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Magyar Onkologia Mar 2020Germinal or somatic mutations of the BRCA genes may serve as therapeutic targets. Deficient functioning of the BRCA genes render the cancer vulnerable to such... (Review)
Review
Germinal or somatic mutations of the BRCA genes may serve as therapeutic targets. Deficient functioning of the BRCA genes render the cancer vulnerable to such therapeutic interventions as chemotherapy with DNA-targeted agents and PARP inhibitors targeting DNA repair capacity. Although BRCA mutations may be detected in a large variety of cancers, the mentioned specific therapies are efficient in the so called BRCA-associated cancers only including ovarian, breast, pancreatic, prostate cancers and the rare uterine sarcomas. While in ovarian and prostate carcinomas both germinal and somatic, in breast and pancreatic cancers exclusively germinal, and in uterine sarcomas mostly somatic mutations specify the tumor as BRCA-dependent; platinum-sensitivity in ovarian cancer may replace BRCA testing by indicating the presence of frequent DNA repair deficiency. Platinum-based chemotherapy is frequently efficient in BRCA-dependent cancers, while PARP inhibitors yet registered for ovarian, breast and pancreatic cancers bring paradigm change in the treatment of ovarian cancer and provide an additional treatment option of the others.
Topics: Genes, BRCA1; Genes, BRCA2; Humans; Mutation; Neoplasms; Platinum; Poly(ADP-ribose) Polymerase Inhibitors
PubMed: 32181758
DOI: No ID Found -
The Science of the Total Environment Dec 2022Documenting anaerobic conditions is critical for understanding soil processes, identifying hydric soils, delineating wetlands, and managing aquatic resources. Several... (Review)
Review
Documenting anaerobic conditions is critical for understanding soil processes, identifying hydric soils, delineating wetlands, and managing aquatic resources. Several techniques exist to evaluate the oxidation-reduction status of soils including platinum electrodes, chemical dyes, and analyses of porewater chemistry. Since 2002, Indicator of Reduction in Soils (IRIS) devices have proven a novel, reliable, and cost-effective technique to document anaerobic conditions. This technology involves the application of redox active Fe or Mn oxide based paints onto a durable substrate (e.g., Polyvinyl Chloride pipes or plastic films) which are inserted into the soil. If anaerobic conditions occur during deployment, some or all of the redox active paint will be depleted from the IRIS device surface via chemical reduction and the extent of paint removal can be quantified using a number of approaches. Over the last two decades, IRIS technology has evolved to improve the identification of anaerobic conditions in soils and provide a proxy measure of multiple soil biogeochemical processes (e.g., denitrification, elemental sorption, iron sulfide formation). This review paper provides an overview of developments in IRIS instrumental design and interpretation of results, describes current IRIS applications and benefits, and identifies potential future areas of IRIS device research.
Topics: Soil; Polyvinyl Chloride; Platinum; Iron; Oxidation-Reduction; Oxides; Coloring Agents
PubMed: 36055507
DOI: 10.1016/j.scitotenv.2022.158419 -
Biomolecules Dec 2019Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these... (Review)
Review
Along with surgery and radiotherapy, chemotherapeutic agents belong to the therapeutic arsenal in cancer treatment. In addition to their direct cytotoxic effects, these agents also impact the host immune system, which might enhance or counteract their antitumor activity. The platinum derivative compounds family, mainly composed of carboplatin, cisplatin and oxaliplatin, belongs to the chemotherapeutical arsenal used in numerous cancer types. Here, we will focus on the effects of these molecules on antitumor immune response. These compounds can induce or not immunogenic cell death (ICD), and some strategies have been found to induce or further enhance it. They also regulate immune cells' fate. Platinum derivatives can lead to their activation. Additionally, they can also dampen immune cells by selective killing or inhibiting their activity, particularly by modulating immune checkpoints' expression.
Topics: Animals; Antineoplastic Agents; Humans; Immune System; Immunologic Factors; Neoplasms; Platinum
PubMed: 31861811
DOI: 10.3390/biom10010013 -
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 -
Proceedings of the National Academy of... Sep 2022Electrocatalytic hydrogen evolution reaction (HER) is critical for green hydrogen generation and exhibits distinct pH-dependent kinetics that have been elusive to...
Electrocatalytic hydrogen evolution reaction (HER) is critical for green hydrogen generation and exhibits distinct pH-dependent kinetics that have been elusive to understand. A molecular-level understanding of the electrochemical interfaces is essential for developing more efficient electrochemical processes. Here we exploit an exclusively surface-specific electrical transport spectroscopy (ETS) approach to probe the Pt-surface water protonation status and experimentally determine the surface hydronium pK [Formula: see text] 4.3. Quantum mechanics (QM) and reactive dynamics using a reactive force field (ReaxFF) molecular dynamics (RMD) calculations confirm the enrichment of hydroniums (HO[Formula: see text]) near Pt surface and predict a surface hydronium pK of 2.5 to 4.4, corroborating the experimental results. Importantly, the observed Pt-surface hydronium pK correlates well with the pH-dependent HER kinetics, with the protonated surface state at lower pH favoring fast Tafel kinetics with a Tafel slope of 30 mV per decade and the deprotonated surface state at higher pH following Volmer-step limited kinetics with a much higher Tafel slope of 120 mV per decade, offering a robust and precise interpretation of the pH-dependent HER kinetics. These insights may help design improved electrocatalysts for renewable energy conversion.
