Spatial confinement: An effective strategy to improve H2O and SO2 resistance of the expandable graphite-modified TiO2-supported Pt nanocatalysts for CO oxidation.

The expandable graphite (EG) modified TiO2 nanocomposites were prepared by the high shear method using the TiO2 nanoparticles (NPs) and EG as precursors, in which the amount of EG doped in TiO2 was 10 wt.%. Followed by the impregnation method, adjusting the pH of the solution to 10, and using the electrostatic adsorption to achieve spatial confinement, the Pt elements were mainly distributed on the exposed TiO2, thus generating the Pt/10EG-TiO2-10 catalyst. The best CO oxidation activity with the excellent resistance to H2O and SO2 was obtained over the Pt/10EG-TiO2-10 catalyst: CO conversion after 36 hr of the reaction was ca. 85% under the harsh condition of 10 vol.% H2O and 100 ppm SO2 at a high gaseous hourly space velocity (GHSV) of 400,000 hr-1. Physicochemical properties of the catalysts were characterized by various techniques. The results showed that the electrostatic adsorption, which riveted the Pt elements mainly on the exposed TiO2 of the support surface, reduced the dispersion of Pt NPs on EG and achieved the effective dispersion of Pt NPs, hence significantly improving CO oxidation activity over the Pt/10EG-TiO2-10 catalyst. The 10 wt.% EG doped in TiO2 caused the TiO2 support to form a more hydrophobic surface, which reduced the adsorption of H2O and SO2 on the catalyst, greatly inhibited deposition of the TiOSO4 and formation of the PtSO4 species as well as suppressed the oxidation of SO2, thus resulting in an improvement in the resistance to H2O and SO2 of the Pt/10EG-TiO2-10 catalyst.

Shattering the Water Window: Comprehensive Mapping of Faradaic Reactions on Bioelectronics Electrodes.

It is generally accepted that for safe use of neural interface electrodes, irreversible faradaic reactions should be avoided in favor of capacitive charge injection. However, in some cases, faradaic reactions can be desirable for controlling specific (electro)physiological outcomes or for biosensing purposes. This study aims to systematically map the basic faradaic reactions occurring at bioelectronic electrode interfaces. We analyze archetypical platinum-iridium (PtIr), the most commonly used electrode material in biomedical implants. By providing a detailed guide to these reactions and the factors that influence them, we offer a valuable resource for researchers seeking to suppress or exploit faradaic reactions in various electrode materials. We employed a combination of electrochemical techniques and direct quantification methods, including amperometric, potentiometric, and spectrophotometric assays, to measure O2, H2, pH, H2O2, Cl2/OCl-, and soluble platinum and iridium ions. We compared phosphate-buffered saline (PBS) with an unbuffered electrolyte and complex cell culture media containing proteins. Our results reveal that the "water window"─the potential range without significant water electrolysis─varies depending on the electrolyte used. In the culture medium that is rich with redox-active species, a window of potentials where no faradaic process occurs essentially does not exist. Under cathodic polarizations, significant pH increases (alkalization) were observed, while anodic water splitting competes with other processes in media, preventing prevalent acidification. We quantified the oxygen reduction reaction and accumulation of H2O2 as a byproduct. PtIr efficiently deoxygenates the electrolyte under low cathodic polarizations, generating local hypoxia. Under anodic polarizations, chloride oxidation competes with oxygen evolution, producing relatively high and cytotoxic concentrations of hypochlorite (OCl-) under certain conditions. These oxidative processes occur alongside PtIr dissolution through the formation of soluble salts. Our findings indicate that the conventional understanding of the water window is an oversimplification. Important faradaic reactions, such as oxygen reduction and chloride oxidation, occur within or near the edges of the water window. Furthermore, the definition of the water window significantly depends on the electrolyte composition, with PBS yielding different results compared with culture media.

Weekly carboplatin plus paclitaxel chemotherapy in advanced melanoma patients resistant to anti-PD-1 inhibitors: a retrospective, monocentric experience.

