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Micromachines Jun 2024This study focuses on the development and compressive characteristics of magnetorheological elastomeric foam (MREF) as an adaptive cushioning material designed to...
This study focuses on the development and compressive characteristics of magnetorheological elastomeric foam (MREF) as an adaptive cushioning material designed to protect payloads from a broader spectrum of impact loads. The MREF exhibits softness and flexibility under light compressive loads and low strains, yet it becomes rigid in response to higher impact loads and elevated strains. The synthesis of MREF involved suspending micron-sized carbonyl Fe particles in an uncured silicone elastomeric foam. A catalyzed addition crosslinking reaction, facilitated by platinum compounds, was employed to create the rapidly setting silicone foam at room temperature, simplifying the synthesis process. Isotropic MREF samples with varying Fe particle volume fractions (0%, 2.5%, 5%, 7.5%, and 10%) were prepared to assess the effect of particle concentrations. Quasi-static and dynamic compressive stress tests on the MREF samples placed between two multipole flexible strip magnets were conducted using an Instron servo-hydraulic test machine. The tests provided measurements of magnetic field-sensitive compressive properties, including compression stress, energy absorption capability, complex modulus, and equivalent viscous damping. Furthermore, the experimental investigation also explored the influence of magnet placement directions (0° and 90°) on the compressive properties of the MREFs.
PubMed: 38930752
DOI: 10.3390/mi15060782 -
Micromachines Jun 2024In this work, we present a compact, bifunctional chip-based sensor setup that measures the temperature and electrical conductivity of water samples, including specimens...
In this work, we present a compact, bifunctional chip-based sensor setup that measures the temperature and electrical conductivity of water samples, including specimens from rivers and channels, aquaculture, and the Atlantic Ocean. For conductivity measurements, we utilize the impedance amplitude recorded via interdigitated electrode structures at a single triggering frequency. The results are well in line with data obtained using a calibrated reference instrument. The new setup holds for conductivity values spanning almost two orders of magnitude (river versus ocean water) without the need for equivalent circuit modelling. Temperature measurements were performed in four-point geometry with an on-chip platinum RTD (resistance temperature detector) in the temperature range between 2 °C and 40 °C, showing no hysteresis effects between warming and cooling cycles. Although the meander was not shielded against the liquid, the temperature calibration provided equivalent results to low conductive Milli-Q and highly conductive ocean water. The sensor is therefore suitable for inline and online monitoring purposes in recirculating aquaculture systems.
PubMed: 38930725
DOI: 10.3390/mi15060755 -
Medicina (Kaunas, Lithuania) Jun 2024Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid...
Platinum-based combination chemotherapy, including cisplatin and carboplatin, are important cytotoxic anti-cancer agents that are widely used to treat various solid tumors. Carboplatin has a similar effect on survival in small cell lung cancer, but generally has a milder toxicity profile when compared with cisplatin. Both may cause moderate or severe neurotoxicity, but ocular neurotoxicity from carboplatin is rarely reported. A 79-year-old man underwent intravenous polychemotherapy (atezolizumab, etoposide, and carboplatin) for small cell lung cancer. One week after the second cycle of chemotherapy, he reported bilateral visual loss as hand motion in both eyes. Dilated fundus examination showed retinal arterial narrowing without hemorrhage, and diffuse choroidal and retinal thinning was observed in an optical coherence tomography scan. Fluorescein angiography revealed significantly delayed circulation without evidence of obstructive lesions. 30-Flicker electroretinogram testing showed a complete absence of cone response in both eyes. The patient's visual acuity aggravated to no light perception in both eyes, even after the cessation of chemotherapy. Carboplatin combination chemotherapy administered at therapeutic doses can result in irreversible visual loss, a side effect that is not widely acknowledged. When using carboplatin, physicians should be aware of its potential ocular toxicity.
