In 2017, reports of adverse drug reactions worldwide reached an estimated 35 million.Chemotherapeutic agents were one of the most often implicated pharmacological classes in inducing adverse drug reactions. Adverse drug reactions increase the overall expense and mortality. Adverse drug reactions increase morbidity, mortality, hospitalization rate and financial expenses. Therefore, this study intended to assess chemotherapy-related adverse drug reactions and associated factors among adult cancer patients.

A 74-year-old woman with chronic myeloid leukemia on long-term imatinib therapy and a history of bisphosphonate use presented with an atypical femoral fracture after low-energy trauma. She underwent staged intramedullary nailing of both femurs.

Glioblastomas utilize malignant gene expression pathways to drive growth. Many of these gene pathways are not directly accessible with molecularly targeted pharmacological agents. Chromatin-modifying compounds can alter gene expression and target glioblastoma growth pathways. In this study, we utilize a systematic screen of chromatin-modifying compounds on a panel of patient-derived glioblastoma lines to identify promising compounds and their associated gene targets.

Abiraterone acetate has established itself as an effective treatment for metastatic castrate-resistant prostate cancer (mCRPC). However, disease progression remains inevitable with conventional long-term maximum tolerated dose (MTD) therapy due to the development of drug resistance. Adaptive therapy (AT), rooted in Darwinian evolutionary dynamics, offers a novel approach to combat drug resistance. By dynamically adjusting drug doses, AT aims to enhance treatment outcomes. Despite successful clinical trials and extensive theoretical studies on AT, significant challenges persist in determining optimal adaptive therapeutic schedules tailored to individual patients. This study presents a biochemically motivated mathematical model incorporating competition between drug-sensitive and drug-resistant cancer cells, incorporating mutated migration factors identified through prostate-specific antigen (PSA) data. Theoretical analyses, including the stability of equilibrium states and the existence of periodic solutions, validate the model's interpretability and support the feasibility of adapted periodic therapy. We propose an optimal adaptive periodic therapy framework, formulating a bilevel dynamic optimization problem with constraints to establish personalized adaptive therapeutic schedules for prostate cancer. Optimal solutions identify therapeutic switches and doses under adaptive therapy. We compare our proposed framework with other adaptive strategies regarding overall survival and total drug doses through numerical simulations and quantitative analysis, demonstrating superior performance. Our model presents a promising tool for integration into clinical research trials, offering individualized adaptive therapeutic schedules to enhance precision management of mCRPC.

Disease modeling is vital for our understanding of disease mechanisms and for developing new therapeutic strategies. Accurately modeling the intact tumor microenvironment (TME) is increasingly recognized as essential for gaining insights into cancer biology and therapeutic response. Preclinical mouse models have provided utility for studying the evolving TME, but these models are costly and can lead to animal suffering and the discontinuation of drug investigations. To address these limitations, particularly in hepatocellular carcinoma (HCC), we have developed an ex vivo model using tumor precision-cut slices (TPCS) derived from orthotopic liver tumors.

Tamoxifen, a commonly used selective estrogen receptor antagonist for adjuvant therapy in hormone receptor-positive breast cancer, can cause ocular side effects due to estrogen receptors in ocular structures. This prospective study explores its impact on ocular morphology and function.

