A novel and robust electrochemical sensing tool for the determination of vismodegib (VIS), an anticancer drug, has been developed by integrating the selective recognition capabilities of molecularly imprinted polymer (MIP) and the sensitivity enhancement capability of metal-organic framework (MOF). Prior to this step, the electrochemical behavior of VIS was investigated using a bare glassy carbon electrode (GCE). It was observed that in 0.5 M H2SO4 solution as electrolyte, VIS has an oxidation peak around 1.3 V and the oxidation mechanism is diffusion controlled. The determination of VIS in a standard solution using a bare GCE showed a linear response in the concentration range from 2.5 μM to 100 μM, with a limit of detection (LOD) of 0.75 μM. Since sufficient sensitivity and selectivity could not be achieved with bare GCE, a MIP sensor was developed in the next step of the study. For this purpose, the GCE surface was first modified by drop casting with as-synthesized Co-MOF. Subsequently, a MIP network was synthesized via a thermal polymerization approach using 2-acrylamido-2-methylpropanesulfonic acid (AMPS) as monomer and VIS as template. MOFs are ideal electrode materials due to their controllable and diverse morphologies and modifiable surface properties. These characteristics enable the development of MIPs with more homogeneous binding sites and high affinity for target molecules. Integrating MOFs could help the performance of sensors with the desired stability and reproducibility. Electrochemical analysis revealed an observable enhancement of the output signal by the incorporation of MOF molecules, which is consistent with the sensitivity-enhancing role of MOF by providing more anchoring sites for the attachment of the polymer texture to the electrode surface. This MOF-MIP sensor exhibited impressive linear dynamic ranges ranging from 0.1 to 1.0 pM for VIS, with detection limits in the low picomolar range. In addition, the MOF-MIP sensor offers high accuracy, selectivity and precision for the determination of VIS, with no interference observed from complex media of serum samples. Additionally, in this study, Analytical GREEnness metric (AGREE), Analytical GREEnness preparation (AGREEprep) and Blue Applicability Grade Index (BAGI) were used to calculate the green profile score.

Aclarubicin (aclacinomycin A) is one of the anthracycline antineoplastic antibiotics with a multifaceted mechanism of antitumor activity. As a second-generation drug, it offers several advantages compared to standard anthracycline drugs such as doxorubicin or daunorubicin, which could position it as a potential blockbuster drug in antitumor therapy. Key mechanisms of action for aclarubicin include the inhibition of both types of topoisomerases, suppression of tumor invasion processes, generation of reactive oxygen species, inhibition of chymotrypsin-like activity, influence on cisplatin degradation, and inhibition of angiogenesis. Therefore, aclarubicin appears to be an ideal candidate for antitumor therapy. However, despite initial interest in its clinical applications, only a limited number of high-quality trials have been conducted thus far. Aclarubicin has primarily been evaluated as an induction therapy in acute myeloid and lymphoblastic leukemia. Studies have indicated that aclarubicin may hold significant promise for combination therapies with other anticancer drugs, although further research is needed to confirm its potential. This paper provides an in-depth exploration of aclarubicin\'s diverse mechanisms of action, its pharmacokinetics, potential toxicity, and the clinical trials in which it has been investigated.

Chemotherapy is a common and effective treatment for cancer, but these drugs are also associated with significant side effects affecting patients\' well-being. One such debilitating side effect is mucositis, characterized by inflammation, ulcerations, and altered physiological functions of the gastrointestinal (GI) tract\'s mucosal lining. Understanding the mechanisms of chemotherapy-induced intestinal mucositis (CIM) is crucial for developing effective preventive measures and supportive care. Chemotherapeutics not only target cancer cells but also rapidly dividing cells in the GI tract. These drugs disrupt endoplasmic reticulum (ER) homeostasis, leading to ER-stress and activation of the unfolded protein response (UPR) in various intestinal epithelial cell types. The UPR triggers signaling pathways that exacerbate tissue inflammation and damage, influence the differentiation and fate of intestinal epithelial cells, and compromise the integrity of the intestinal mucosal barrier. These factors contribute significantly to mucositis development and progression. In this review, we aim to give an in-depth overview of the role of ER-stress in mucositis and its impact on GI function. This will provide valuable insights into the underlying mechanisms and highlighting potential therapeutic interventions that could improve treatment-outcomes and the quality of life of cancer patients.

