Flow Injection Analysis with Electrochemical Detection for Rapid Identification of Platinum-Based Cytostatics and Platinum Chlorides in Water

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Marketa Kominkova

2014-02-01

Full Text Available Platinum-based cytostatics, such as cisplatin, carboplatin or oxaliplatin are widely used agents in the treatment of various types of tumors. Large amounts of these drugs are excreted through the urine of patients into wastewaters in unmetabolised forms. This phenomenon leads to increased amounts of platinum ions in the water environment. The impacts of these pollutants on the water ecosystem are not sufficiently investigated as well as their content in water sources. In order to facilitate the detection of various types of platinum, we have developed a new, rapid, screening flow injection analysis method with electrochemical detection (FIA-ED. Our method, based on monitoring of the changes in electrochemical behavior of analytes, maintained by various pH buffers (Britton-Robinson and phosphate buffer and potential changes (1,000, 1,100 and 1,200 mV offers rapid and cheap selective determination of platinum-based cytostatics and platinum chlorides, which can also be present as contaminants in water environments.

Hormetic Effect of Berberine Attenuates the Anticancer Activity of Chemotherapeutic Agents.

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Jiaolin Bao

Full Text Available Hormesis is a phenomenon of biphasic dose response characterized by exhibiting stimulatory or beneficial effects at low doses and inhibitory or toxic effects at high doses. Increasing numbers of chemicals of various types have been shown to induce apparent hormetic effect on cancer cells. However, the underlying significance and mechanisms remain to be elucidated. Berberine, one of the major active components of Rhizoma coptidis, has been manifested with notable anticancer activities. This study aims to investigate the hormetic effect of berberine and its influence on the anticancer activities of chemotherapeutic agents. Our results demonstrated that berberine at low dose range (1.25 ~ 5 μM promoted cell proliferation to 112% ~170% of the untreated control in various cancer cells, while berberine at high dose rage (10 ~ 80 μM inhibited cell proliferation. Further, we observed that co-treatment with low dose berberine could significantly attenuate the anticancer activity of chemotherapeutic agents, including fluorouracil (5-FU, camptothecin (CPT, and paclitaxel (TAX. The hormetic effect and thereby the attenuated anticancer activity of chemotherapeutic drugs by berberine may attributable to the activated protective stress response in cancer cells triggered by berberine, as evidenced by up-regulated MAPK/ERK1/2 and PI3K/AKT signaling pathways. These results provided important information to understand the potential side effects of hormesis, and suggested cautious application of natural compounds and relevant herbs in adjuvant treatment of cancer.

Effect of the nitroimidazole Ro 03-8799 on the activity of chemotherapeutic agents against a murine tumour in vivo.

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Sheldon, P. W.; Gibson, P.

1984-01-01

The effect of the 2-nitroimidazole Ro 03-8799 (8799) on the activity of 11 chemotherapeutic agents against the anaplastic MT tumour in mice has been determined by soft agar cloning. The 8799, whilst producing little cytotoxicity by itself, potentiated the cytotoxic actions of the alkylating agents melphalan and cyclophosphamide, and the nitrosoureas BCNU, CCNU and MeCCNU. This potentiation was influenced by the time interval between the administration of 8799 and the chemotherapeutic agents, ...

Risk factors for the leakage of chemotherapeutic agents into systemic circulation after transcatheter arterial chemoembolization of hepatocellular carcinoma

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Ming-Yen Hsieh

2011-10-01

Full Text Available This prospective study was to investigate the possible risk factors for the leakage of chemotherapeutic agent into the systemic circulation after transcatheter arterial chemoembolization (TACE of hepatocellular carcinoma (HCC. Peripheral plasma concentrations of chemotherapeutic agents were determined at 1 hour and 72 hours after TACE by high-performance liquid chromatography in 53 patients. HCC were divided into three types namely single nodule (<5 cm, multiple nodules (all <5 cm, and main nodule measuring 5 cm or more. Forty-four patients (83% showed detectable chemotherapeutic concentrations within 72 hours after TACE. Patients with single nodular-type HCC had lower incidence of detectable plasma chemotherapeutic agents after TACE than the other two groups (all p<0.05. The injected doses of lipiodol, epirubicin, and mitomycin C were lower in patients without detection than in patients with detectable chemotherapeutic agents (all p<0.05. Multivariate logistic regression showed that tumor type and injected dose of lipiodol were two independent risk factors for the leakage of mitomycin C at 1 hour after TACE (all p<0.05, and the injected dose of mitomycin C was the risk factor for the leakage of epirubicin at 1 hour after TACE (p<0.05. In conclusion, multiple nodular type and large nodule measuring 5 cm or more have a risk of leakage of mitomycin C after TACE. Injected dose of lipiodol and mitomycin C as risk factor for the leakage of mitomycin C and epirubicin respectively may be because of competition of their injected volume within the limited space of target.