&lt;b&gt;Background and Objective:&lt;/b&gt; Endophytic actinomycetes represent a promising source of novel bioactive compounds. This study aimed to isolate and characterize endophytic actinomycetes from &lt;i&gt;Aloe vera&lt;/i&gt; leaves, identify their bioactive metabolites and assess their antimicrobial and anticancer properties. &lt;b&gt;Materials and Methods:&lt;/b&gt; Endophytic actinomycetes were isolated from &lt;i&gt;Aloe vera&lt;/i&gt; leaf sections and screened for antimicrobial activity. Isolate AVL08, exhibiting potent activity against &lt;i&gt;Staphylococcus aureus&lt;/i&gt;, was identified using 16S rRNA gene sequencing and morphological characterization. Bioactive compounds were extracted, purified and identified using spectroscopic methods. Antimicrobial activity was evaluated using microbroth dilution assays and cytotoxicity was assessed against Vero, HeLa, HepG2 and MDA-MB-231 cell lines. Molecular docking studies were performed to investigate interactions with human DNA topoisomerase II. &lt;i&gt;In silico&lt;/i&gt;, ADMET predictions were conducted using SwissADME, PreADMET and pkCSM. Statistical analysis was performed using SPSS (version 11.01) with One-way ANOVA and Tukey's &lt;i&gt;post hoc&lt;/i&gt; test, considering differences significant at p<0.05. &lt;b&gt;Results:&lt;/b&gt; Isolate AVL08 was identified as &lt;i&gt;Streptomyces galbus&lt;/i&gt; and produced two anthraquinone compounds, 1,4,6-trihydroxy-8-(2'-oxopentyl)-9,10-anthraquinone (&lt;b&gt;1&lt;/b&gt;) and 1,4,6-trihydroxy-8-pentacarboxyl-9,10-anthraquinone (&lt;b&gt;2&lt;/b&gt;). These compounds exhibited selective antibacterial activity against Gram-positive bacteria and significant cytotoxicity against MDA-MB-231 and HeLa cancer cell lines, with IC&lt;sub&gt;50&lt;/sub&gt; values ranging from 94.00 to 154.52 μg/mL. Compound &lt;b&gt;2&lt;/b&gt; demonstrated enhanced potency and selectivity against HepG2 cells. Molecular docking revealed favorable interactions of the anthraquinones with topoisomerase II. The ADMET predictions indicated favorable pharmacokinetic profiles but highlighted potential hERG channel inhibition and mutagenicity in specific bacterial strains. &lt;b&gt;Conclusion:&lt;/b&gt; &lt;i&gt;Streptomyces galbus&lt;/i&gt; AVL08 is a promising source of bioactive anthraquinones with potent antimicrobial and anticancer properties. The identified compounds, particularly Compound &lt;b&gt;2&lt;/b&gt;, warrant further investigation for therapeutic applications. This study highlights the potential of endophytic actinomycetes from &lt;i&gt;Aloe vera&lt;/i&gt; as a valuable resource for drug discovery.

Reactive oxygen species (ROS), a class of highly reactive molecules, are closely linked to the pathogenesis of various cancers. While ROS primarily originate from normal cellular processes, external stimuli can also contribute to their production. Cancer cells typically exhibit elevated ROS levels due to disrupted redox homeostasis, characterized by an imbalance between antioxidant and oxidant species. ROS play a dual role in cancer biology: at moderate levels, they facilitate tumor progression by regulating oncogenes and tumor suppressor genes, inducing mutations, promoting proliferation, extracellular matrix remodeling, invasion, immune modulation, and angiogenesis. However, excessive ROS levels can cause cellular damage and initiate apoptosis, necroptosis, or ferroptosis.

Hand‑foot syndrome (HFS) is defined as a major adverse reaction to capecitabine; however, the underlying mechanisms remain unclear. In total, 85 patients who were taking oral capecitabine were included in the present study and these patients were divided into HFS‑positive and HFS‑negative groups. Serum samples were collected from patients and an untargeted metabolomics analysis was conducted using ultra‑high performance liquid chromatography‑mass spectrometry/mass spectrometry. The present study aimed to investigate the presence of metabolites in the serum of patients that developed HFS in response to capecitabine treatment. A total of 193 differential metabolites were identified, with 134 upregulated and 59 downregulated. Bioinformatics analysis revealed four novel metabolites that may be associated with HFS. Subsequent in vitro experiments were conducted to explore the damaging effects of capecitabine and its associated metabolites on human adult keratinocyte cell line, TPA‑treated (HaCaT) cells. Results of the present study revealed that aciclovir and lamivudine affected cellular damage at the highest level. In conclusion, the present study aimed to systematically and comprehensively describe the metabolites present in patients with capecitabine‑induced HFS and may further the current understanding of the capecitabine pathways that play a key role in HFS.

Mefenamic acid (MA) represents an efficient nonsteroidal anti-inflammatory drug (NSAID) for treatment in many circumstances of painful conditions and inflammation, but its poor water solubility and gastrointestinal side effects often obstruct its clinical application. Consequently, researchers have been conducting studies on the synthesis of prodrugs and heterocyclic compounds as MA derivatives for the improvement of their pharmacological profile. This review discusses an overview of recent developments in the synthesis and biological applications of MA derivatives. It covers several strategies used to modify the chemical structure of MA to pursue pharmacokinetic improvement, solubility, and targeting features, among which are heterocyclic moieties and prodrug design. Following the many synthetically produced derivatives of MA, mainly proposed between classic organic synthesis and more recent methodologies, such as microwave-assisted synthesis and green chemistry protocols, this review will consider how different structural variations are able to influence the assumed pharmacological actions: analgesic, anti-inflammatory, and anticancer. The findings demonstrate significant progress toward the development of safer and more effective NSAID therapies; thus, they support, in a broad and unprecedented way, the potential of MA derivatives and prodrugs in transforming the state of pain management and inflammation treatment.

