Search Results (367)

Background/Objectives: Alectinib, a second-generation tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer (NSCLC), exhibits suboptimal oral bioavailability, primarily attributable to its inherently low aqueous solubility and limited dissolution kinetics. This study aimed to enhance Alectinib’s solubility and therapeutic efficacy by formulating a G4-NH2-PAMAM dendrimer complex. Methods: The complex was prepared using the organic solvent evaporation method and characterized by DSC, FTIR, dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with the G4-NH2-PAMAM dendrimer complex. Cytotoxicity against NSCLC cell line A549 was assessed using MTT assays, clonogenic assay, and scratch-wound assay. Xenograft effect was investigated in the H460 lung cell line. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: Alectinib exhibited an encapsulation efficiency of 59 ± 5%. In vitro release studies demonstrated sustained drug release at pH 6.8 and faster degradation at pH 2.5. Anticancer activity in vitro showed comparable efficacy to free Alectinib, with 98% migration inhibition. In vivo tumor suppression studies revealed near-complete tumor regression (~100%) after 17 days of treatment, compared to 75% with free Alectinib. Pharmacokinetic analysis indicated enhanced absorption (shorter Tmax), prolonged systemic circulation (longer half-life), and higher bioavailability (increased AUC) for the dendrimer-complexed drug. Conclusions: These findings suggest that the G4-NH2-PAMAM dendrimer system significantly improves Alectinib’s pharmacokinetics and therapeutic potential, making it a promising approach for NSCLC treatment. Full article

Background: Oral squamous cell carcinoma (OSCC) is one of the most serious forms of cancer in the world. The opportunities to decrease the mortality rate would lie in the possibility of earlier identification of this pathology, and at the same time, the immediate approach of anticancer therapy. Furthermore, new treatment strategies for OSCC are needed to improve existing therapeutic options. Bioactive compounds found in medicinal plants could be used to support these strategies. It is already known that they have an increased potential for action and a safety profile; therefore, they could improve the therapeutic effect of classical chemotherapeutic agents in combination therapies. Methodology: This research was based on an extensive review of recently published studies in scientific databases (PubMed, Scopus, and Web of Science). The selection criteria were based on experimental protocols investigating molecular mechanisms, synergistic actions with conventional anticancer agents, and novel formulation possibilities (e.g., nanoemulsions and mucoadhesive films) for the targeted delivery of bioactive compounds in OSCC. Particular attention was given to in vitro, in vivo, translational, and clinical studies that have proven therapeutic relevance. Results: Recent discoveries regarding the effect of bioactive compounds in the treatment of oral cancer were analyzed, with a view to integrating them into oncological practice for increasing therapeutic efficacy and reducing the occurrence of adverse reactions and treatment resistance. Conclusions: Significant progress has been achieved in this review, allowing us to appreciate that the valorization of these bioactive compounds is emerging. Full article

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide, with oral squamous cell carcinoma (OSCC) accounting for a significant portion of cases. Despite advancements in treatment, only modest gains have been made in HNSCC/OSCC control. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have emerged as targeted therapies for OSCC in clinical trials. However, their clinical efficacy remains a challenge. Cannabidiol (CBD), a non-psychoactive phytochemical from cannabis, has demonstrated anticancer and immunomodulatory properties. CBD induces apoptosis and autophagy and modulates signaling pathways often dysregulated in HNSCC. This review summarizes the molecular mechanisms of EGFR-TKIs and CBD and their clinical insights and further discusses potential implications of combination targeted therapies. Full article

