcriptomic analysis unveils three distinctive molecular subtypes characterized by enrichment of immune/Angiogenic/Stromal (C1), WNT/Notch/MAPK (C2), and proliferation/stemness (C3) pathways, respectively. Tumors in C1 derive the most substantial survival benefit from a combination of immune checkpoint blockade (ICB) and anti-angiogenic therapy. Tumors in C2 display moderate response to this therapeutic approach. In contrast, tumors in C3 exhibit an unfavorable response to anti-angiogenic monotherapy and its combination with ICB. These findings contribute to a profound understanding of the aggressive nature of FH-deficient RCC, offering insights into potential precision medicine approaches for disease management.

Polo-like kinase 1 (PLK1) signaling drives tumor malignancy and chemotherapy resistance, which is an unmet clinical need. Recruiting PLK1 to the central spindle during anaphase is necessary for its function in promoting cancer cell proliferation, which is achieved by binding to microtubule-associated protein regulating of cytokinesis (PRC1) located in the spindle. However, the role of PLK1/PRC1 signaling in chemotherapy resistance is unknown. In this study, we identified a small molecule B4 which inhibited PLK1/PRC1 signaling through disrupting the formation of PLK1/PRC1 protein complexes. In the presence of blocking PLK1/PRC1 signaling, enhanced sensitivity of drug-resistant tumors to traditional chemotherapy was found. Suppression of PLK1 activity by B4 inhibited disease progression in allograft models, and combination with cisplatin elicited dramatic regression of drug-resistant tumors. Our findings provide a promising strategy to target the PLK1 signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in non-small cell lung cancer (NSCLC).

Immune checkpoint inhibitors (ICIs) have led to enduring responses in subsets of patients with cancer. However, these responses carry the risk of immune-related adverse events (irAEs), which can diminish the overall benefit of ICI treatment. While associations between irAE development and overall survival have been increasingly documented, there is a need for further understanding of these connections in large prospective real-world cohorts.