Topics: Humans; Carboplatin; Male; Aged; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Combined Chemotherapy Protocols; Vision Disorders; Antineoplastic Agents
PubMed: 38929609
DOI: 10.3390/medicina60060992 -
Antioxidants (Basel, Switzerland) Jun 2024PAPLAL, a mixture of platinum (nPt) and palladium (nPd) nanoparticles, is widely used as a topical agent because of its strong antioxidant activity. Allergic contact...
PAPLAL, a mixture of platinum (nPt) and palladium (nPd) nanoparticles, is widely used as a topical agent because of its strong antioxidant activity. Allergic contact dermatitis (ACD) is one of the most common occupational skin diseases worldwide. However, the role of oxidative stress in ACD remains unclear. In the present study, we investigated the protective effects of topical PAPLAL treatment on 2,4-dinitrofluorobenzene (DNFB)-induced ACD. DNFB treatment increased 8-isoprostane content; upregulated , , and , pro-oxidant genes; and downregulated , an antioxidant gene, indicating oxidative damage in the ear skin. PAPLAL therapy significantly reduced ear thickness associated with the downregulation of inflammatory cytokine-related genes. PAPLAL also significantly increased the expression of the stress-response-related genes and as well as their target genes, but failed to alter the expression of redox-related genes. Furthermore, loss worsened ACD pathologies in the ear. These results strongly suggest that PAPLAL protects against ACD through its antioxidant activity and activation of the AHR and NRF2 axes. The antioxidant PAPLAL can be used as a novel topical therapy for ACD that targets oxidative stress.
PubMed: 38929186
DOI: 10.3390/antiox13060748 -
International Journal of Molecular... Jun 2024Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach...
Higher EpCAM-Positive Extracellular Vesicle Concentration in Ascites Is Associated with Shorter Progression-Free Survival of Patients with Advanced High-Grade Serous Carcinoma.
Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance.
Topics: Humans; Epithelial Cell Adhesion Molecule; Extracellular Vesicles; Female; Ascites; Middle Aged; Aged; Biomarkers, Tumor; Progression-Free Survival; Cystadenocarcinoma, Serous; Ovarian Neoplasms; Prognosis; Adult; Neoplasm Grading
PubMed: 38928484
DOI: 10.3390/ijms25126780 -
International Journal of Molecular... Jun 2024The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids,... (Review)
Review
The peripheral nervous system can encounter alterations due to exposure to some of the most commonly used anticancer drugs (platinum drugs, taxanes, vinca alkaloids, proteasome inhibitors, thalidomide), the so-called chemotherapy-induced peripheral neurotoxicity (CIPN). CIPN can be long-lasting or even permanent, and it is detrimental for the quality of life of cancer survivors, being associated with persistent disturbances such as sensory loss and neuropathic pain at limb extremities due to a mostly sensory axonal polyneuropathy/neuronopathy. In the state of the art, there is no efficacious preventive/curative treatment for this condition. Among the reasons for this unmet clinical and scientific need, there is an uncomplete knowledge of the pathogenetic mechanisms. Ion channels and transporters are pivotal elements in both the central and peripheral nervous system, and there is a growing body of literature suggesting that they might play a role in CIPN development. In this review, we first describe the biophysical properties of these targets and then report existing data for the involvement of ion channels and transporters in CIPN, thus paving the way for new approaches/druggable targets to cure and/or prevent CIPN.
Topics: Humans; Antineoplastic Agents; Peripheral Nervous System Diseases; Ion Channels; Animals; Neurotoxicity Syndromes; Membrane Transport Proteins; Neoplasms
PubMed: 38928257
DOI: 10.3390/ijms25126552 -
International Journal of Molecular... Jun 2024Monofunctional platinum complexes offer a promising alternative to cisplatin in cancer chemotherapy, showing a unique mechanism of action. Their ability to induce minor...
