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Asian Pacific Journal of Cancer... May 2018Background: Triple-negative breast cancer (TNBC) is a sub-group of breast cancers with a particularly poor prognosis. The results of studies investigating the role of... (Meta-Analysis)
Meta-Analysis Review
Background: Triple-negative breast cancer (TNBC) is a sub-group of breast cancers with a particularly poor prognosis. The results of studies investigating the role of platinum-based chemotherapy (PBC) in metastatic TNBC (mTNBC) have been conflicting. In this meta-analysis, our aim was to assess the effectiveness of PBCs for mTNBCs. Methods: The PubMed, Cochrane Controlled Trials Register Databases, and EBSCOhost databases were accessed. The English language was used as the search language and only human studies were included. The Newcastle–Ottawa Quality Assessment Scale and the Jadad scoring system were used to evaluate the quality of the included randomized controlled studies. Results: Seven studies and 1,571 patients were included in this meta-analysis. The pooled hazard ratio (HR) for overall survival (OS), evaluated on the basis of six studies, showed the use of PBC regimes to be related to OS in mTNBCs (HR 0.620; 95% CI 0.513-0.749; p:<0.001). Four studies containing HR and abstract statistics used for HR calculation were included in the meta-analysis for progression-free survival (PFS). The pooled HR again indicated a significant relation (HR, 0.628; 95% CI, 0.501-0.786; p:<0.001). Conclusions: In this meta-analysis, we confirmed that PBC regimes provide OS and PFS advantages compared to non-PBC regimes. The use of PBC regimes could be a good choice in mTNBC patients for better quality of life and survival.
Topics: Female; Humans; Platinum; Prognosis; Triple Negative Breast Neoplasms
PubMed: 29801396
DOI: 10.22034/APJCP.2018.19.5.1169 -
International Archives of Occupational... Jul 2023The handling of antineoplastic drugs represents an occupational health risk for employees in pharmacies. To minimize exposure and to evaluate cleaning efficacy, wipe...
PURPOSE
The handling of antineoplastic drugs represents an occupational health risk for employees in pharmacies. To minimize exposure and to evaluate cleaning efficacy, wipe sampling was used to analyze antineoplastic drugs on surfaces. In 2009, guidance values were suggested to facilitate the interpretation of results, leading to a decrease in surface contamination. The goal of this follow-up was to evaluate the time trend of surface contamination, to identify critical antineoplastic drugs and sampling locations and to reassess guidance values.
METHODS
Platinum, 5-fluorouracil, cyclophosphamide, ifosfamide, gemcitabine, methotrexate, docetaxel and paclitaxel were analyzed in more than 17,000 wipe samples from 2000 to 2021. Statistical analysis was performed to describe and interpret the data.
RESULTS
Surface contaminations were generally relatively low. The median concentration for most antineoplastic drugs was below the limit of detection except for platinum (0.3 pg/cm). Only platinum and 5-fluorouracil showed decreasing levels over time. Most exceedances of guidance values were observed for platinum (26.9%), cyclophosphamide (18.5%) and gemcitabine (16.6%). The most affected wipe sampling locations were isolators (24.4%), storage areas (17.6%) and laminar flow hoods (16.6%). However, areas with no direct contact to antineoplastic drugs were also frequently contaminated (8.9%).
CONCLUSION
Overall, the surface contaminations with antineoplastic drugs continue to decrease or were generally at a low level. Therefore, we adjusted guidance values according to the available data. The identification of critical sampling locations may help pharmacies to further improve cleaning procedure and reduce the risk of occupational exposure to antineoplastic drugs.
Topics: Humans; Pharmacies; Platinum; Environmental Monitoring; Equipment Contamination; Antineoplastic Agents; Fluorouracil; Cyclophosphamide; Gemcitabine; Occupational Exposure
PubMed: 36877242
DOI: 10.1007/s00420-023-01963-y -
Journal of the American Chemical Society Dec 2021The Pt(IV) prodrug -[Pt(pyridine)(N)(OH)] () and its coumarin derivative -[Pt(pyridine)(N)(OH)(coumarin-3-carboxylate)] () are promising agents for photoactivated...