Hydrophilic nano-silica coating agents with platinum and diamond nanoparticles for denture base materials.

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Yoshizaki, Taro; Akiba, Norihisa; Inokoshi, Masanao; Shimada, Masayuki; Minakuchi, Shunsuke

2017-05-31

Preventing microorganisms from adhering to the denture surface is important for ensuring the systemic health of elderly denture wearers. Silica coating agents provide high hydrophilicity but lack durability. This study investigated solutions to improve the durability of the coating layer, determine an appropriate solid content concentration of SiO 2 in the silica coating agent, and evaluate the effect of adding platinum (Pt) and diamond nanoparticles (ND) to the agent. Five coating agents were prepared with different SiO 2 concentrations with/without Pt and ND additives. The contact angle was measured, and the brush-wear test was performed. Scanning electron microscopy was used to investigate the silica coating layer. The appropriate concentration of SiO 2 was found to be 0.5-0.75 wt%. The coating agents with additives showed significantly high hydrophilicity immediately after coating and after the brush-wear test. The coating agents with/without additives formed a durable coating layer even after the brush-wear test.

Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor

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Li X

2015-12-01

Full Text Available Xiaoyu Li, Meiying Wu, Limin Pan, Jianlin Shi State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, People’s Republic of China Abstract: To overcome the drawback of drug non-selectivity in traditional chemotherapy, the construction of multifunctional targeting drug delivery systems is one of the most effective and prevailing approaches. The intratumoral anti-angiogenesis and the tumor cell-killing are two basic approaches in fighting tumors. Herein we report a novel tumor vascular-targeting multidrug delivery system using mesoporous silica nanoparticles as carrier to co-load an antiangiogenic agent (combretastatin A4 and a chemotherapeutic drug (doxorubicin and conjugate with targeting molecules (iRGD peptide for combined anti-angiogenesis and chemotherapy. Such a dual-loaded drug delivery system is capable of delivering the two agents at tumor vasculature and then within tumors through a differentiated drug release strategy, which consequently results in greatly improved antitumor efficacy at a very low doxorubicin dose of 1.5 mg/kg. The fast release of the antiangiogenic agent at tumor vasculatures led to the disruption of vascular structure and had a synergetic effect with the chemotherapeutic drug slowly released in the following delivery of chemotherapeutic drug into tumors. Keywords: mesoporous silica nanoparticles, drug delivery, tumor vasculatures targeting, antiangiogenic agent

Hyperthermia and chemotherapy agent

International Nuclear Information System (INIS)

Roizin-Towle, L.; Hall, E.J.

1981-01-01

The use of chemotherapeutic agents for the treatment of cancer dates back to the late 19th century, but the modern era of chemotherapy drugs was ushered in during the 1940's with the development of the polyfunctional alkylating agent. Since then, numerous classes of drugs have evolved and the combined use of antineoplastic agents with other treatment modalities such as radiation or heat, remains a large relatively unexplored area. This approach, combining local hyperthermia with chemotherapy agents affords a measure of targeting and selective toxicity not previously available for drugs. In this paper, the effects of adriamycin, bleomycin and cis-platinum are examined. The adjuvant use of heat may also reverse the resistance of hypoxic cells noted for some chemotherapy agents

Current Research and Development of Chemotherapeutic Agents for Melanoma

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Kyaw Minn Hsan

2010-04-01

Full Text Available Cutaneous malignant melanoma is the most lethal form of skin cancer and an increasingly common disease worldwide. It remains one of the most treatment-refractory malignancies. The current treatment options for patients with metastatic melanoma are limited and in most cases non-curative. This review focuses on conventional chemotherapeutic drugs for melanoma treatment, by a single or combinational agent approach, but also summarizes some potential novel phytoagents discovered from dietary vegetables or traditional herbal medicines as alternative options or future medicine for melanoma prevention. We explore the mode of actions of these natural phytoagents against metastatic melanoma.

