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Oncoimmunology 2022Epithelial ovarian carcinoma (EOC) is virtually insensitive to immune checkpoint inhibitors (ICIs). Recent findings from an innovative mouse model of EOC demonstrate...
Epithelial ovarian carcinoma (EOC) is virtually insensitive to immune checkpoint inhibitors (ICIs). Recent findings from an innovative mouse model of EOC demonstrate that senescence induction underlies the increased sensitivity of homologous recombination-defective EOCs to platinum-based chemotherapy as it initiates tumor infiltration by immune effector cells coupled to restored sensitivity to ICIs.
Topics: Animals; Carcinoma, Ovarian Epithelial; Cellular Senescence; Female; Mice; Ovarian Neoplasms; Platinum; Tumor Microenvironment
PubMed: 35309729
DOI: 10.1080/2162402X.2022.2052411 -
Pharmacological Research Jan 2023Traditional platinum-based anticancer drugs, led by cisplatin, play an important role in chemotherapy. However, the development of platinum compounds is limited due to...
Traditional platinum-based anticancer drugs, led by cisplatin, play an important role in chemotherapy. However, the development of platinum compounds is limited due to serious toxicity and side effects. In recent years, studies have showed that immunogenic cell death (ICD) may be one of the potential action mechanisms of classical platinum drugs, such as oxaliplatin. This strategy combining chemotherapy and immunotherapy can effectively utilize the body's immune system to help platinum compounds to fight against tumors, and the dose can be appropriately reduced to limit toxic side effects. The induction of ICD by platinum compounds has become a research hotspot and one of the future development directions of metal drugs. Here, the progress of platinum compounds were collected and comprehensively summarized, their capacity of ICD induction and mechanism of action are exposed, providing reference for the design and synthesis of new anticancer platinum ICD inducers.
Topics: Platinum; Immunogenic Cell Death; Antineoplastic Agents; Cisplatin; Platinum Compounds
PubMed: 36403722
DOI: 10.1016/j.phrs.2022.106556 -
Molecules (Basel, Switzerland) Dec 2022Transition metal complexes have continued to constitute an appealing class of medicinal compounds since the exceptional discovery of cisplatin in the late 1960s....
Transition metal complexes have continued to constitute an appealing class of medicinal compounds since the exceptional discovery of cisplatin in the late 1960s. Pt(II)-based complexes are endowed with a broad range of biological properties, which are mainly exerted by targeting DNA. In this study, we report a significant biological investigation into and computation analyses of four Pt(II)-complexes, namely, , synthesized and characterized according to previously reported procedures. Molecular-modelling studies highlighted that the top two compounds (i.e., and ) might bind to both matched and mismatched base pair sites of the oligonucleotide 5'-(dCGGAAATTACCG)-3', supporting their anticancer potential. These two complexes displayed noteworthy cytotoxicity in vitro (sub-micromolar-micromolar range) against two leukaemia cell lines, i.e., CCRF-CEM and its multi-drug-resistant counterpart CEM/ADR5000, and remarkable anti-angiogenic properties (in the sub-micromolar range) evaluated in an in vivo model, i.e., a chick embryo chorioallantoic membrane (CAM) assay.
Topics: Animals; Chick Embryo; Platinum; Antineoplastic Agents; Coordination Complexes; Cisplatin; DNA; Cell Line, Tumor
PubMed: 36558133
DOI: 10.3390/molecules27249000 -
Zhongguo Fei Ai Za Zhi = Chinese... Sep 2015Platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors, lung... (Review)
Review
Platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors, lung cancer, and colorectal cancer. Two major problems exist, however, in the clinic use of platinum derivatives. One is the development of tumor resistance to the drug during therapy, leading to treatment failure. The other is the drug's toxicity such as the cisplatin's nephrotoxicity, which limits the dose that can be administered. This paper describes the mechanism of platinum derivatives induced kidney injury.
Topics: Antineoplastic Agents; Humans; Kidney; Platinum
PubMed: 26383983
DOI: 10.3779/j.issn.1009-3419.2015.09.09 -
Sensors (Basel, Switzerland) Jun 2022The application of direct current (DC) produces a rapid and reversible nerve conduction block. However, prolonged injection of charge through a smooth platinum electrode...