The Pt(IV) prodrug -[Pt(pyridine)(N)(OH)] () and its coumarin derivative -[Pt(pyridine)(N)(OH)(coumarin-3-carboxylate)] () are promising agents for photoactivated chemotherapy. These complexes are inert in the dark but release Pt(II) species and radicals upon visible light irradiation, resulting in photocytotoxicity toward cancer cells. Here, we have used synchrotron techniques to investigate the in-cell behavior of these prodrugs and visualize, for the first time, changes in cellular morphology and Pt localization upon treatment with and without light irradiation. We show that photoactivation of induces remarkable cellular damage with extreme alterations to multiple cellular components, including formation of vacuoles, while also significantly increasing the cellular accumulation of Pt species compared to dark conditions. X-ray absorption near-edge structure XANES) measurements in cells treated with indicate only partial reduction of the prodrug upon irradiation, highlighting that phototoxicity in cancer cells may involve not only Pt(II) photoproducts but also photoexcited Pt(IV) species.
Topics: Antineoplastic Agents; Cell Proliferation; Coordination Complexes; Humans; Light; PC-3 Cells; Platinum; Prodrugs; Single-Cell Analysis
PubMed: 34808054
DOI: 10.1021/jacs.1c08630 -
PloS One 2021This paper describes a detailed study of spectral and time-resolved photoprocesses in human platelets and their complexes with platinum (Pt) nanoparticles (NPs)....
This paper describes a detailed study of spectral and time-resolved photoprocesses in human platelets and their complexes with platinum (Pt) nanoparticles (NPs). Fluorescence, quantum yield, and platelet amino acid lifetime changes in the presence and without femtosecond ablated platinum NPs have been studied. Fluorescence spectroscopy analysis of main fluorescent amino acids and their residues (tyrosine (Tyr), tryptophan (Trp), and phenylalanine (Phe)) belonging to the platelet membrane have been performed. The possibility of energy transfer between Pt NPs and the platelet membrane has been revealed. Förster Resonance Energy Transfer (FRET) model was used to perform the quantitative evaluation of energy transfer parameters. The prospects of Pt NPs usage deals with quenching-based sensing for pathology's based on platelet conformations as cardiovascular diseases have been demonstrated.
Topics: Adult; Blood Platelets; Energy Transfer; Fluorescence Resonance Energy Transfer; Healthy Volunteers; Humans; Metal Nanoparticles; Platinum; Spectrometry, Fluorescence
PubMed: 34469464
DOI: 10.1371/journal.pone.0256621 -
BMC Medicine Aug 2020Ovarian cancer causes 151,900 deaths per year worldwide. Treatment and prognosis are primarily determined by the histopathologic interpretation in combination with...
BACKGROUND
Ovarian cancer causes 151,900 deaths per year worldwide. Treatment and prognosis are primarily determined by the histopathologic interpretation in combination with molecular diagnosis. However, the relationship between histopathology patterns and molecular alterations is not fully understood, and it is difficult to predict patients' chemotherapy response using the known clinical and histological variables.
METHODS
We analyzed the whole-slide histopathology images, RNA-Seq, and proteomics data from 587 primary serous ovarian adenocarcinoma patients and developed a systematic algorithm to integrate histopathology and functional omics findings and to predict patients' response to platinum-based chemotherapy.
RESULTS
Our convolutional neural networks identified the cancerous regions with areas under the receiver operating characteristic curve (AUCs) > 0.95 and classified tumor grade with AUCs > 0.80. Functional omics analysis revealed that expression levels of proteins participated in innate immune responses and catabolic pathways are associated with tumor grade. Quantitative histopathology analysis successfully stratified patients with different response to platinum-based chemotherapy (P = 0.003).