Determination of trace platinum by supramolecular catalytic kinetic spectrofluorimetry of {beta}-cyclodextrin-platinum-KBrO{sub 3}-salicylaldehyde furfuralhydrazone

Energy Technology Data Exchange (ETDEWEB)

Tang, Bo; Zhang, Ning; Chen, Zhen-Zhen; Kong, Qing-Cheng [Shandong Normal University, College of Chemistry, Chemical Engineering and Materials Science, Jinan (China)

2006-02-01

A supramolecular catalytic kinetic spectrofluorimetric method was developed for the determination of platinum(IV) and the possible mechanism of catalytic reaction was discussed. The method was based on the fluorescence-enhancing reaction of salicylaldehyde furfuralhydrazone (SAFH) with potassium bromate, which was catalysed by platinum(IV) in a water-ethanol medium. {beta}-Cyclodextrin ({beta}-CD) obviously sensitized the determination at pH 5.20 and 25 C. Under optimum conditions, the {beta}-CD-platinum-KBrO{sub 3}-SAFH supramolecular kinetic catalytic reaction system had excitation and emission maxima at 372 and 461 nm, respectively. The linear range of this method was 0.60-180 ng ml{sup -1} with a relative standard deviation of 1.2%, and the detection limit was 0.18 ng ml{sup -1}. Investigation of the mechanism and the effects of interferences is presented. The proposed method was applied successfully to determine trace platinum(IV) in the chemotherapeutic drug cisplatin and serum from patients with satisfactory results. (orig.)

PET studies of potential chemotherapeutic agents: Pt. 10

International Nuclear Information System (INIS)

Conway, T.; Diksic, M.; McGill Univ., Montreal, PQ

1991-01-01

Carbon-11-labeled HECNU [1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea] a potential chemotherapeutic agent, has been prepared by the nitrosation of the corresponding carbon-11-labeled urea, HECU, [1-(2-chloroethyl)-3-(2-hydroxyethyl) urea]. The isomeric byproduct of nitrosation, 1-(2-chloroethyl)-3-nitroso-3-(2-hydroxyethyl) urea can be efficiently removed by preparative scale HPLC on a Partisil column. ( 11 C)-HECU was prepared by reacting ethanolamine with ( 11 C)-2-chloroethyl-isocyanate which was itself prepared by reacting ( 11 C)-phosgene with 2-chloroethylamine hydrochloride suspended in dioxane at 60-65 o C. This synthesis yielded ( 11 C)-HECNU with an average radiochemical purity of 98% in an average radiochemical yield of 18% relative to the radioactivity measured at the end of the 11 C-phosgene introduction. (author)

TP53 status and taxane-platinum versus platinum-based therapy in ovarian cancer patients: A non-randomized retrospective study

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Markowska Janina

2008-01-01

Full Text Available Abstract Background Taxane-platinum therapy (TP has replaced platinum-based therapy (PC or PAC, DNA damaging chemotherapy in the postoperative treatment of ovarian cancer patients; however, it is not always effective. TP53 protein plays a differential role in response to DNA-damaging agents and taxanes. We sought to define profiles of patients who benefit the most from TP and also of those who can be treated with PC. Methods We compared the effectiveness of PC/PAC (n = 253 and TP (n = 199 with respect to tumor TP53 accumulation in ovarian cancer patients with FIGO stage IIB-IV disease; this was a non-randomized retrospective study. Immunohistochemical analysis was performed on 452 archival tumors; univariate and multivariate analysis by the Cox's and logistic regression models was performed in all patients and in subgroups with [TP53(+] and without TP53 accumulation [TP53(-]. Results The advantage of taxane-platinum therapy over platinum-based therapy was seen in the TP53(+, and not in the TP53(- group. In the TP53(+ group taxane-platinum therapy enhanced the probability of complete remission (p = .018, platinum sensitivity (p = .014, platinum highly sensitive response (p = .038 and longer survival (OS, p = .008. Poor tumor differentiation diminished the advantage from taxane-platinum therapy in the TP53(+ group. In the TP53(- group PC/PAC was at least equally efficient as taxane-platinum therapy and it enhanced the chance of platinum highly sensitive response (p = .010. However, in the TP53(- group taxane-platinum therapy possibly diminished the risk of death in patients over 53 yrs (p = .077. Among factors that positively interacted with taxane-platinum therapy in some analyses were endometrioid and clear cell type, FIGO III stage, bulky residual tumor, more advanced age of patient and moderate tumor differentiation. Conclusion Our results suggest that taxane-platinum therapy is particularly justified in patients with TP53(+ tumors or older

Activation of the human immune system by chemotherapeutic or targeted agents combined with the oncolytic parvovirus H-1

International Nuclear Information System (INIS)

Moehler, Markus; Sieben, Maike; Roth, Susanne; Springsguth, Franziska; Leuchs, Barbara; Zeidler, Maja; Dinsart, Christiane; Rommelaere, Jean; Galle, Peter R