Background: Doxorubicin (DOX) is a potent anti-cancer agent that is widely described in cancer treatment. However, its administration is often limited by its adverse effects, particularly its testicular toxicity, which can induce infertility in male patients. DOX-induced testicular damage is due to oxidative stress, apoptosis, and inflammation. Nanocurcumin (NCR) is a nano-formulated edition of curcumin with a higher therapeutic potential. NCR has demonstrated antioxidant and anti-inflammatory properties. Methods: This study is designed to inspect the potential validity of NCR on DOX-induced testicular damage in male rats. We used thirty-two Wistar albino rats (150–200 g) and divided them into four groups. NCR (80 mg/kg/ dissolved in 1% CMC) was given orally by oral gavage for 14 days. A single dose of DOX (15 mg/kg) (i.p.) was injected on the 7th day of the experiment. Results: DOX treatment reduced the sperm viability and motility rate, cellular antioxidants, and gonadal hormones; it led to higher levels of inflammatory mediators, necrosis, and sloughing in seminiferous tubules. Conversely, NCR treatment significantly alleviated these side effects by improving sperm count/motility and reducing sperm abnormalities. The testicular function recovery was likely driven by stimulating the cytoprotective SIRT1/NF-κB pathway, depressing the testicular level of oxidative indicators such as MDA, TNF-α, iNOS, IL-1β, and NO, and increasing levels of antioxidants such as GSH and SOD. In addition, NCR contradicted the apoptotic changes by downregulating the pro-apoptotic signals Bax and caspase-3, while inducing Bcl-2 upregulation. Moreover, NCR increased levels of gonadal hormones, attenuated histological abnormalities, and preserved testicular structure when compared with the DOX group. Conclusions: NCR treatment can effectively ameliorate DOX-induced testicular toxicity. Full article

Curcumin-mediated photodynamic therapy (PDT) has emerged as a promising approach for targeting oral squamous cell carcinoma (OSCC), a malignancy with a rising incidence. This systematic review synthesizes evidence from in vitro studies evaluating the anticancer efficacy of curcumin as a photosensitizer in PDT against OSCC cells. A comprehensive literature search across four databases identified eight eligible studies published between 2009 and 2024. The findings demonstrated that curcumin-PDT reduces OSCC cell viability, induces apoptosis, and impairs metabolic activity, particularly when curcumin is delivered via nanocarriers and activated with light sources near its absorption peak (430–457 nm). Despite methodological heterogeneity across cell lines, curcumin formulations, and light parameters, the photodynamic effects were reproducible and showed low dark toxicity. However, the lack of standardized protocols and absence of in vivo or clinical validation limit translational potential. Further preclinical research is needed to optimize treatment conditions and assess safety and efficacy in biological systems that more closely resemble the clinical environment. Full article

Mammary gland tumors in dogs are very common in clinical practice. Betulinic acid is currently a compound considered to have anticancer properties in human mammary tumors via nanoemulsions. In this study, betulinic acid nanoemulsions with a particle size of less than 300 nm were prepared. Biopsies were obtained from five female dogs with mammary tumors for histopathological analysis, confirming that two were tubular mammary carcinomas (MMTs, malignant) and three were complex mammary adenomas (BMTs, benign). The five female dogs were administered with a daily oral dose of nanoemulsion containing 5 mg/kg of betulinic acid for 30 days. Tumor size was measured every 7 days, and the response to treatment was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors) standards. In one of the females with MMTs treated with the nanoemulsion, the tumor size was reduced by approximately 38%, while in the BMT female dogs, the nanoemulsion reduced the tumor size by 25.3%. It was concluded that oral administration of betulinic acid nanoemulsions reduced the size of canine mammary tumors. Experimental studies are still needed to further evaluate this preparation. Full article

Background: Colorectal cancer (CRC) is the third most common cancer globally. Atorvastatin (ATR), a lipid-lowering drug, has shown promise as a repurposed therapeutic agent for CRC. However, its clinical application is limited by poor solubility and low oral bioavailability. This study aimed to optimize ATR-loaded chitosan-coated cubosomes using a Box–Behnken design and evaluate their potential in CRC treatment through physicochemical characterization and cell viability studies on HCT116 human CRC cells. Methods: Optimized cubosomes were characterized for particle size, zeta potential, polydispersity index (PDI), drug content, entrapment efficiency, compatibility using Fourier transform infrared spectroscopy, and in vitro release in various pH media. Cytotoxic effects were assessed using sulforhodamine B and trypan blue viability assays. Results: Uncoated cubosomes exhibited a particle size of 120.0 ± 1.66 nm, a zeta potential of −22.2 ± 1.05 mV, and a PDI of 0.136 ± 0.01. The chitosan-coated cubosomes displayed a size of 169.3 ± 4.14 nm, a zeta potential of 29.7 ± 0.814 mV, and a PDI of 0.245 ± 0.015. Entrapment efficiency and drug content were 92.1 ± 2.46% and 64.5 ± 1.58%, respectively. The ATR-loaded cubosomes demonstrated pH-dependent release, negligible at pH 1.2 and 4.5, but pronounced at pH 6.8 and 7.4, supporting colon-targeted delivery. Cell viability studies showed significant inhibition of HCT116 cells at ATR concentrations of 1 and 5 µM, with complete inhibition at higher doses. Conclusions: Chitosan-coated ATR-loaded cubosomes are promising for targeting ATR delivery to the colon. They offer enhanced anticancer activity by bypassing gastric degradation and systemic circulation, making an efficient approach to CRC treatment. Full article