Immunotherapy with anti-PD-1 antibodies significantly improved the prognosis in advanced melanoma patients, but most of them develop primary or secondary resistance to the treatment. In this study, we evaluated efficacy and safety of a chemotherapy regimen with weekly carboplatin plus paclitaxel (wCP) in patients previously treated with anti-PD-1 antibodies. We retrospectively identified 30 patients with advanced melanoma treated at our Institute over the last eight years with wCP. The co-primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). In addition, we evaluated treatment tolerability. For this patient cohort, median PFS and OS were 3.25 and 7.69 months, respectively. All included patients had previously received anti-PD-1 immunotherapy, most of them had ECOG PS 0-1, and only 5 patients had a BRAF V600 mutation. In univariable analysis, we observed shorter OS in patients with > 2 involved metastatic sites, superficial spreading histology, and serum lactate dehydrogenase (LDH) values above the median. Liver metastases were associated with worse outcomes, while radiotherapy treatment of brain metastases was associated with improved OS. However, in a multivariable Cox regression model, only LDH above the median, superficial spreading histology, and female sex were significantly associated with worse OS. We reported grade 3 and 4 treatment-related toxicities in 4 and 0 patients, respectively. In conclusion, chemotherapy with wCP is a valid palliative treatment in advanced melanoma who progressed with anti-PD-1 antibodies.

Phase III randomized trial comparing neoadjuvant paclitaxel+platinum to 5-fluorouracil+platinum in esophageal/GEJ squamous cell carcinoma.

PURPOSE: Standard neoadjuvant chemotherapy (NACT) for locally advanced esophageal/gastroesophageal junction squamous cancer (LAEGSC), 5-fluorouracil (5FU)+platinum, is toxic and logistically challenging; alternative regimens are needed. PATIENTS AND METHODS: Phase III randomized open-label non-inferiority trial at Tata Memorial Center, India, in resectable LAEGSC. Patients were randomized 1:1 to three cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin AUC 6) with paclitaxel 175 mg/m2 (day 1) or 5FU 1000 mg/m2 continuous infusion (days 1-4), followed by surgery. RESULTS: Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Significantly more patients on paclitaxel + platinum (194 (92.3%)] received all 3 chemotherapy cycles than on 5FU+platinum (170 [85.9%]), P = .009. 5FU + platinum caused more grade ≥ 3 toxicities (124 [69.7%]) than paclitaxel + platinum (97 [51.9%]), P = .001. Surgery was performed in 131 (62.4%) patients on 5FU + platinum vs 139 (66.2%) on paclitaxel + platinum, P = .415. Paclitaxel + platinum resulted in higher pathologic primary tumor clearance (33 [25.8%]) vs 17 [15%]; P = .04), and pathologic complete responses in 21.9% compared to 12.4% from 5FU + platinum, P = .053. Median OS was 27.5 months (95% CI, 18.6-43.5) from paclitaxel + platinum, which was non-inferior to 27.1 months (95% CI, 18.8-40.7) from 5FU + platinum; HR, 0.89 (95% CI, 0.72-1.09); P = .346. CONCLUSION: Neoadjuvant paclitaxel + platinum chemotherapy is safer, and results in similar R0 resections, higher pathologic tumor clearance and non-inferior survival, compared to 5FU + platinum. Paclitaxel + platinum should replace 5FU + platinum as NACT for resectable LAEGSC. CLINICAL TRIALS REGISTRY INDIA NUMBER: CTRI/2014/04/004516.

Current HRD assays in ovarian cancer: differences, pitfalls, limitations, and novel approaches.

Ovarian carcinoma (OC) still represents an insidious and fatal malignancy, and few significant results have been obtained in the last two decades to improve patient survival. Novel targeted therapies such as poly (ADP-ribose) polymerase inhibitors (PARPi) have been successfully introduced in the clinical management of OC, but not all patients will benefit, and drug resistance almost inevitably occurs. The identification of patients who are likely to respond to PARPi-based therapies relies on homologous recombination deficiency (HRD) tests, as this condition is associated with response to these treatments. This review summarizes the genomic and functional HRD assays currently used in clinical practice and those under evaluation, the clinical implications of HRD testing in OC, and their current pitfalls and limitations. Special emphasis will be placed on the functional HRD assays under development and the use of machine learning and artificial intelligence technologies as novel strategies to overcome the current limitations of HRD tests for a better-personalized treatment to improve patient outcomes.