Resulted from the severe side effects, the development of inexpensive, simple and sensitive method for amethopterin (ATP, an antineoplastic drug) is very important but it still remains a challenge. In this work, low cost nanohybrid composed of carbon nanobowl (CNB) and β-cyclodextrins (β-CD) (CNB-CD) was prepared with a simple autopolymerization way and applied as electrode material to develop a novel electrochemical sensor of ATP. Scanning-/transmission-electron microscopy, Fourier transform infrared spectrum, photographic image and electrochemical technologies were utilized to characterize morphologies and structure of the as-prepared CNB and CNB-CD materials. On the basic of the coordination advantages from CNB (prominent electrical property and surface area) and β-CD (superior molecule-recognition and solubility capabilities), the CNB-CD nanohybrid modified electrode exhibits superior sensing performances toward ATP, and a low detection limit of 0.002 μM coupled with larger linearity of 0.005-12.0 μM are obtained. In addition, the as-prepared sensor offers desirable repeatability, stability, selectivity and practical application property, confirming that this proposal may have important applications in the determination of ATP.

OBJECTIVE: Pulmonary fibrosis (PF) is a severe, progressive disease, which may be caused by exposure to certain medications.
METHODS: We queried the U.S. FDA Adverse Event Reporting System (FAERS) from 2000 to 2022, using the search terms \"pulmonary fibrosis\" and \"idiopathic pulmonary fibrosis\" and excluded reports with patients under the age of 18 years, and patients with unknown sex or age. Reports were sorted by generic drug names, counted, and plotted over time using a best-fit trendline based on an exponential function.
RESULTS: From 2000 to 2022, there were 24 095 935 adverse drug events reported in FAERS, of which 17 520 (0.07%) were reported as PF. After excluding reports containing patients with unknown age (5255, 30%), sex (122, 0.7%), and age below 18 years old (155, 0.9%), our study included 11 988 reports. The mean age of the study sample was 66.5 ± 13.1 years, and 6248 patients (52.1%) were male. Plotting the 11 988 reports by year revealed an exponential best fit line (R2 = 0.88) with a positive slope over time. The top five drug classes associated with PF were disease modifying antirheumatic drugs (DMARDs, 39.4%), antineoplastic agents (26.4%), cardiovascular agents (12.6%), corticosteroids (4.6%), and immunosuppressive agents (4.0%).
CONCLUSIONS: A 23-year analysis of the FAERS database revealed exponentially increasing adverse event reports of PF. Significant annual increases in reporting of PF suspected with DMARDs and antineoplastic agents were identified. Our study highlights important trends, which should be used to guide PF research related to drugs of potential importance.

Internal contamination of healthcare professionals by antineoplastic drugs (ADs) remains a current occupational health issue, particularly because these compounds are classified as dangerous to handle by the NIOSH. In order to improve preventive actions, a study of the factors associated with this internal contamination was conducted among nursing staff in health care institutions. This study is a statistical analysis of metadata from a cross-sectional observational study conducted among nurses in two French hospitals. The internal contamination of each nurse was assessed in a previous study and was defined by whether or not at least one studied AD was detected in at least one urine sample. Three urine samples and a self-questionnaire were collected for each participant. Analysis of five ADs (cyclophosphamide, ifosfamide, metabolite of 5-fluorouracil, methotrexate, doxorubicin) were performed by liquid chromatography coupled to tandem mass spectrometry. A multivariate stepwise descending regression model was used to determine factors associated with internal contamination by coupling data from a self-questionnaire with internal contamination data. A total of 74 nurses participated to the study and 68 were included for this work: 39 nurses with and 29 without detectable internal ADs contamination. Two protective factors of internal contamination could be identified: a high \"glove wearing score\" (OR: 0.957; 95%CI: 0.93-0.98; p < 0.01) and a high \"total number of years handling ADs and/or caring for patients treated with ADs\" (OR: 0.797; 95%CI: 0.67-0.91; p < 0.01). In addition, three factors contributing to internal contamination were identified, namely \"feeling sufficiently informed about tasks exposing to ADs\" (OR: 9.585; 95%CI: 2.23-57.05; p < 0.01), \"disposal of a waste bin containing equipment used for administration of the ADs studied\" (OR: 8.04; 95%CI: 1.87-46.08; p < 0.01) and \"changing sheets and/or making bed of a patient treated by one of the ADs studied\" (OR: 10.479; 95%CI: 1.43-133.30; p < 0.05). Thus, the use of gloves when handling ADs directly or indirectly and the contaminating nature of certain tasks should be taken into account when (1) implementing preventive actions in health care services and (2) training and informing exposed staff. Further studies would be desirable to confirm these results and extend them to other professional categories.