Monofunctional platinum complexes offer a promising alternative to cisplatin in cancer chemotherapy, showing a unique mechanism of action. Their ability to induce minor helix distortions effectively inhibits DNA transcription. In our study, we synthesized and characterized three monofunctional Pt(II) complexes with the general formula [Pt(en)(L)Cl]NO, where en = ethylenediamine, and L = pyridine (py), 2-methylpyridine (2-mepy), and 2-phenylpyridine (2-phpy). The hydrolysis rates of [Pt(en)(py)Cl]NO () and [Pt(en)(2-mepy)Cl]NO () decrease with the bulkiness of the auxiliary ligand with k() = 2.28 ± 0.15 × 10 s and k() = 8.69 ± 0.98 × 10 s at 298 K. The complex [Pt(en)(2-phpy)Cl]Cl () demonstrated distinct behavior. Upon hydrolysis, an equilibrium (K = 0.385 mM) between the complexes [Pt(en)(2-phpy)Cl] and [Pt(en)(2-phpy-H)] was observed with no evidence (NMR or HR-ESI-MS) for the presence of the aquated complex [Pt(en)(2-phpy)(HO)]. Despite the kinetic similarities between phenanthriplatin and (), complexes () and () exhibit minimal activity against A549 lung cancer cell line (IC > 100 μΜ), whereas complex () exhibits notable cytotoxicity (IC = 41.11 ± 2.1 μΜ). In examining the DNA binding of () and () to the DNA model guanosine (guo), we validated their binding through guoN7, which led to an increased population of the C3'- sugar conformation, as expected. However, we observed that the rapid transition E (C2') ↔ E (C3'), in the case of [Pt(en)(py)(guo)](NO) ([-guo]), slows down in the case of [Pt(en)(2-mepy)(guo)](NO) ([-guo]), resulting in separate signals for the two conformers in the H NMR spectra. This phenomenon arises from the steric hindrance between the methyl group of pyridine and the sugar moiety of guanosine. Notably, this hindrance is absent in [-(9-MeG)] (9-MeG = 9-methylguanine), probably due to the absence of a bulky sugar unit in 9-MeG. In the case of (), where the bulkiness of the substitution on the pyridine is further increased by a phenyl group, we observed a notable proximity between 9-MeGH8 and the phenyl ring of 2-phpy. Considering that only () exhibited good cytotoxicity against the A549 cancer cell line, it is suggested that auxiliary ligands, L, with an extended aromatic system and proper orientation in complexes of the type cis-[Pt(en)(L)Cl]NO, may enhance the cytotoxic activity of such complexes.
Topics: Antineoplastic Agents; DNA; Humans; Ligands; Organoplatinum Compounds; Cell Line, Tumor; Hydrolysis; Platinum; A549 Cells
PubMed: 38928230
DOI: 10.3390/ijms25126526 -
Cancers Jun 2024Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M...
Lazertinib versus Platinum-Based Chemotherapy with Epidermal Growth Factor Receptor (EGFR)-Positive Non-Small-Cell Lung Cancer after Failing EGFR-Tyrosine Kinase Inhibitor: A Real-World External Comparator Study.
BACKGROUND
Lazertinib is a third-generation tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR-TKI) that selectively inhibit common EGFR mutation and T790M mutation in non-small-cell lung cancer (NSCLC) patients. No previous studies have compared lazertinib to platinum-based chemotherapy. We have compared lazertinib with platinum-based chemotherapy in EGFR-mutated NSCLC patients after previous EGFR-TKI therapy.
METHODS
We retrospectively compared 200 patients from LASER201, LASER301, and LASER-PMS studies to 334 patients who were treated with platinum-based chemotherapy after previous EGFR-TKI from the Samsung Medical Center. After propensity score matching (PSM), we selected 156 patients from each group. The primary outcome was progression-free survival (PFS), with overall survival (OS), objective response rate (ORR), and time to treatment discontinuation (TTD) as secondary outcomes.