Topics: Electrochemistry; Hydrogen; Hydrogen-Ion Concentration; Kinetics; Platinum; Renewable Energy; Water
PubMed: 36122216
DOI: 10.1073/pnas.2208187119 -
International Journal of Molecular... Jun 2022(1) Background: Since the discovery of cisplatin’s cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug...
Novel Nickel(II), Palladium(II), and Platinum(II) Complexes with , Bidendate Cinnamic Acid Ester Derivatives: An In Vitro Cytotoxic Comparison to Ruthenium(II) and Osmium(II) Analogues.
(1) Background: Since the discovery of cisplatin’s cytotoxic properties, platinum(II) compounds have attracted much interest in the field of anticancer drug development. Over the last few years, classical structure−activity relationships (SAR) have been broken by some promising new compounds based on platinum or other metals. We focus on the synthesis and characterization of 17 different complexes with β-hydroxydithiocinnamic acid esters as O,S bidendate ligands for nickel(II), palladium(II), and platinum(II) complexes. (2) Methods: The bidendate compounds were synthesized and characterized using classical methods including NMR spectroscopy, MS spectrometry, elemental analysis, and X-ray crystallography, and their cytotoxic potential was assessed using in vitro cell culture assays. Data were compared with other recently reported platinum(II), ruthenium(II), and osmium(II) complexes based on the same main ligand system. (3) Results: SAR analyses regarding the metal ion (M), and the alkyl-chain position (P) and length (L), revealed the following order of the effect strength for in vitro activity: M > P > L. The highest activities have Pd complexes and ortho-substituted compounds. Specific palladium(II) complexes show lower IC50 values compared to cisplatin, are able to elude cisplatin resistance mechanisms, and show a higher cancer cell specificity. (4) Conclusion: A promising new palladium(II) candidate (Pd3) should be evaluated in further studies using in vivo model systems, and the identified SARs may help to target platinum-resistant tumors.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cinnamates; Cisplatin; Coordination Complexes; Esters; Ligands; Nickel; Osmium; Palladium; Platinum; Ruthenium
PubMed: 35743112
DOI: 10.3390/ijms23126669 -
Nature Communications May 2022Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation...
Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use.
Topics: Animals; Antioxidants; Humans; Liver; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Platinum; Reactive Oxygen Species; Reperfusion Injury
PubMed: 35523769
DOI: 10.1038/s41467-022-29772-w -
Chembiochem : a European Journal of... Feb 2021Three chiral tridentate N^N^S coordinating pyridine-carbaldehyde (S)-N4-(α-methylbenzyl)thiosemicarbazones (HTSCmB) were synthesised along with lysine-modified...
Three chiral tridentate N^N^S coordinating pyridine-carbaldehyde (S)-N4-(α-methylbenzyl)thiosemicarbazones (HTSCmB) were synthesised along with lysine-modified derivatives. One of them was selected and covalently conjugated to the cell-penetrating peptide sC18 by solid-phase peptide synthesis. The HTSCmB model ligands, the HTSCLp derivatives and the peptide conjugate rapidly and quantitatively form very stable Pt chlorido complexes [Pt(TSC)Cl] when treated with K PtCl in solution. The Pt(CN) derivatives were obtained from one TSCmB model complex and the peptide conjugate complex through Cl →CN exchange. Ligands and complexes were characterised by NMR, IR spectroscopy, HR-ESI-MS and single-crystal XRD. Intriguingly, no decrease in cell viability was observed when testing the biological activity of the lysine-tagged HdpyTSCLp, its sC18 conjugate HdpyTSCL-sC18 or the PtCl and Pt(CN) conjugate complexes in three different cell lines. Thus, given the facile and effective preparation of such Pt-TSC-peptide conjugates, these systems might pave the way for future use in late-stage labelling with Pt radionuclides and application in nuclear medicine.
Topics: Cell-Penetrating Peptides; Humans; Lysine; Organometallic Compounds; Peptide Fragments; Platinum; Thiosemicarbazones
PubMed: 32909347
DOI: 10.1002/cbic.202000564 -
Drug Design, Development and Therapy 2022Several cases of small cell lung cancer (SCLC) patients demonstrate resistance to the treatment initiatives such as cisplatin after platinum chemotherapy. It is crucial...
AIM
Several cases of small cell lung cancer (SCLC) patients demonstrate resistance to the treatment initiatives such as cisplatin after platinum chemotherapy. It is crucial to the improvement of the overall survival (OS) of SCLC patients to discover the gene mutation inducing platinum resistance within this cohort.
PATIENTS AND METHODS
We analyzed the gene mutations significantly associated with the OS from 2 cohorts of SCLC platinum-treated patients. And then we screened out THSD7B mutation. In order to understand the mechanism between THSD7B mutation and platinum resistance, we designed gene mutation co-occurrence and mutual exclusivity analysis, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis, and Connectivity Map (CMap) analysis.
RESULTS
The poor prognosis of THSD7B mutant patients may be related to the inhibition of cell death-related pathways, the up-regulation of cell invasion and metastasis pathways, and the down-regulation of immune response pathways. Lovastatin and cyclooxygenase inhibitors could be used as potential target compounds in THSD7B mutant patients, which provides reference for future research on platinum resistance.
CONCLUSION
THSD7B can be considered a reliable biomarker that effectively facilitates the prediction of poor survival in SCLC platinum-treated patients.
Topics: Cisplatin; Humans; Lung Neoplasms; Mutation; Platinum; Small Cell Lung Carcinoma
PubMed: 35685767
DOI: 10.2147/DDDT.S363665 -
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