CONCLUSIONS
These results indicated the potential clinical utility of quantitative histopathology evaluation in tumor cell detection and chemotherapy response prediction. The developed algorithm is easily extensible to other tumor types and treatment modalities.
Topics: Female; Humans; Middle Aged; Ovarian Neoplasms; Platinum; Prognosis
PubMed: 32807164
DOI: 10.1186/s12916-020-01684-w -
Journal of Oleo Science 2023For practical applications such as fuel cells, it is important to exploit electrocatalysis with high activity for methanol and glycerol oxidation. A platinum...
For practical applications such as fuel cells, it is important to exploit electrocatalysis with high activity for methanol and glycerol oxidation. A platinum nanostructured electrode (PtNPs) is modified by gold adatoms and is created by application of a square wave potential regime to a tantalum surface electrode. In nanostructured platinum, the structure and the surface properties are characterized by scanning electron microscopy (SEM), X-ray powder diffraction (XRD) and cyclic voltammetry (CV). In acid and alkaline media, the CV and Chronoamperometric (CA) are studied to investigate the catalytic activity of the PtNPs nanoparticles for the electrooxidation of methanol and glycerol. The prepared nanostructured platinum on a tantalum electrode was allowed to balance an open circuit with a 1.0×10 M solution containing an Au ion. Consequently, the proximity of the irreversibly adsorbed Au-adatoms on the already described Pt-nanostructured electrode. In acidic and alkaline solutions, the electrocatalytically activities toward methanol and glycerol oxidation were evaluated and is found to strongly on the surface of the gold-modified PtNPs. The PtNPs modified by Au electrode system used direct methanol fuel cell (DMFC) and direct glycerol fuel cell (DGFC). The DMFC and DGFC are much higher than in acid output in alkaline. Comparison of the i-E curves of nanostructure platinum electrode with that of a platinum nanostructure electrode modified by Au under similar conditions for the letter, the charge under the peak (i-E curve) in the oxidation region was higher. Furthermore, rough chronoamperometric measurements confirmed the results. The results of showed that the electrocatalytic properties of the nanostructured prepared surface were enhanced by the inclusion of gold adatoms with a variable extent of advancement. The current peak (I) and the current chronoamperometric (I) of glycerol oxidation on the PtNPs electrode modified by Au in acid media (130 mA/cm, 47 µA/cm) were higher than those of the bare PtNPs electrode and in alkaline media (171 mA/cm, 66 µA/cm). The stronger catalytic behavior in alkaline media of the Au-PtNP electrode indicates its promising use in alkaline direct alcohol cells.
Topics: Methanol; Glycerol; Platinum; Tantalum; Nanostructures; Electrodes; Gold
PubMed: 36878588
DOI: 10.5650/jos.ess22376 -
Genes Nov 2023The precise mechanism of resistance to anti-cancer drugs such as platinum drugs is not fully revealed. To reveal the mechanism of drug resistance, the molecular networks...
The precise mechanism of resistance to anti-cancer drugs such as platinum drugs is not fully revealed. To reveal the mechanism of drug resistance, the molecular networks of anti-cancer drugs such as cisplatin, carboplatin, oxaliplatin, and arsenic trioxide were analyzed in several types of cancers. Since diffuse-type stomach adenocarcinoma, which has epithelial-mesenchymal transition (EMT)-like characteristics, is more malignant than intestinal-type stomach adenocarcinoma, the gene expression and molecular networks in diffuse- and intestinal-type stomach adenocarcinomas were analyzed. Analysis of carboplatin revealed the causal network in diffuse large B-cell lymphoma. The upstream regulators of the molecular networks of cisplatin-treated lung adenocarcinoma included the anti-cancer drug trichostatin A (TSA), a histone deacetylase inhibitor. The upstream regulator analysis of cisplatin revealed an increase in FAS, BTG2, SESN1, and CDKN1A, and the involvement of the tumor microenvironment pathway. The molecular networks were predicted to interact with several microRNAs, which may contribute to the identification of new drug targets for drug-resistant cancer. Analysis of oxaliplatin, a platinum drug, revealed that the SPINK1 pancreatic cancer pathway is inactivated in ischemic cardiomyopathy. The study showed the importance of the molecular networks of anti-cancer drugs and tumor microenvironment in the treatment of cancer resistant to anti-cancer drugs.