Hydrodeoxygenation of Isoeugenol-derived Model Compound over Carbon-supported Pt and Pt-SnS Catalysts for the Production of Sustainable Jet Fuel.

This study focuses on the sustainable production of bio-jet fuel through the catalytic hydrodeoxygenation (HDO) of isoeugenol (IE). Properties of two spraying synthesis methods (in situ and ex situ metal doping) with different platinum (Pt) loading percentages. The catalyst was characterised using various techniques such as XAS, X-ray photoelectron spectroscopy, X-ray diffraction, high-resolution transmission electron microscopy (HRTEM), field-emission scanning electron microscopy (FESEM) and thermogravimetric analysis. The HRTEM and FESEM results show the successful preparation of a spherical nanoparticle doped over activated carbon, and Pt was dispersed on the outer shell of the particles. The catalytic HDO of IE showed a high yield and conversion as follows: IE conversion of 100%, liquid-phase mass balance of 95.92%, dihydroeugenol conversion of 99.32%, propylcyclohexane yield of 88.94% and HYD yield of 76.19%. Moreover, the catalyst exhibited high reusability with low metal leaching and high coke resistance for 10 cycles. The catalyst was evaluated in a continuous flow reactor for 100 h at different reaction temperatures, and interestingly, the catalyst showed low deactivation with a high half-time.

Harnessing the Synergistic Interplay between Atomic-scale Vacancies and Ligand Effect to Optimize the Oxygen Reduction Activity and Tolerance Performance.

Defect engineering is an effective strategy for regulating the electrocatalysis of nanomaterials, yet it is seldom considered for modulating Pt-based electrocatalysts for the oxygen reduction reaction (ORR). In this study, we designed Ni-doped vacancy-rich Pt nanoparticles anchored on nitrogen-doped graphene (Vac-NiPt NPs/NG) with a low Pt loading of 3.5 wt.% and a Ni/Pt ratio of 0.038:1. Physical characterizations confirmed the presence of abundant atomic-scale vacancies in the Pt NPs induces long-range lattice distortions, and the Ni dopant generates a ligand effect resulting in electronic transfer from Ni to Pt. Experimental results and theoretical calculations indicated that atomic-scale vacancies mainly contributed the tolerance performances towards CO and CH3OH, the ligand effect derived from a tiny of Ni dopant accelerated the transformation from *O to *OH species, thereby improved the ORR activity without compromising the tolerance capabilities. Benefiting from the synergistic interplay between atomic-scale vacancies and ligand effect, as-prepared Vac-NiPt NPs/NG exhibited improved ORR activity, sufficient tolerance capabilities, and excellent durability. This study offers a new avenue for modulating the electrocatalytic activity of metal-based nanomaterials.

Tumor-Homing Phage Nanofibers for Nanozyme-Enhanced Targeted Breast Cancer Therapy.

Photodynamic therapy (PDT) eliminates cancer cells by converting endogenous oxygen into reactive oxygen species (ROS). However, its efficacy is significantly hindered by hypoxia in solid tumors. Hence, to engineer filamentous fd phage, a human-friendly bacteria-specific virus is proposed, into a nanozyme-nucleating photosensitizer-loaded tumor-homing nanofiber for enhanced production of ROS in a hypoxic tumor. Specifically, Pt-binding and tumor-homing peptides are genetically displayed on the sidewall and tip of the fd phage, respectively. The Pt-binding peptides induced nucleation and orientation of Pt nanozymes (PtNEs) on the sidewall of the phage. The resultant PtNE-coated tumor-homing phage exhibits significantly enhanced sustained catalytic conversion of hydrogen peroxide in hypoxic tumors into O2 for producing ROS needed for PDT, compared to non-phage-templated PtNE. Density functional theory (DFT) calculations verify the catalytic mechanism of the phage-templated PtNE. After intravenous injection of the PtNE-coated indocyanine green (ICG)-loaded tumor-homing phages into breast tumor-bearing mice, the nanofibers home to the tumors and effectively inhibit tumor growth by the PtNE-enhanced PDT. The nanofibers can also serve as a tumor-homing imaging probe due to the fluorescence of ICG. This work demonstrates that filamentous phage, engineered to become tumor-homing nanozyme-nucleating tumor-hypoxia-relieving nanofibers, can act as cancer-targeting nanozymes with improved catalytic performance for effective targeted PDT.