Background/Objectives: Breast cancer continues to be a major global health challenge, driving the urgent need for innovative therapeutic strategies. This study evaluates the anticancer and immunomodulatory potential of skimmianine in breast cancer through a comprehensive approach, integrating biochemical, histopathological, immunohistochemical, and bioinformatics analyses. Methods: Thirty-six female Wistar albino rats were divided into three groups: control, 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast cancer, and DMBA + skimmianine (n = 12/group). Breast cancer was induced with a single oral dose of 50 mg/kg DMBA in sesame oil. After 16 weeks, skimmianine (40 mg/kg) was administered intraperitoneally for four weeks. Serum CA15-3 levels were measured via enzyme-linked immunosorbent assay (ELISA). Histopathological assessment was performed using hematoxylin and eosin (H&E) staining, and proliferating cell nuclear antigen (PCNA) and tumor necrosis factor-alpha (TNF-α) were evaluated immunohistochemically. Pathway and hub gene analyses were performed using Cytoscape, functional annotation with Enrichr, and immune analyses via the Tumor and Immune System Interaction Database (TISIDB) and Sangerbox. Results: The tumor burden in the animals increased after DMBA induction compared to the control groups (0.00 ± 0.00% vs. 89.00 ± 6.60%, respectively, p < 0.001), while skimmianine treatment significantly reduced the tumor burden in the animals (49.00 ± 9.40%, vs. DMBA group, p = 0.191). Histopathological analysis showed DMBA-induced structural disorganization and malignant clustering, whereas skimmianine preserved ductal structures and mitigated the damage. Compared to the control group, DMBA administration markedly elevated serum CA15-3 levels (0.23 ± 0.06 ng/mL vs. 8.57 ± 1.01 ng/mL, respectively), along with PCNA (13.0 ± 3.0% vs. 25.0 ± 4.0%, respectively) and TNF-α (8.4 ± 1.7% vs. 34.0 ± 5.3%, respectively) expression, indicating active tumor progression. Skimmianine treatment significantly reduced CA15-3 (3.72 ± 0.58 ng/mL), PCNA (20.0 ± 4.1%), and TNF-α (25.0 ± 3.9%) levels (p < 0.001). In silico analyses indicated skimmianine’s effects on PCNA influence cell cycle pathways, while TNF-α suppression impacts toll-like receptor (TLR) signaling (adjusted p < 0.05). PCNA- and TNF-α-related anticancer effects were especially notable in basal molecular and C2 immune subtypes (p < 0.05). Related hub proteins may regulate immune dynamics by reducing immunosuppression and tumor-promoting inflammation (p < 0.05). Conclusions: Skimmianine shows promise as a breast cancer therapy by simultaneously targeting tumor growth and immune regulation, with PCNA and TNF-α identified as potential key players. Full article