Topics: Humans; Cisplatin; Carboplatin; Platinum; Oxaliplatin; MicroRNAs; Antineoplastic Agents; Adenocarcinoma; Tumor Microenvironment; Trypsin Inhibitor, Kazal Pancreatic; Immediate-Early Proteins; Tumor Suppressor Proteins
PubMed: 38003016
DOI: 10.3390/genes14112073 -
Technology in Cancer Research &... 2021Triple-negative breast cancer constitutes approximately 12%-17% of all breast cancer cases, and >33% of patients develop distant metastases. Systemic cytotoxic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Triple-negative breast cancer constitutes approximately 12%-17% of all breast cancer cases, and >33% of patients develop distant metastases. Systemic cytotoxic chemotherapy is the primary treatment for patients with metastatic triple-negative breast cancer; however, the role of first-line platinum-based chemotherapy in these patients remains controversial. This meta-analysis evaluated the efficacy and safety of platinum-based first-line chemotherapy for patients with metastatic triple-negative breast cancer.
METHODS
We systematically searched the PubMed, Embase, Cochrane, and Clinical Trials registry databases up to June 1, 2020 to identify randomized controlled trials that investigated platinum-based vs. first-line platinum-free chemotherapy in patients with metastatic triple-negative breast cancer. We used fixed and random effects models to calculate pooled hazard ratios and odds ratios with 95% confidence intervals for progression-free and overall survival, objective response rates, and grade 3 and 4 adverse events.
RESULTS
Four randomized controlled trials ( = 590 patients) were included. Platinum-based chemotherapy significantly increased the objective response rates from 43.1% to 62.7% (odds ratio 2.34, 95% confidence interval 1.66-3.28, < 0.001). Three randomized controlled trials ( = 414 patients) reported survival outcomes. Patients administered platinum-based regimens showed significantly longer progression-free survival (hazard ratio 0.55, 95% confidence interval 0.37-0.82, = 0.004) and a nonsignificant trend toward improved overall survival (hazard ratio 0.76, 95% confidence interval 0.57-1.00, = 0.05). Only 2 studies reported the rates of grade 3 and 4 adverse events; grade 3-4 thrombocytopenia was more commonly associated with platinum-based chemotherapy (odds ratio 7.54, 95% confidence interval 1.37-41.60, = 0.02) and grade 3-4 fatigue with platinum-free chemotherapy (odds ratio 0.23, 95% confidence interval 0.08-0.68, = 0.008).
CONCLUSIONS
First-line platinum-based chemotherapy was associated with significantly increased objective response rates, longer progression-free survival, and a nonsignificant trend toward improved overall survival in patients with metastatic triple-negative breast cancer at the high risk of grade 3-4 thrombocytopenia.
Topics: Antineoplastic Agents; Female; Humans; Platinum; Prognosis; Randomized Controlled Trials as Topic; Survival Rate; Triple Negative Breast Neoplasms
PubMed: 33977814
DOI: 10.1177/15330338211016369 -
International Journal of Molecular... Nov 2023The DNA origami method has revolutionized the field of DNA nanotechnology since its introduction. These nanostructures, with their customizable shape and size,...