The application of direct current (DC) produces a rapid and reversible nerve conduction block. However, prolonged injection of charge through a smooth platinum electrode has been found to cause damage to nervous tissue. This damage can be mitigated by incorporating high-capacitance materials (HCM) (e.g., activated carbon or platinum black) into electrode designs. HCMs increase the storage charge capacity (i.e., "Q value") of capacitive devices. However, consecutive use of these HCM electrodes degrades their surface. This paper evaluates activated carbon and platinum black (PtB) electrode designs in vitro to determine the design parameters which improve surface stability of the HCMs. Electrode designs with activated carbon and PtB concentrations were stressed using soak, bend and vibration testing to simulate destructive in vivo environments. A Q value decrease represented the decreased stability of the electrode-HCM interface. Soak test results supported the long-term Q value stabilization (mean = 44.3 days) of HCM electrodes, and both HCMs displayed unique Q value changes in response to soaking. HCM material choices, Carbon Ink volume, and application of Nafion™ affected an electrode's ability to resist Q value degradation. These results will contribute to future developments of HCM electrodes designed for extended DC application for in vivo nerve conduction block.
Topics: Charcoal; Electric Capacitance; Electricity; Electrodes; Platinum
PubMed: 35684899
DOI: 10.3390/s22114278 -
Journal of Thoracic Oncology : Official... Dec 2021Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study....
Updated Overall Survival Data and Predictive Biomarkers of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC in the Phase 3 ORIENT-11 Study.
INTRODUCTION
Sintilimab plus chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy alone in nonsquamous NSCLC in the ORIENT-11 study. Updated overall survival (OS) and PFS data and corresponding biomarker analyses are reported here.
METHODS
In this study, a total of 397 patients with previously untreated, locally advanced or metastatic nonsquamous NSCLC were assigned to sintilimab plus chemotherapy combination treatment (combo) group or placebo plus chemotherapy treatment group. The patients were stratified by programmed death-ligand 1 (PD-L1) expression levels. Immune signature profiles from tumor RNA sequencing and PD-L1 immunohistochemistry were correlated with clinical outcome to identify predictive biomarkers.
RESULTS
As of January 2021, with median follow-up of 22.9 months, median OS was significantly improved in the combo group compared with the placebo plus chemotherapy treatment group (not reached versus 16.8 mo; hazard ratio [HR] = 0.60, 95% confidence interval [CI]: 0.45-0.79, p = 0.0003). High or medium immune cell infiltration was strongly associated with improved PFS in the combo group, in contrast to absent or low immune cell infiltration, which suggests that chemotherapy could not prime "immune deserts" to obtain benefit from programmed cell death protein-1 inhibition. In particular, high major histocompatibility complex (MHC) class II presentation pathway expression was significantly correlated with prolonged PFS (HR = 0.32, 95% CI: 0.19-0.54, p < 0.0001) and OS (HR = 0.36, 95% CI: 0.20-0.64, p = 0.0005) in the combo group. Importantly, patients with low or absent PD-L1 but high MHC class II expression could still benefit from the combo treatment. In contrast, MHC class I antigen presentation pathway was less relevant in this combination setting.
CONCLUSIONS
The addition of sintilimab to chemotherapy resulted to significantly longer OS in nonsquamous NSCLC. Expression of MHC class II antigen presentation pathway could identify patients benefiting most from this combination.
Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Humans; Lung Neoplasms; Pemetrexed; Platinum
PubMed: 34358724
DOI: 10.1016/j.jtho.2021.07.015 -
Molecules (Basel, Switzerland) Oct 2022Rollover cyclometalated complexes constitute a family of derivatives which differ from classical cyclometalated species in certain aspects. Various potential application...
Rollover cyclometalated complexes constitute a family of derivatives which differ from classical cyclometalated species in certain aspects. Various potential application fields have been developed for both classes of compounds, which have both similarities and differences. In order to uncover the relationships and distinctions between these two families of compounds, four Pt(II) cyclometalated complexes derived from 2-phenylpyridine (ppy) and 2,2'-bipyridine (bpy), assumed as prototypical ligands, were compared. For this study, an electron rich isostructural and isoelectronic pair of compounds, [Pt(N^C)Me(PPh)], and an electron-poorer compound, [Pt(N^C)Cl(PPh)] were chosen (N^C = ppy or bpy). DFT calculations, cyclic voltammetry, and UV-Vis spectra also helped to shed light into these species. Due to the presence of the more electronegative nitrogen in place of a C-H group, the rollover bpy-H ligand becomes a slightly weaker donor than the classical ppy-H ligand, and hence, generates (slightly) more stable cyclometalated complexes, lower energy frontier molecular orbitals, and electron-poorer platinum centers. On the whole, it was revealed that classical and rollover complexes have overall structural similarity, which contrasts to their somewhat different chemical behavior.