Green-light Hydrosilylation Photocatalysis with Platinum(II) Metalla-N-Heterocyclic Carbene Complexes.

Platinum(II) metalla-N-heterocyclic carbene complexes featuring pyridyl heterocyclic moiety demonstrate remarkable catalytic efficiency in alkyne hydrosilylation under green light irradiation. The photocatalytic properties of complexes are rationalised by the photo-induced charge transfer occurring in extended condensed system identified with the help of various experimental (UV/vis and emission spectroscopy, cyclic voltammetry) and theoretical methods (DFT/TD-DFT, IFCT analysis).

D-Band Center Engineered Pt-Based Nanozyme for Personalized Pharmacovigilance.

A high-efficiency PtZnCd nanozyme was screened with density functional theory (DFT) and unique d-orbital coupling features for sensitive enrichment and real-time analysis of CO-releasing molecule-3 (CORM-3). Multi-catalytic sites in the nanozyme showed a high reactivity of up to 72.89 min-1 for peroxidase-like enzymes (POD) reaction, which was 2.2, 4.07, and 14.67 times higher than that of PtZn (32.67 min-1), PtCd (17.89 min-1), and Pt (4.97 min-1), respectively. Normalization of the catalytic sites showed that the catalytic capacity of the active site in PtZnCd was 2.962 U µmol-1, which was four times higher than that of pure Pt site (0.733 U µmol-1). DFT calculations showed that improved d-orbital coupling between different metals reduces the position of the center of the shifted whole d-band relative to the Fermi energy level, thereby increasing the contribution of the sites to the electron transfer from the active center, accompanied with enhanced substrate adsorption and intermediate conversion in the catalytic process. The potential adsorption principle and color development mechanism of CORM-3 on PtZnCd were determined, and the practical application in drug metabolism was validated in vitro, in zebrafish and mice as a model, demonstrating that transition metal doping effectively engineers high-performance nanozymes and optimizes artificial enzymes.

Platinum Elimination From Bis(triethylsilylpolyynyl) Complexes and Macrocycles Comprised of Four L2Pt Corners and Four CΞCCΞCCΞC Linkers; An Approach to Cyclo[24]carbon.

The overarching goal of this study is to effect the elimination of platinum from adducts with cis -CΞC-Pt-CΞC- linkages, thereby generating novel conjugated polyynes. Thus, the bis(hexatriynyl) complex trans-(p-tol3P)2Pt((CΞC)3H)2 is treated with 1,3-diphosphines R2C(C-H2PPh2)2 to generate (R2C(CH2PPh2)2)2Pt((CΞC)3H)2 (14; R = c, n-Bu; e, p-tolCH2). These con-dense with the diiodide complexes R2C(CH2PPh2)2PtI2 (9a,c) in the presence of CuI (cat.) and excess HNEt2 to give the title macrocycles [(R2C(CH2PPh2)2)Pt(CΞC)3]4 (16c,e) as adducts of the byproduct [H2NEt2]+ I- (30-66%). DOSY NMR experiments establish that this association is maintained in solution, but NaOAc removes the ammonium salt. The bis(triethylsilylpolyynyl) complexes (n-Bu2C(CH2PPh2)2)Pt((CΞC)nSiEt3)2 (n = 2, 3) are synthesized analogously to 14c. They react with I2 at rt to give mainly the diiodide complex 9c and the coupling product Et3Si(CΞCCΞC)nSiEt3. The possibility of competing reactions giving ICΞC species is investigated. Analogous reactions of the Pt4C24 macrocycle 16c also give 9c, but no sp 13C NMR signals or mass spectrometric Cxz+ ions (x = 24-100) could be detected. It is proposed that some cyclo[24]car-bon is generated, but then rapidly converts to other forms of elemental carbon. No cyclotetracosane (C24H48) is detected when this sequence is carried out in the presence of PtO2 and H2.