The inorganic antineoplastic drug cisplatin was made to react in solution with the dipeptide cysteinylglycine (CysGly), chosen as a functional model of glutathione, and the reaction products were analyzed using electrospray ionization mass spectrometry (ESI-MS). Selected complexes, i.e., the primary substitution product cis-[PtCl(NH3)2(CysGly)]+ and the chelate cis-[PtCl(NH3)(CysGly)]+, were submitted to IR multiple photon dissociation (IRMPD) spectroscopy obtaining their vibrational features. The experimental IR ion spectra were compared with the calculated IR absorptions of different plausible isomeric families, finding CysGly to bind preferentially platinum(II) via its deprotonated thiolic group in the monovalent complex, cis-[PtCl(NH3)2(CysGly)]+, and to evolve in the S,N-bound chelate structure cis-[PtCl(NH3)(CysGly)]+ through the SH and NH2 functionality of the cysteine residue. Moreover, our findings indicate that the platination reaction does not affect the CysGly peptide bond, which remains in its trans configuration. These results provide additional insights into the reactivity of Pt(II)-complexes with glutathione which is involved in cellular cisplatin resistance.

The occupational exposure of caregivers to antineoplastic agents has been demonstrated since 1979. Since the early 1990s, numerous studies from several countries have demonstrated the contamination of care facilities by antineoplastic drugs. As it is easier to sample, most contamination measurements in workers are carried out in urine sample. The distribution and elimination half-lives of irinotecan suggest that blood can be considered as better than urine for the biomonitoring of a potential contamination of healthcare workers. We describe here the development and the validation of a UHPLC-MS/MS method to simultaneously quantify irinotecan, and two of its main metabolites, APC and SN-38, at ultra-trace levels in plasma and red blood cells (RBC). This method has been applied to blood samples collected from several healthcare services in a French comprehensive cancer center. The results demonstrate that the method is sensitive enough to identify a contamination of healthcare workers by irinotecan and SN-38 at very low concentrations. Moreover, the results show that analysis of RBC is of great interest and complementary to that of serum.

To determine whether the blood-brain barrier (BBB) opens to enhance drug delivery during the acute stage of unsaturated fat embolism.
We infused oleic, linoleic, and linolenic acid emulsions through the right common carotid artery of rats, followed by trypan blue for gross and lanthanum for electron microscopic (EM) examination. Doxorubicin and temozolomide were also administered, and then the rats were euthanized at 30 min, 1 h, and 2 h. Trypan blue hue was analyzed to semiquantitatively measure BBB opening. Desorption electrospray ionization-mass spectrometry (DESI-MS) imaging was used to evaluate drug delivery.
Trypan blue staining observed in each group 30 min after emulsion infusion increased at 1 h and decreased after 2 h in the oleic acid group. The linoleic and linolenic acid groups showed weak staining over time. The hue and trypan blue analysis results were corroborative. EM showed tight junction opening, whereas DESI-MS imaging showed increased doxorubicin and temozolomide signal intensities in ipsilateral hemispheres of all three groups.
We demonstrated that oleic, linoleic, and linolenic acid emulsions opened the BBB, promoting drug delivery to the brain. Hue analysis and DESI-MS imaging are appropriate for analysis of doxorubicin and temozolomide concentrations in brain tissue.

With increasing numbers of cancer cases, the use of antineoplastic agents is expected to rise. This will be accompanied by an increase in occupational exposure, which can cause unwanted health effects in workers. Our aim was to give an overview of genotoxic and epigenetic effects after occupational exposure to antineoplastic agents and to assess the concentration-effect relation. Four databases were searched for papers investigating genotoxic and/or epigenetic effects of occupational exposure to antineoplastic agents. Out of the 245 retrieved papers, 62 were included in this review. In this systematic literature review, we confirmed that exposure of healthcare workers to antineoplastic agents can lead to genotoxic damage. However, we observed a lack of data on exposure as well as genotoxic and epigenetic effects in workers other than healthcare workers. Furthermore, gaps in the current knowledge regarding the potential epigenetic effects caused by antineoplastic drug exposure and regarding the link between internal antineoplastic drug concentration and genotoxic and epigenetic effects after occupational exposure to antineoplastic agents were identified, offering a first step for future research.