Topics: Ligands; Crystallography, X-Ray; Platinum; Electrons; Nitrogen
PubMed: 36364075
DOI: 10.3390/molecules27217249 -
Oncoimmunology 2020
Topics: Antineoplastic Agents; Humans; Immunogenic Cell Death; Neoplasms; Platinum
PubMed: 32117595
DOI: 10.1080/2162402X.2020.1729022 -
Chemico-biological Interactions Feb 2020Cisplatin (CisPt) and other platinum (Pt)-based antineoplastic drugs (e.g., carboplatin, oxaliplatin) are highly effective and widely used in the treatment of solid...
Cisplatin (CisPt) and other platinum (Pt)-based antineoplastic drugs (e.g., carboplatin, oxaliplatin) are highly effective and widely used in the treatment of solid tumors in both pediatric and adult patients. Although considered to be life-saving as a cancer treatment, Pt-based drugs frequently result in dose-limiting toxicities such as chemotherapy-induced peripheral neuropathies (CIPN). Specifically, irreversible damage to outer hair cells and injury of sensory neurons are linked to profound sensorineural hearing loss (ototoxicity), which complicates tumor management and can lead to a poor clinical prognosis. Given the severity of CIPN, substantial effort has been devoted to the development of neuroprotective compounds, regardless clinical results have been underwhelming. It is noteworthy that Pt is a highly reactive electrophile (electron deficient) that causes toxicity by forming adducts with nucleophilic (electron rich) targets on macromolecules. In this regard, we have discovered a series of carbon-based enol nucleophiles; e.g., N-(4-acetyl-3,5-dihydroxyphenyl)-2-oxocytclopentane-1-carboxamide (Gavinol), that can prevent neurotoxicity by scavenging the platinum ion. The chemistry of enol compounds is well understood and mechanistic research has demonstrated the role of this chemistry in cytoprotection. Our cell-derived data were corroborated by calculations of hard and soft, acids and bases (HSAB) parameters that describe the electronic character of interacting electrophiles and nucleophiles. Together, these observations indicate that the respective mechanisms of Pt neurotoxicity and antitumor activity are separable and can therefore be affected independently.
Topics: Animals; Antineoplastic Agents; Cells, Cultured; Humans; Male; Mice; Neurotoxicity Syndromes; Organoplatinum Compounds; Peripheral Nervous System Diseases; Platinum; Rats
PubMed: 31978392
DOI: 10.1016/j.cbi.2020.108961 -
Molecules (Basel, Switzerland) Sep 2022Ageing processes of vehicle catalytic converters inevitably lead to the release of Pt and Pd into the environment, road dust being the main sink. Though Pt and Pd are...
Ageing processes of vehicle catalytic converters inevitably lead to the release of Pt and Pd into the environment, road dust being the main sink. Though Pt and Pd are contained in catalytic converters in nanoparticulate metallic form, under environmental conditions, they can be transformed into toxic dissolved species. In the present work, the distribution of Pt and Pd between dissolved, nanoparticulate, and microparticulate fractions of Moscow road dust is assessed. The total concentrations of Pt and Pd in dust vary in the ranges 9-142 ng (mean 35) and 155-456 (mean 235) ng g, respectively. The nanoparticulate and dissolved species of Pt and Pd in dust were studied using single particle inductively coupled plasma mass spectrometry. The median sizes of nanoparticulate Pt and Pd were 7 and 13 nm, respectively. The nanoparticulate fraction of Pt and Pd in Moscow dust is only about 1.6-1.8%. The average contents of dissolved fraction of Pt and Pd are 10.4% and 4.1%, respectively. The major fractions of Pt and Pd (88-94%) in road dust are associated with microparticles. Although the microparticulate fractions of Pt and Pd are relatively stable, they may become dissolved under changing environmental conditions and, hence, transformed into toxic species.
Topics: Dust; Environmental Monitoring; Palladium; Platinum; Rhodium; Vehicle Emissions
PubMed: 36144840
DOI: 10.3390/molecules27186107