Searching for new anticancer drugs is a significant challenge for the medical community due to the current limitations of existing treatments. The primary objective of this study was to design and optimize multi-targeted drug candidates based on a quinoline scaffold. In this paper, we adopt various in silico techniques, including molecular docking, molecular dynamics simulations, and ADMET property modeling, to predict the binding affinity and interactions of 7-ethyl-10-hydroxycamptothecin derivatives with multiple biological targets. The interactions of these compounds with three potential molecular targets, topoisomerase I, bromodomain-containing protein 4, and ATP-binding cassette sub-family G member 2 proteins, were analyzed. It has been previously proved that the inhibition of these molecular targets may have beneficial effects on cancer treatment. The designed chemical compounds can effectively interact with selected proteins, thereby establishing their potential as drug candidates. Molecular docking revealed promising binding affinities, with topoisomerase I docking scores ranging from −9.0 to −10.3 kcal/mol, BRD4 scores from −6.6 to −8.0 kcal/mol, and ABCG2 scores from −8.0 to −10.0 kcal/mol. Furthermore, the ADMET property analysis indicates promising pharmacological profiles, protein binding affinity, selectivity, and bioavailability while minimizing toxicity. For example, satisfactory logP values have been demonstrated in the favorable range for bioavailability after oral administration. Additionally, several compounds exhibited predicted aqueous solubility values greater than −3, suggesting moderate-to-good solubility, which is crucial for oral drug delivery. Full article

Objectives: The multidisciplinary city-hospital Oncoral follow-up of cancer outpatients has been set up to ensure the safety of oral anticancer drugs (OADs). The aim of this study was to assess Oncoral by Relative Dose Intensity (RDI) in patients with hematological malignancies treated with ibrutinib as a model. Methods: The study included all outpatients treated with ibrutinib and followed in Oncoral between January 2016 and June 2020. Patients benefited from interviews leading to pharmacist and nurse interventions (PNI) on drug-related problems as adverse events (AE), drug–drug interactions (DDI), and drug intake. Results: In total, 83 patients were enrolled. At least one PNI was performed for 86.7%, focusing on drug intake and DDIs (54.5%), the management of AEs (27.0%), and community–hospital coordination (18.5%). Major DDIs with ibrutinib were found in 10 patients, with at least one moderate interaction in 28%. Grade 3–4 AEs mainly concerned cytopenia and infection. Adherence tended to decrease after the first 6 months. At 6 months, the mean RDI was 93.7 ± 11.3%; RDI reductions occurred in 43% patients. RDI was lower in patients who discontinued treatment before day 90 and worsened over time in patients still being treated at month 6 (Friedman’s test, p < 0.01). Age and gender were predictors of early treatment termination (OR 1.10 [1.03; 1.19] and 6.44 [1.65; 37.21]). The estimates of 30-month OS and PFS were 73.8% (95% CI [64.7%; 84.2%]) and 61.8% (95% CI [51.8%; 73.7%]). Conclusions: The Oncoral follow-up is a secure, coordinated pathway assessed by RDI. Multidisciplinary follow-up should be the gold-standard for outpatients receiving OADs. Full article

Approaches capable of simultaneously treating cancer and protecting susceptible patients from lethal infections are highly desirable, although they prove challenging. Taking inspiration from the well-known anticancer platinum complexes, successive studies about the complexation of organic compounds with other late transition metals, such as silver, gold, palladium, rhodium, ruthenium, iridium, and osmium, have led to remarkable anticancer activities. Among the numerous chemical moieties studied, N-heterocyclic carbenes (NHCs) have revealed very attractive activities due to their favorable chemical properties. Specifically, gold–NHC complexes emerged as some of the most active complexes acting as antitumor agents. On the other hand, some recent studies have highlighted the involvement of these complexes in antiviral research as well. The well-known gold-based, orally available complex auranofin approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis has been suggested as a repositioned drug for both cancer and viral infections. In the era of the COVID-19 pandemic, the most interesting goal could be the discovery of gold–NHC complexes as dual antiviral and anticancer agents. In this review, the most recent studies regarding the anticancer and antiviral activities of gold(I)–NHC complexes will be analyzed and discussed, offering an interesting insight into the research in this field. Full article