2011-01-01

Parvovirus H-1 (H-1PV) infects and lyses human tumor cells including melanoma, hepatoma, gastric, colorectal, cervix and pancreatic cancers. We assessed whether the beneficial effects of chemotherapeutic agents or targeted agents could be combined with the oncolytic and immunostimmulatory properties of H-1PV. Using human ex vivo models we evaluated the biological and immunological effects of H-1PV-induced tumor cell lysis alone or in combination with chemotherapeutic or targeted agents in human melanoma cells +/- characterized human cytotoxic T-cells (CTL) and HLA-A2-restricted dendritic cells (DC). H-1PV-infected MZ7-Mel cells showed a clear reduction in cell viability of >50%, which appeared to occur primarily through apoptosis. This correlated with viral NS1 expression levels and was enhanced by combination with chemotherapeutic agents or sunitinib. Tumor cell preparations were phagocytosed by DC whose maturation was measured according to the treatment administered. Immature DC incubated with H-1PV-induced MZ7-Mel lysates significantly increased DC maturation compared with non-infected or necrotic MZ7-Mel cells. Tumor necrosis factor-α and interleukin-6 release was clearly increased by DC incubated with H-1PV-induced SK29-Mel tumor cell lysates (TCL) and was also high with DC-CTL co-cultures incubated with H-1PV-induced TCL. Similarly, DC co-cultures with TCL incubated with H-1PV combined with cytotoxic agents or sunitinib enhanced DC maturation to a greater extent than cytotoxic agents or sunitinib alone. Again, these combinations increased pro-inflammatory responses in DC-CTL co-cultures compared with chemotherapy or sunitinib alone. In our human models, chemotherapeutic or targeted agents did not only interfere with the pronounced immunomodulatory properties of H-1PV, but also reinforced drug-induced tumor cell killing. H-1PV combined with cisplatin, vincristine or sunitinib induced effective immunostimulation via a pronounced DC maturation, better cytokine

Measuring the Acoustic Release of a Chemotherapeutic Agent from Folate-Targeted Polymeric Micelles.

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Abusara, Ayah; Abdel-Hafez, Mamoun; Husseini, Ghaleb

2018-08-01

In this paper, we compare the use of Bayesian filters for the estimation of release and re-encapsulation rates of a chemotherapeutic agent (namely Doxorubicin) from nanocarriers in an acoustically activated drug release system. The study is implemented using an advanced kinetic model that takes into account cavitation events causing the antineoplastic agent's release from polymeric micelles upon exposure to ultrasound. This model is an improvement over the previous representations of acoustic release that used simple zero-, first- and second-order release and re-encapsulation kinetics to study acoustically triggered drug release from polymeric micelles. The new model incorporates drug release and micellar reassembly events caused by cavitation allowing for the controlled release of chemotherapeutics specially and temporally. Different Bayesian estimators are tested for this purpose including Kalman filters (KF), Extended Kalman filters (EKF), Particle filters (PF), and multi-model KF and EKF. Simulated and experimental results are used to verify the performance of the above-mentioned estimators. The proposed methods demonstrate the utility and high-accuracy of using estimation methods in modeling this drug delivery technique. The results show that, in both cases (linear and non-linear dynamics), the modeling errors are expensive but can be minimized using a multi-model approach. In addition, particle filters are more flexible filters that perform reasonably well compared to the other two filters. The study improved the accuracy of the kinetic models used to capture acoustically activated drug release from polymeric micelles, which may in turn help in designing hardware and software capable of precisely controlling the delivered amount of chemotherapeutics to cancerous tissue.

Status epilepticus associated with platinum chemotherapy in a patient with cervical cancer: a case report

International Nuclear Information System (INIS)

Holman, Laura L.; Ren, Yulan; Westin, Shannon N.

2015-01-01

While peripheral neuropathy is a common side effect of platinum-based chemotherapy, central nervous system (CNS) toxicity, such as encephalopathy or seizures, appears to be rare. This manuscript describes the only reported case of nonconvulsive status epilepticus associated with cisplatin in a cervical cancer patient who does not have other underlying medical conditions. The patient is a 54-year-old Chinese female with recurrent stage IIIB moderately differentiated squamous cell carcinoma of the cervix who was being treated with cisplatin and topotecan. During the sixth cycle of this regimen, the patient presented with mental status changes. While imaging and laboratory values were within normal limits, the patient’s EEG revealed nonconvulsive status epilepticus. After appropriate intervention, she made a complete recovery with no further seizures. The patient currently remains on antiepileptic therapy, but is no longer receiving cisplatin. Patients who present with new onset seizures should primarily be evaluated for underlying medical conditions. Among patients who are suspected to have CNS side effects associated with platinum use, we recommend avoidance of platinum agents in future chemotherapeutic regimens. Although rare, providers should be aware of the potential for CNS toxicity associated with this drug class

4-aminoquinoline analogues and its platinum (II) complexes as antimalarial agents.