Many studies have focused on adverse reactions caused by platinum drugs but neglected subsequent toxicities and the mechanisms during patient recovery after chemotherapy with different platinum drugs, which need attention because of the heavy metal platinum.

This study investigates the antitumor and immunomodulatory effects of compound aluminum sulfate (CAS) solution in murine melanoma models. Using syngeneic B16-F10 and B16-OVA tumor models, we demonstrate that intratumoral CAS injection significantly inhibits primary tumor growth and lung metastasis. Flow cytometry analysis reveals that CAS treatment increases splenic populations of CD3+CD8+ cytotoxic T cells, CD3+CD44+ memory T cells, and NK cells, while enhancing CD8+ T cell infiltration in tumor tissue. ELISA results show elevated levels of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-2) in splenic culture supernatants and serum following CAS administration. Immunofluorescence staining confirms increased expression of CD8 and IFN-γ proteins in tumor tissues of CAS-treated mice. Results indicate that CAS exerts its antitumor effects through direct cytotoxicity and by modulating both systemic and local immune responses. The dual action of CAS, which combines tumor necrosis with immunostimulation, positions it as a promising therapeutic agent for cancer treatment. This study offers valuable insights into the mechanisms underlying CAS's action and underscores its potential clinical applications in oncology.

We designed and synthesised 22 new urolithin derivatives (UDs) based on methyl-urolithin A (mUA) to identify anti-cancer drugs with high efficacy and low toxicity and evaluated their anti-cancer activities in vitro. Cytotoxicity tests were performed on three cell lines (DU145, T24, and HepG2) and a human normal cell line (HK-2). The half-inhibitory concentration (IC50) of derivative UD-4c to hepatoma HepG2 cells (IC50 = 4.66 ± 0.12 μM) was significantly lower than that of sorafenib (IC50 =7.76 ± 0.12 μM), and exhibited less toxicity to HK-2 cells. Preliminary studies on the mechanism revealed that the derivative UD-4c could significantly inhibit the HepG2 cell growth and colony formation, block the HepG2 cell cycle in the G2/M phase, and induce apoptosis of HepG2 cells dose-dependently. The derivative UD-4c can be used as a potential lead compound to further develop new drugs for hepatocellular carcinoma treatment based on the evaluation of anti-cancer activity.

Hypertension is documented in dogs with cancer receiving toceranib, but no studies have evaluated left ventricular (LV) systolic function and biomarkers of endothelial function.

The centrosome, a vital component in mitosis in eukaryotes, plays a pivotal role in cancer progression by influencing the proliferation and differentiation of malignant cells, making it a significant therapeutic target. We collected genes associated with centrosomes from existing literature and established a prognostic model for 85 osteosarcoma patients from the TARGET database. Genes associated with prognosis were identified through univariate Cox regression. We then mitigated overfitting by addressing collinearity using LASSO regression. Ultimately, a set of five genes was selected for the model through multivariable Cox regression. Model performance was assessed using ROC curves, which yielded a training set AUC of 0.965 and a validation set AUC of 0.770, indicating satisfactory model performance. We further identified genes with differential expression in high and low-risk groups and conducted functional enrichment analysis using KEGG, GO, Progeny, GSVA, and GSEA. Results revealed significant variances in various immune-related pathways between high and low-risk cohorts. Analysis of the immune microenvironment using ssGSEA and ESTIMATE indicated that individuals with unfavorable prognoses had lower immune scores, stromal scores, and ESTIMATE scores, coupled with higher tumor purity. This suggests that high-risk individuals have compromised immune microenvironments, potentially contributing to their unfavorable prognoses. Additionally, drug sensitivity and molecular docking analysis revealed increased responsiveness to paclitaxel in high-risk individuals, implying its prognostic value. The JTB-encoded protein exhibited a negative binding energy of - 5.5 kcal/mol when interacting with paclitaxel, indicating its potential to enhance the patient's immune microenvironment. This framework enables patient prognosis prediction and sheds light on paclitaxel's mechanism in osteosarcoma treatment, facilitating personalized treatment approaches.