Interval to Recurrence Affects Survival in Recurrent Head and Neck Squamous Cell Carcinoma.

Background/Aim: Approximately half of head and neck squamous cell carcinoma (HNSCC) cases recur, with most recurrences occurring within the first two years after treatment. Although it has been suggested that the interval to recurrence after radical treatment is associated with prognosis in patients with HNSCC, further investigation is needed. Patients and Methods: Patients diagnosed with HNSCC at Kyushu University Hospital were retrospectively analyzed (n=500). Early recurrence (ER) was defined as disease recurrence within six months of radical treatment, whereas late recurrence (LR) was defined as recurrence after more than six months. Continuous variables were assessed using the Mann-Whitney U-test and categorical variables were assessed using Fisher's exact test. Results: A total of 234 patients experienced recurrence, with 110 and 124 patients experiencing ER (recurrence within two to six months) and LR (recurrence after six months), respectively. Multivariate analyses identified two independent risk factors for poor prognosis: ER [hazard ratio (HR)=3.200, 95% confidence interval (CI)=1.570-6.521, p=0.001] and absence of radiotherapy (HR=0.374, 95%CI=0.191-0.733, p=0.004). In patients with recurrent HNSCC, a short interval to recurrence is a risk factor for poor prognosis and survival. This study demonstrated the prognostic value of ER in these patients. Conclusion: The selection of treatment for patients with recurrent head and neck squamous cell carcinoma should consider the timing of recurrence, the initial treatment regimen, and the strategy for changing salvage therapy depending on the recurrence status.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor.

BACKGROUND: Germ cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. METHODS: This retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. RESULTS: The study included 37 male patients with a median age of 26 years (range: 18-65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. CONCLUSIONS: Immunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Genetic polymorphisms and platinum-induced hematological toxicity: a systematic review.

Background: Platinum-based chemotherapy bring severe hematological toxicity that can lead to dose reduction or discontinuation of therapy. Genetic variations have been reported to influence the risk and extent of hematological toxicity; however, the results are controversial and a comprehensive overview is lacking. This systematic review aimed to identify genetic biomarkers of platinum-induced hematological toxicity. Method: Pubmed, Embase and Web of science database were systematically reviewed for studies that evaluated the association of genetic variants and platinum-related hematological toxicity in tumor patients with no prior history of chemotherapy or radiation, published from inception to the 28th of January 2022. The studies should have specific toxicity scoring system as well as defined toxicity end-point. The quality of reporting was assessed using the Strengthening the Reporting of Genetic Association Studies (STREGA) checklist. Results were summarized using narrative synthesis. Results: 83 studies were eligible with over 682 single-nucleotide polymorphisms across 110 genes. The results are inconsistent and diverse with methodological issues including insufficient sample size, population stratification, various treatment schedule and toxicity end-point, and inappropriate statistics. 11 SNPs from 10 genes (ABCB1 rs1128503, GSTP1 rs1695, GSTM1 gene deletion, ERCC1 rs11615, ERCC1 rs3212986, ERCC2 rs238406, XPC rs2228001, XPCC1 rs25487, MTHFR rs1801133, MDM2 rs2279744, TP53 rs1042522) had consistent results in more than two independent populations. Among them, GSTP1 rs1695, ERCC1 rs11615, ERCC1 rs3212986, and XRCC1 rs25487 present the most promising results. Conclusion: Even though the results are inconsistent and several methodological concerns exist, this systematic review identified several genetic variations that deserve validation in well-defined studies with larger sample size and robust methodology. Systematic Review Registration: https://www.crd.york.ac.uk/, identifier CRD42021234164.

Nanostructured mesoporous silica carriers for platinum-based conjugates with anti-inflammatory agents.