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de Souza, Nicolli Bellotti; Carmo, Arturene M L; Lagatta, Davi C; Alves, Márcio José Martins; Fontes, Ana Paula Soares; Coimbra, Elaine Soares; da Silva, Adilson David; Abramo, Clarice

2011-07-01

The high incidence of malaria and drug-resistant strains of Plasmodium have turned this disease into a problem of major health importance. One of the approaches used to control it is to search for new antimalarial agents, such as quinoline derivates. This class of compounds composes a broad group of antimalarial agents, which are largely employed, and inhibits the formation of β-haematin (malaria pigment), which is lethal to the parasite. More specifically, 4-aminoquinoline derivates represent potential sources of antimalarials, as the example of chloroquine, the most used antimalarial worldwide. In order to assess antimalarial activity, 12 4-aminoquinoline derived drugs were obtained and some of these derivatives were used to obtain platinum complexes platinum (II). These compounds were tested in vivo in a murine model and revealed remarkable inhibition of parasite multiplication values, whose majority ranged from 50 to 80%. In addition they were not cytotoxic. Thus, they may be object of further research for new antimalarial agents. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Using a device for continuous infusion of a chemotherapeutic agent in the perception of the oncologic patient

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Julianna de Freitas Siqueira

2014-01-01

Full Text Available This is a qualitative study whose aim was to describe the perception of an oncologic patient regarding the use of a device for continuous infusion of a chemotherapeutic agent. It was carried out with eight patients, through a semi-structured interview with this guiding question: “How do you feel about using a device for continuous infusion of a chemotherapeutic agent?”. Three categories emerged: avoiding hospitalization; unveiling the unknown; and performing activities. The patient highlights the benefit of going home and the possibility of performing activities, despite the anxiety regarding the presence of the device and the new experience in her/his daily life. The results were important to direct the guidelines related to the positive and negative aspects of this technology.

New Insights into the Mechanism Underlying the Synergistic Action of Ionizing Radiation With Platinum Chemotherapeutic Drugs: The Role of Low-Energy Electrons

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Rezaee, Mohammad, E-mail: Mohammad.Rezaee@USherbrooke.ca; Hunting, Darel John; Sanche, Léon

2013-11-15

Purpose: To investigate the efficiencies of platinum chemotherapeutic drugs (Pt-drugs) in the sensitization of DNA to the direct effects of ionizing radiation and to determine the role of low-energy electrons (LEEs) in this process. Methods and Materials: Complexes of supercoiled plasmid DNA covalently bound to either cisplatin, carboplatin, or oxaliplatin were prepared in different molar ratios. Solid films of DNA and DNA modified by Pt-drugs were irradiated with either 10-KeV or 10-eV electrons. Damages to DNA were quantified by gel electrophoresis, and the yields for damage formation were obtained from exposure–response curves. Results: The presence of an average of 2 Pt-drug–DNA adducts (Pt-adducts) in 3199-bp plasmid DNA increases the probability of a double-strand break by factors of 3.1, 2.5, and 2.4 for carboplatin, cisplatin, and oxaliplatin, respectively. Electrons with energies of 10 eV and 10 KeV interact with Pt-adducts to preferentially enhance the formation of cluster lesions. The maximum increase in radiosensitivity per Pt-adduct is found at ratios up to 3.1 × 10{sup −4} Pt-adducts per nucleotide, which is equivalent to an average of 2 adducts per plasmid. Carboplatin and oxaliplatin show higher efficiencies than cisplatin in the radiosensitization of DNA. Because carboplatin and cisplatin give rise to identical reactive species that attach to DNA, carboplatin must be considered as a better radiosensitizer for equal numbers of Pt-adducts. Conclusion: Platinum chemotherapeutic drugs preferentially enhance the formation of cluster damage to DNA induced by the direct effect of ionizing radiation, and LEEs are the main species responsible for such an enhancement via the formation of electron resonances.