Introduction: Decursin is a pyranocoumarin natural phytochemical found in the Angelica gigas Nakai herb, which shows various therapeutic properties and beneficial effects against various diseases. Objective: The aim of this study was to find the anticancer potential of decursin and its molecular mechanisms involved with different anticancer effects. Methodology: All of the relevant data concerning this compound and cancer were collected using different scientific search engines, including PubMed, Scopus, Springer Link, Wiley Online, Web of Science, Scifinder, ScienceDirect, and Google Scholar. Results: This study found that decursin shows anticancer properties through various mechanisms, such as apoptosis, cell cycle arrest, inhibition of cell proliferation, autophagy, inhibition of angiogenesis, cytotoxicity, and the inhibition of invasion and migration against a number of cancers, including breast, bladder, lung, colon, skin, ovarian, prostate, pancreatic, and bone cancers. This study also discovered that decursin has the ability to affect several signaling pathways in the molecular anticancer mechanisms, such as the PI3K/AKT/mTOR, JAK/STAT, and MAPK signaling pathways. Findings also revealed that decursin expresses poor oral bioavailability. Conclusions: Based on the data analysis from this literature-based study, decursin has properties to be considered as a potential candidate in the treatment of cancer. However, more clinical research is suggested to establish proper efficacy, safety, and human dosage. Full article

Hypoxic tumors pose considerable obstacles to cancer treatment, as diminished oxygen levels can impair drug effectiveness and heighten therapeutic resistance. Oral cancer, a prevalent malignancy, encounters specific challenges owing to its intricate anatomical structure and the technical difficulties in achieving complete resection, thereby often restricting treatment efficacy. The impact of hypoxia is particularly critical in influencing both the treatment response and prognosis of oral cancers. This article summarizes and examines the potential of polymer nanomedicines to address these challenges. By engineering nanomedicines that specifically react to the hypoxic tumor microenvironment, these pharmaceuticals can markedly enhance targeting precision and therapeutic effectiveness. Polymer nanomedicines enhance therapeutic efficacy while reducing side effects by hypoxia-targeted accumulation. The article emphasizes that these nanomedicines can overcome the drug resistance frequently observed in hypoxic tumors by improving the delivery and bioavailability of anticancer agents. Furthermore, this review elucidates the design and application of polymer nanomedicines for treating hypoxic tumors, highlighting their transformative potential in cancer therapy. Finally, this article gives an outlook on stimuli-responsive polymeric nanomedicines in the treatment of oral cancer. Full article

Ephedrine alkaloids-free Ephedra Herb extract (EFE) was developed to reduce the adverse effects of Ephedra Herb, a constituent drug in Kampo medicines. It is produced by decocting Ephedra Herb with hot water and excluding the ephedrine alkaloids. EFE has analgesic and anti-cancer effects and inhibits respiratory viruses in vitro. To assess the pharmacological action of EFE in vivo, we evaluated its effect on the replication of murine hepatitis virus (MHV), a coronavirus that causes hepatitis, pneumonia, and severe acute respiratory syndrome-like symptoms, within infected mice. On Day 0, MHV was inoculated intranasally into female BALB/C mice, and EFE was orally administered once/day at 350–700 mg/kg (n = 10/group) starting 1 h after inoculation until Day 5. Through a plaque assay, MHV was detected on Day 5 in the lung and liver in all inoculated mice, but the titer was significantly lower in the EFE groups as compared with untreated control mice. Although not statistically significant, the clinical score for respiratory irregularity tended to be lower in the EFE treatment groups. In conclusion, EFE inhibits MHV replication in an in vivo mouse model of human coronavirus infection and exerts pharmacological action in the lung and liver. Full article

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer in the head and neck region. In advanced stages of OSCC, chemotherapy is commonly used for treatment, despite some cancer cells having low sensitivity to anticancer drugs. We focused on RBM17/SPF45 as an essential drug-sensitizing factor in the context of malignant cells acquiring chemoresistance. Here, we demonstrate how RBM17 affects anticancer drug resistance in OSCC and we suggest the possible mechanism underlying its effects. After exposing oral cancer cell lines to fluorouracil (5-FU) and cisplatin, but not paclitaxel, the gene and protein expression of RBM17 increased. We found that siRNA-mediated RBM17-knockdown of the cell lines gained a significantly higher sensitivity to 5-FU, which was remarkably followed by a decrease in the expression of checkpoint kinase 1 (CHEK1) protein, whereas treatment with a CHEK1 inhibitor did not affect RBM17 protein expression in the oral cancer cell lines. These results indicate that RBM17 is a factor involved in the development of resistance to cytotoxic chemotherapy. We propose the underlying mechanism that RBM17 promotes CHEK1 protein expression in the ATM/ATR pathway, triggering the development of chemoresistance in cancer cells. Full article