This review discusses the relationship between inflammation and cancer initiation and progression, which has prompted research into anti-inflammatory approaches for cancer prevention and treatment. Specifically, it focuses on the use of inflammation-reducing agents to enhance the effectiveness of tumor treatment methods. These agents are combined with platinum(II)-based antitumor drugs to create multifunctional platinum(IV) prodrugs, allowing for simultaneous delivery to tumor cells in a specific ratio. Once inside the cells and subjected to intracellular reduction, both components can act in parallel through distinct pathways. Motivated by the objective of reducing the systemic toxicity associated with contemporary chemotherapy, and with the aim of leveraging the passive enhanced permeability and retention effect exhibited by nanostructured materials to improve their accumulation within tumor tissues, the platinum(IV) complexes have been efficiently loaded into mesoporous silica SBA-15 material. The resulting nanostructured materials are capable of providing controlled release of the conjugates when subjected to simulated plasma conditions. This feature suggests the potential for extended circulation within the body in vivo, with minimal premature release of the drug before reaching the intended target site. The primary emphasis of this review is on research that integrates these two approaches to develop chemotherapeutic treatments that are both more efficient and less harmful.

Ferrostatin-1 ameliorates Cis-dichlorodiammineplatinum(II)-induced ovarian toxicity by inhibiting ferroptosis.

Cis-dichlorodiammineplatinum(II) (CDDP), while widely utilized in tumor therapy, results in toxic side effects that patients find intolerable. The specific mechanism by which CDDP inflicts ovarian damage remains unclear. This study aimed to explore the involvement of ferrostatin-1 (FER-1) and ferroptosis in CDDP-induced ovarian toxicity. This study established models of CDDP-induced injury in granulosa cells (GCs) and rat model of premature ovarian failure (POF). CCK-8 assessed the effects of CDDP and FER-1 on GC viability. FerroOrange and Mito-FerroGreen, DCFH-DA and MitoSox-Red, Rhodamine 123 and Transmission electron microscopy (TEM) measured Fe2+, reactive oxygen species (ROS), mitochondrial membrane potential and the mitochondrial morphology in GC cells, respectively. Serum hormone levels; organ indices; malondialdehyde, superoxide dismutase, and glutathione analyses; and western blotting were performed to examine ferroptosis's role in vitro. Molecular docking simulation was evaluated the interaction between FER-1 and GPX4 or FER-1 and NRF2. Molecular docking simulations were conducted to evaluate the interactions between FER-1 and GPX4, as well as FER-1 and NRF2. The findings revealed that CDDP-induced ovarian toxicity involved iron accumulation, increased ROS accumulation, and mitochondrial dysfunction, leading to endocrine disruption and tissue damage in rats. These changes correlated with NRF2, HO-1, and GPX4 levels. However, FER-1 decreased the extent of ferroptosis. Thus, ferroptosis appears to be a crucial mechanism of CDDP-induced ovarian injury, with GPX4 as potential protective targets.

Diphenylamino-Modified Neutral Pt(II) Complexes: Their Aggregation-Induced Phosphorescent Emission and Picric Acid-Sensing Properties.

Three neutral Pt(II) complexes with diphenylamino-modified 2-phenylpyridine derivatives as cyclometalating ligands and acetylacetone as the ancillary ligand exhibit aggregation-induced phosphorescent emission (AIPE) properties in THF/H2O. The crystal structures of the complexes highlight the contributions of non-covalent Pt···Pt interactions and hydrogen bonds to the AIPE properties. These AIPE-active Pt(II) complexes 1-3 have been successfully applied to detect picric acid (PA) in aqueous media, affording the lowest limit of detection at 70 nM. Furthermore, three Pt(II) complexes are able to detect PA in common water samples. The quenching of luminescence in the detection can be attributed to photo-induced electron transfer.

Split-Dose Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Carcinoma: A Systematic Literature Review and Network Meta-Analysis.