New Insights into the Mechanism Underlying the Synergistic Action of Ionizing Radiation With Platinum Chemotherapeutic Drugs: The Role of Low-Energy Electrons

International Nuclear Information System (INIS)

Rezaee, Mohammad; Hunting, Darel John; Sanche, Léon

2013-01-01

Purpose: To investigate the efficiencies of platinum chemotherapeutic drugs (Pt-drugs) in the sensitization of DNA to the direct effects of ionizing radiation and to determine the role of low-energy electrons (LEEs) in this process. Methods and Materials: Complexes of supercoiled plasmid DNA covalently bound to either cisplatin, carboplatin, or oxaliplatin were prepared in different molar ratios. Solid films of DNA and DNA modified by Pt-drugs were irradiated with either 10-KeV or 10-eV electrons. Damages to DNA were quantified by gel electrophoresis, and the yields for damage formation were obtained from exposure–response curves. Results: The presence of an average of 2 Pt-drug–DNA adducts (Pt-adducts) in 3199-bp plasmid DNA increases the probability of a double-strand break by factors of 3.1, 2.5, and 2.4 for carboplatin, cisplatin, and oxaliplatin, respectively. Electrons with energies of 10 eV and 10 KeV interact with Pt-adducts to preferentially enhance the formation of cluster lesions. The maximum increase in radiosensitivity per Pt-adduct is found at ratios up to 3.1 × 10 −4 Pt-adducts per nucleotide, which is equivalent to an average of 2 adducts per plasmid. Carboplatin and oxaliplatin show higher efficiencies than cisplatin in the radiosensitization of DNA. Because carboplatin and cisplatin give rise to identical reactive species that attach to DNA, carboplatin must be considered as a better radiosensitizer for equal numbers of Pt-adducts. Conclusion: Platinum chemotherapeutic drugs preferentially enhance the formation of cluster damage to DNA induced by the direct effect of ionizing radiation, and LEEs are the main species responsible for such an enhancement via the formation of electron resonances

African indigenous plants with chemotherapeutic potentials and ...

African Journals Online (AJOL)

Herbal-based and plant-derived products can be exploited with sustainable comparative and competitive advantage. This review presents some indigenous African plants with chemotherapeutic properties and possible ways of developing them into potent pharmacological agents using biotechnological approaches.

Polymeric Micelles with Ionic Cores Containing Biodegradable Crosslinks for Delivery of Chemotherapeutic Agents

OpenAIRE

Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V.; Bronich, Tatiana K.

2010-01-01

Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca2+) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like n...

Lung Damage due to Chemotherapeutic Agents

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Serdar Kalemci

2014-12-01

Full Text Available Chemotherapeutic drug-induced pulmonary toxicity not only emerges in cumulative doses, but also can be observed even at low dosages. Combined administration of many drugs, concurrent radiotherapy applications, opportunistic infections, lymphangitic tumor extension and pleural metastases complicate the disease diagnosis.

The chemotherapeutic agent paclitaxel selectively impairs learning while sparing source memory and spatial memory.

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Smith, Alexandra E; Slivicki, Richard A; Hohmann, Andrea G; Crystal, Jonathon D

2017-03-01

Chemotherapeutic agents are widely used to treat patients with systemic cancer. The efficacy of these therapies is undermined by their adverse side-effect profiles such as cognitive deficits that have a negative impact on the quality of life of cancer survivors. Cognitive side effects occur across a variety of domains, including memory, executive function, and processing speed. Such impairments are exacerbated under cognitive challenges and a subgroup of patients experience long-term impairments. Episodic memory in rats can be examined using a source memory task. In the current study, rats received paclitaxel, a taxane-derived chemotherapeutic agent, and learning and memory functioning was examined using the source memory task. Treatment with paclitaxel did not impair spatial and episodic memory, and paclitaxel treated rats were not more susceptible to cognitive challenges. Under conditions in which memory was not impaired, paclitaxel treatment impaired learning of new rules, documenting a decreased sensitivity to changes in experimental contingencies. These findings provide new information on the nature of cancer chemotherapy-induced cognitive impairments, particularly regarding the incongruent vulnerability of episodic memory and new learning following treatment with paclitaxel. Copyright © 2016 Elsevier B.V. All rights reserved.