Bacteria such as Vibrio spp. in the marine environment can produce secondary metabolites which have significant potential applications in pharmaceuticals. In a study to discover bioactive secondary metabolites from marine Vibrio spp., the strain DJA11 was encountered. HPLC/UV-guided isolation of the crude extract from this strain has led to the discovery of compound 1. Prostate cancer (PCa) is one of the biggest worldwide health issues because of its high diagnosis. CWR22Rv1 (22Rv1) is mutated in WT p53 and AR, C4-2 is derived from androgen-dependent human LNCaP and PC-3 is an androgen-independent cancer cell type. It was found that compound 1 exhibited no significant cytotoxicity at concentrations below 50 μM to human PCa cells, including 22Rv1, C4-2, and PC-3, like normal cell HEK293T. In addition, we presented that 1 inhibited the invasiveness and proliferation of 22Rv1, PC-3, and C4-2 cells by suppressing the activation of p-AKT, p-mTOR, p-STAT3, HSP90, and HSP70. Moreover, treatment with 1 decreased the mRNA expression level of ErbB4, PDK1, STAT3, HSP70, and HSP90 in some PCa cells. Therefore, compound 1 may have therapeutic potential in PCa due to its role in suppressing cancer proliferation and metastasis.

Gastric cancer is a significant global health issue. Celastrol, a natural compound, has shown antitumor potential, but its molecular mechanism in gastric cancer remains unclear. In this study, we treated HGC-27 cells with celastrol and employed CCK8, colony formation, and Transwell assays, revealing its inhibitory effect on cell proliferation and migration. Flow cytometry assay results showed that celastrol could elevate the level of reactive oxygen species (ROS) in HGC-27 cells. By using the iron ion and malondialdehyde (MDA) detection kits, it was found that celastrol promoted the accumulation of iron ions (Fe[Formula: see text] in HGC-27 cells, increased the MDA content, and simultaneously decreased the glutathione (GSH) content. Additionally, Western blot analysis indicated that celastrol exerts an inhibitory effect on the expression of ferroptosis-marker proteins GPX4 and SLC7A11. PCR array and further experiments identified CERKL as a key factor, whose downregulation by celastrol was associated with enhanced ferroptosis. In vivo, celastrol inhibited tumor growth without affecting body weight or organ histology. Our findings suggest that celastrol may inhibit gastric cancer via CERKL-regulated ferroptosis, providing a potential therapeutic strategy.

Biological systems do not exist in isolation. Analogous to the intricate design of a spider web, the metabolic adaptations propagated by glioblastoma cells are interlaced, creating a "defense mechanism" that increases the likelihood of mutagenesis and proliferation, while mitigating stress-induced tumor cell death and immune evasion. Previous studies have observed the role of cardiolipin (CL) in the electron transport chain (ETC) function and several other intracellular signaling pathways. Our review provides a synopsis of the existing knowledge about CL in glioblastoma and its complex relationship with metabolic reprogramming at the subcellular level. Through a meticulous examination of CL defects due to its biogenesis and stress-induced modifications, we seek to elucidate the multifaceted connections between aberrant CL variants and the metabolic alterations that underlie glioblastoma progression. A comprehensive grasp of these mechanisms could provide future direction in designing chemotherapeutic agents that selectively target glioblastoma, are less harmful to normal cells, and therefore, may extend patient survival.

Flow cytometry is a powerful technique used in biology and medicine to analyze and quantify characteristics of individual cells in a heterogeneous population. It provides information about various cellular properties, such as size, complexity, surface markers, and internal components. We developed a flow cytometry-based method for the analysis of drug-induced topoisomerase II cleavage complex (Top2cc). This method allows a rapid analysis of a high number of cells in their cell cycle phase context. Moreover, it can be applied to almost any human cell type, including clinical samples. The methodology is valuable for conducting high-throughput analyses of drugs that target Top2, enabling the discrimination of the specific isoform affected, and tracking its removal. Since drug-stabilized Top2cc may interfere with several nuclear processes of DNA, this method allows the study of different pathways that may be hampered, evaluating their impact under different cellular conditions.

Topoisomerases unlink chromosomes and relieve topological stress. Topoisomerase "poisons" are widely used chemotherapeutics that stabilize topoisomerase complexes on DNA, leading to cytotoxic DNA breaks and cancer cell killing. It is well established that topoisomerase poisons interfere with DNA replication, which is thought to be a major physiological target of these drugs. However, many questions remain about the mechanisms by which topoisomerase poisons impact DNA replication and the downstream consequences. Here, we describe assays to study topoisomerase poisons during vertebrate DNA replication using Xenopus egg extracts. These approaches allow for replication intermediates formed following poison treatment to be carefully monitored with high temporal resolution.