BACKGROUND: Gemcitabine plus cisplatin (GC) is a highly active and commonly used regimen in locally advanced/metastatic urothelial carcinoma (la/mUC). With GC, cisplatin is dosed at 70 mg/m2 on day 1 of a 3-week cycle; however, for many patients, impaired renal or cardiac function, neuropathy, or poor performance status (PS) can preclude the use of cisplatin. A promising alternative is split-dose GC, in which the cisplatin dose is divided over 2 days. METHODS: We conducted a systematic literature review (SLR) and network meta-analysis (NMA) to better understand treatment patterns and comparative effectiveness and safety of split-dose GC vs gemcitabine plus carboplatin (GCa), GC, and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). RESULTS: Among 120 identified studies, 16 studies representing 1,767 patients included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function, age > 70 years, comorbidities, and physician preference. Split-dose GC had objective response rates (ORRs) of 39%-80%, median progression-free survival (PFS) of 3.5-9.9 months, and median overall survival (OS) of 8.5-18.1 months. Discontinuation rates due to adverse events were 5%-38%. In the NMA, ORR with split-dose GC was significantly higher than with GCa. PFS and OS for split-dose GC were similar to that observed with the other regimens (GCa, GC, and MVAC). CONCLUSIONS: This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, split-dose GC demonstrated comparable effectiveness and safety profile to those seen with other regimens. Split-dose GC thus has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further prospective study.

The Reactivity of Ptn + Clusters With N2O Facilitated by Dual Lewis-Acid Sites.

The size dependence of metal cluster reactions frequently reveals valuable information on the mechanism of nanometal catalysis. Here, the reactivity of the Ptn + (n = 1-40) clusters with N2O is studied and a significant dependence on the size of these clusters is noticed. Interestingly, the small Ptn + clusters like Pt3 + and Pt4 + are inclined to form N2O complexes; some larger clusters, such as Pt19 +, Pt21 +, and Pt23 +, appear to be unreactive; however, the others such as Pt3 , 9,15 + and Pt18 + are capable of decomposing N2O. While Pt9 + rapidly reacts with N2O to form a stable quasitetrahedron Pt9O+ product, Pt18 + experiences a series of N2O decompositions to produce Pt18O1-7 +. Utilizing high-precision theoretical calculations, it is shown how the atomic structures and active sites of Ptn + clusters play a vital role in determining their reactivity. Cooperative dual Lewis-acid sites (CDLAS) can be achieved on specific metal clusters like Pt18 +, rendering accelerated N2O decomposition via both N- and O-bonding on the neighboring Pt atoms. The influence of CDLAS on the size-dependent reaction of Pt clusters with N2O is illustrated, offering insights into cluster catalysis in reactions that include the donation of electron pairs.

Efficacy of a platinum-based chemotherapy rechallenge for platinum-sensitive recurrence after PARP inhibitor maintenance.

Objective: Platinum-free interval (PFI) is the period from the end of platinum-based chemotherapy to the date of recurrence. If the PFI is > 6 months, a platinum-based chemotherapy rechallenge is considered; however, its efficacy after poly adenosine 5'-diphosphate-ribose polymerase (PARP) inhibitor maintenance therapy is unknown. This study aimed to examine the efficacy of a platinum-based chemotherapy rechallenge after PARP inhibitor therapy. Methods: We retrospectively evaluated patients with ovarian cancer with a PFI≥6 months with PARP inhibitor maintenance therapy, receiving platinum-based chemotherapy. Duration of PARP inhibitor therapy, best response to subsequent platinum chemotherapy rechallenge, and clinical characteristics were collected from medical records. Tumor response was assessed according to RECIST 1.1. Correlations were calculated using Spearman's correlation coefficients. Results: Among the 10 included patients, seven (70 %) received PARP inhibitors after primary chemotherapy, and three (30 %) received chemotherapy for platinum-sensitive relapse. One and five patients harbored a germline BRCA1 and BRCA wild-type mutations, respectively, and two had homologous recombination proficiency. The median PFI was 303.5 (182-602) days, and PARP inhibitor therapy duration was 249 (147-570) days. Platinum chemotherapy rechallenge efficacy was complete and partial response and stable disease in one (10 %), six (60 %), and three (30 %) patients, respectively. The longer the duration of PARP inhibitor treatment, better the response to platinum agents (Spearman correlation coefficient 0.284, p = 0.0288). Conclusion: Platinum-based chemotherapy rechallenge is reasonable for patients with platinum-sensitive disease, using the traditional PFI cutoff of 6 months, even when the PFI is obtained with a maintenance PARP inhibitor.