Interaction of Classical Platinum Agents with the Monomeric and Dimeric Atox1 Proteins: A Molecular Dynamics Simulation Study

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Xiaolei Wang

2013-12-01

Full Text Available We carried out molecular dynamics simulations and free energy calculations for a series of binary and ternary models of the cisplatin, transplatin and oxaliplatin agents binding to a monomeric Atox1 protein and a dimeric Atox1 protein to investigate their interaction mechanisms. All three platinum agents could respectively combine with the monomeric Atox1 protein and the dimeric Atox1 protein to form a stable binary and ternary complex due to the covalent interaction of the platinum center with the Atox1 protein. The results suggested that the extra interaction from the oxaliplatin ligand–Atox1 protein interface increases its affinity only for the OxaliPt + Atox1 model. The binding of the oxaliplatin agent to the Atox1 protein might cause larger deformation of the protein than those of the cisplatin and transplatin agents due to the larger size of the oxaliplatin ligand. However, the extra interactions to facilitate the stabilities of the ternary CisPt + 2Atox1 and OxaliPt + 2Atox1 models come from the α1 helices and α2-β4 loops of the Atox1 protein–Atox1 protein interface due to the cis conformation of the platinum agents. The combinations of two Atox1 proteins in an asymmetric way in the three ternary models were analyzed. These investigations might provide detailed information for understanding the interaction mechanism of the platinum agents binding to the Atox1 protein in the cytoplasm.

Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

Energy Technology Data Exchange (ETDEWEB)

Thys, Ryan G., E-mail: rthys@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Lehman, Christine E., E-mail: clehman@wakehealth.edu [Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1016 (United States); Pierce, Levi C.T., E-mail: Levipierce@gmail.com [Human Longevity, Inc., San Diego, California 92121 (United States); Wang, Yuh-Hwa, E-mail: yw4b@virginia.edu [Department of Biochemistry and Molecular Genetics, University of Virginia, 1340 Jefferson Park Avenue, Charlottesville, VA 22908-0733 (United States)

2015-09-15

Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

Environmental and chemotherapeutic agents induce breakage at genes involved in leukemia-causing gene rearrangements in human hematopoietic stem/progenitor cells

International Nuclear Information System (INIS)

Thys, Ryan G.; Lehman, Christine E.; Pierce, Levi C.T.; Wang, Yuh-Hwa

2015-01-01

Highlights: • Environmental/chemotherapeutic agents cause DNA breakage in MLL and CBFB in HSPCs. • Diethylnitrosamine-induced DNA breakage at MLL and CBFB shown for the first time. • Chemical-induced DNA breakage occurs at topoisomerase II cleavage sites. • Chemical-induced DNA breaks display a pattern similar to those in leukemia patients. • Long-term exposures suggested to generate DNA breakage at leukemia-related genes. - Abstract: Hematopoietic stem and progenitor cells (HSPCs) give rise to all of the cells that make up the hematopoietic system in the human body, making their stability and resilience especially important. Damage to these cells can severely impact cell development and has the potential to cause diseases, such as leukemia. Leukemia-causing chromosomal rearrangements have largely been studied in the context of radiation exposure and are formed by a multi-step process, including an initial DNA breakage and fusion of the free DNA ends. However, the mechanism for DNA breakage in patients without previous radiation exposure is unclear. Here, we investigate the role of non-cytotoxic levels of environmental factors, benzene, and diethylnitrosamine (DEN), and chemotherapeutic agents, etoposide, and doxorubicin, in generating DNA breakage at the patient breakpoint hotspots of the MLL and CBFB genes in human HSPCs. These conditions represent exposure to chemicals encountered daily or residual doses from chemotherapeutic drugs. Exposure of HSPCs to non-cytotoxic levels of environmental chemicals or chemotherapeutic agents causes DNA breakage at preferential sites in the human genome, including the leukemia-related genes MLL and CBFB. Though benzene, etoposide, and doxorubicin have previously been linked to leukemia formation, this is the first study to demonstrate a role for DEN in the generation of DNA breakage at leukemia-specific sites. These chemical-induced DNA breakpoints coincide with sites of predicted topoisomerase II cleavage. The

Synthesis, structural characterization, and pro-apoptotic activity of 1-indanone thiosemicarbazone platinum(II) and palladium(II) complexes: potential as antileukemic agents.

Science.gov (United States)

Gómez, Natalia; Santos, Diego; Vázquez, Ramiro; Suescun, Leopoldo; Mombrú, Alvaro; Vermeulen, Monica; Finkielsztein, Liliana; Shayo, Carina; Moglioni, Albertina; Gambino, Dinorah; Davio, Carlos