The DNA origami method has revolutionized the field of DNA nanotechnology since its introduction. These nanostructures, with their customizable shape and size, addressability, nontoxicity, and capacity to carry bioactive molecules, are promising vehicles for therapeutic delivery. Different approaches have been developed for manipulating and folding DNA origami, resulting in compact lattice-based and wireframe designs. Platinum-based complexes, such as cisplatin and phenanthriplatin, have gained attention for their potential in cancer and antiviral treatments. Phenanthriplatin, in particular, has shown significant antitumor properties by binding to DNA at a single site and inhibiting transcription. The present work aims to study wireframe DNA origami nanostructures as possible carriers for platinum compounds in cancer therapy, employing both cisplatin and phenanthriplatin as model compounds. This research explores the assembly, platinum loading capacity, stability, and modulation of cytotoxicity in cancer cell lines. The findings indicate that nanomolar quantities of the ball-like origami nanostructure, obtained in the presence of phenanthriplatin and therefore loaded with that specific drug, reduced cell viability in MCF-7 (cisplatin-resistant breast adenocarcinoma cell line) to 33%, while being ineffective on the other tested cancer cell lines. The overall results provide valuable insights into using wireframe DNA origami as a highly stable possible carrier of Pt species for very long time-release purposes.
Topics: Humans; Female; Cisplatin; Platinum; Pharmaceutical Preparations; DNA; Nanostructures; Breast Neoplasms; Nucleic Acid Conformation
PubMed: 38069036
DOI: 10.3390/ijms242316715 -
Biomaterials Sep 2024Platinum (Pt) is the metal of choice for electrodes in implantable neural prostheses like the cochlear implants, deep brain stimulating devices, and brain-computer... (Review)
Review
Platinum (Pt) is the metal of choice for electrodes in implantable neural prostheses like the cochlear implants, deep brain stimulating devices, and brain-computer interfacing technologies. However, it is well known since the 1970s that Pt dissolution occurs with electrical stimulation. More recent clinical and in vivo studies have shown signs of corrosion in explanted electrode arrays and the presence of Pt-containing particulates in tissue samples. The process of degradation and release of metallic ions and particles can significantly impact on device performance. Moreover, the effects of Pt dissolution products on tissue health and function are still largely unknown. This is due to the highly complex chemistry underlying the dissolution process and the difficulty in decoupling electrical and chemical effects on biological responses. Understanding the mechanisms and effects of Pt dissolution proves challenging as the dissolution process can be influenced by electrical, chemical, physical, and biological factors, all of them highly variable between experimental settings. By evaluating comprehensive findings on Pt dissolution mechanisms reported in the fuel cell field, this review presents a critical analysis of the possible mechanisms that drive Pt dissolution in neural stimulation in vitro and in vivo. Stimulation parameters, such as aggregate charge, charge density, and electrochemical potential can all impact the levels of dissolved Pt. However, chemical factors such as electrolyte types, dissolved gases, and pH can all influence dissolution, confounding the findings of in vitro studies with multiple variables. Biological factors, such as proteins, have been documented to exhibit a mitigating effect on the dissolution process. Other biological factors like cells and fibro-proliferative responses, such as fibrosis and gliosis, impact on electrode properties and are suspected to impact on Pt dissolution. However, the relationship between electrical properties of stimulating electrodes and Pt dissolution remains contentious. Host responses to Pt degradation products are also controversial due to the unknown chemistry of Pt compounds formed and the lack of understanding of Pt distribution in clinical scenarios. The cytotoxicity of Pt produced via electrical stimulation appears similar to Pt-based compounds, including hexachloroplatinates and chemotherapeutic agents like cisplatin. While the levels of Pt produced under clinical and acute stimulation regimes were typically an order of magnitude lower than toxic concentrations observed in vitro, further research is needed to accurately assess the mass balance and type of Pt produced during long-term stimulation and its impact on tissue response. Finally, approaches to mitigating the dissolution process are reviewed. A wide variety of approaches, including stimulation strategies, coating electrode materials, and surface modification techniques to avoid excess charge during stimulation and minimise tissue response, may ultimately support long-term and safe operation of neural stimulating devices.
Topics: Platinum; Humans; Animals; Electrodes, Implanted; Electric Stimulation; Electrochemistry; Electrodes
PubMed: 38677220
DOI: 10.1016/j.biomaterials.2024.122575