RESULTS
The median follow-up of PFS was 15.61 months in the lazertinib group and 21.67 months in the external control group. The PFS was significantly longer in patients who were treated with lazertinib than those treated with platinum-based chemotherapy (10.97 months vs. 5.10 months; adjusted hazard ratio (HR) 0.40; 95% confidence interval (CI), 0.29-0.55; < 0.01) after PSM. Lazertinib showed superior OS (32.23 months vs. 18.73 months; adjusted HR 0.45; 95% CI, 0.29-0.69; < 0.001), ORR (64.1% vs. 47.4%), and TTD (11.66 months vs. 6.73 months; adjusted HR 0.54; 95% CI, 0.39-0.75; < 0.001) compared to platinum-based chemotherapy.
CONCLUSION
Based on this retrospective, external control study, lazertinib has demonstrated significantly better efficacy compared with platinum-based chemotherapy. The external controls provide important context to evaluate efficacy in single-arm studies.
PubMed: 38927875
DOI: 10.3390/cancers16122169 -
Bioengineering (Basel, Switzerland) Jun 2024(1) Background: Medical devices, especially neuromodulation devices, are often explanted for a variety of reasons. The removal process imparts significant forces on...
(1) Background: Medical devices, especially neuromodulation devices, are often explanted for a variety of reasons. The removal process imparts significant forces on these devices, which may result in device fracture and tissue trauma. We hypothesized that a device's form factor interfacing with tissue is a major driver of the force required to remove a device, and we isolated helical and linear electrode structures as a means to study atraumatic removal. (2) Methods: Ductile linear and helical microwire structure electrodes were fabricated from either Gold (Au) or Platinum-Iridium (Pt-Ir, 90-10). Removal forces were captured from synthetic gel models and following chronic implantation in rodent and porcine models. Devices were fully implanted in the animal models, requiring a small incision (<10 mm) and removal via tissue forceps. (3) Results: Helical devices were shown to result in significantly lower maximal removal forces in both synthetic gel and rodent studies compared to their linear counterparts. Chronically (1 yr.), the maximal removal force of helical devices remained under 7.30 N, for which the Platinum-Iridium device's tensile failure force was 32.90 ± 2.09 N, resulting in a safety factor of 4.50. (4) Conclusions: An open-core helical structure that can freely elongate was shown to result in reduced removal forces both acutely and chronically.
PubMed: 38927847
DOI: 10.3390/bioengineering11060611 -
Genes May 2024Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and... (Review)
Review
Small cell lung cancer (SCLC) is an aggressive neuroendocrine carcinoma accounting for 15% of lung cancers with dismal survival outcomes. Minimal changes in therapy and prognosis have occurred in SCLC for the past four decades. Recent progress in the treatment of extensive-stage disease (ES-SCLC) has been marked by incorporating immune checkpoint inhibitors (ICIs) into platinum-based chemotherapy, leading to modest improvements. Moreover, few second-line-and-beyond treatment options are currently available. The main limitation for the molecular study of SCLC has been the scarcity of samples, because only very early diseases are treated with surgery and biopsies are not performed when the disease progresses. Despite all these difficulties, in recent years we have come to understand that SCLC is not a homogeneous disease. At the molecular level, in addition to the universal loss of retinoblastoma (RB) and TP53 genes, a recent large molecular study has identified other mutations that could serve as targets for therapy development or patient selection. In recent years, there has also been the identification of new genetic subtypes which have shown us how intertumor heterogeneity exists. Moreover, SCLC can also develop intratumoral heterogeneity linked mainly to the concept of cellular plasticity, mostly due to the development of resistance to therapies. The aim of this review is to quickly present the current standard of care of ES-SCLC, to focus on the molecular landscapes and subtypes of SCLC, subsequently present the most promising therapeutic strategies under investigation, and finally recap the future directions of ongoing clinical trials for this aggressive disease which still remains a challenge.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Immune Checkpoint Inhibitors; Mutation
PubMed: 38927637
DOI: 10.3390/genes15060701