2011-08-01

In the search for alternative chemotherapeutic strategies against leukemia, various 1-indanone thiosemicarbazones, as well as eight novel platinum(II) and palladium(II) complexes, with the formula [MCl₂(HL)] and [M(HL)(L)]Cl, derived from two 1-indanone thiosemicarbazones were synthesized and tested for antiproliferative activity against the human leukemia U937 cell line. The crystal structure of [Pt(HL1)(L1)]Cl·2MeOH, where L1=1-indanone thiosemicarbazone, was solved by X-ray diffraction. Free thiosemicarbazone ligands showed no antiproliferative effect, but the corresponding platinum(II) and palladium(II) complexes inhibited cell proliferation and induced apoptosis. Platinum(II) complexes also displayed selective apoptotic activity in U937 cells but not in peripheral blood monocytes or the human hepatocellular carcinoma HepG2 cell line used to screen for potential hepatotoxicity. Present findings show that, in U937 cells, 1-indanone thiosemicarbazones coordinated to palladium(II) were more cytotoxic than those complexed with platinum(II), although the latter were found to be more selective for leukemic cells suggesting that they are promising compounds with potential therapeutic application against hematological malignancies. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Platinum(II)-gadolinium(III) complexes as potential single-molecular theranostic agents for cancer treatment.

Science.gov (United States)

Zhu, Zhenzhu; Wang, Xiaoyong; Li, Tuanjie; Aime, Silvio; Sadler, Peter J; Guo, Zijian

2014-11-24

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)-gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt-Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd-DTPA. T1-weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt-Gd complexes promising theranostic agents for cancer treatment. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vitro sensitivity of Trichomonas vaginalis and Candida albicans to chemotherapeutic agents.

Science.gov (United States)

Lövgren, T; Salmela, I

1978-06-01

Strains of fresh clinical isolates of Trichomonas vaginalis and Candida albicans have been tested in vitro for their sensitivity to eight drugs used in the therapy of monilial and trichomonal vaginitis. Three of the chemotherapeutic agents, chlorchinaldol, clotrimazole and broxyquinoline were effective against both organisms. Tinidazole and metronidazole were active against T. vaginalis. The strains of C. albicans were also sensitive to trichomycin, natamycin and nystatin. Tinidazole was the most effective trichomonacide, clotrimazole and chlorchinaldol were most effective against C. albicans, while chlorchinaldol had the best in vitro effect against both organisms. The ranges of the MICs are compared to values previously reported.

1,3-Bis(2-chloroethyl)-1-nitrosourea-loaded bovine serum albumin nanoparticles with dual magnetic resonance-fluorescence imaging for tracking of chemotherapeutic agents.

Science.gov (United States)

Wei, Kuo-Chen; Lin, Feng-Wei; Huang, Chiung-Yin; Ma, Chen-Chi M; Chen, Ju-Yu; Feng, Li-Ying; Yang, Hung-Wei

To date, knowing how to identify the location of chemotherapeutic agents in the human body after injection is still a challenge. Therefore, it is urgent to develop a drug delivery system with molecular imaging tracking ability to accurately understand the distribution, location, and concentration of a drug in living organisms. In this study, we developed bovine serum albumin (BSA)-based nanoparticles (NPs) with dual magnetic resonance (MR) and fluorescence imaging modalities (fluorescein isothiocyanate [FITC]-BSA-Gd/1,3-bis(2-chloroethyl)-1-nitrosourea [BCNU] NPs) to deliver BCNU for inhibition of brain tumor cells (MBR 261-2). These BSA-based NPs are water dispersible, stable, and biocompatible as confirmed by XTT cell viability assay. In vitro phantoms and in vivo MR and fluorescence imaging experiments show that the developed FITC-BSA-Gd/BCNU NPs enable dual MR and fluorescence imaging for monitoring cellular uptake and distribution in tumors. The T1 relaxivity (R1) of FITC-BSA-Gd/BCNU NPs was 3.25 mM(-1) s(-1), which was similar to that of the commercial T1 contrast agent (R1 =3.36 mM(-1) s(-1)). The results indicate that this multifunctional drug delivery system has potential bioimaging tracking of chemotherapeutic agents ability in vitro and in vivo for cancer therapy.

Oxaliplatin-induced neuropathy in colorectal cancer

DEFF Research Database (Denmark)

Zedan, Ahmed; Hansen, Torben Frøstrup; Fex Svenningsen, Åsa

2014-01-01

Oxaliplatin is a chemotherapeutic agent effective against advanced colorectal cancer. Unlike with other platinum-based agents, the main side effect of oxaliplatin is polyneuropathy. Oxaliplatin-induced polyneuropathy (OIPN) has a unique profile, which can be divided into acute and chronic...

Chemotherapeutic targets in parasites: contemporary strategies

National Research Council Canada - National Science Library

Mansour, Tag E; Mansour, Joan MacKinnon

2002-01-01

... identify effective antiparasitic agents. An introduction to the early development of parasite chemotherapy is followed by an overview of biophysical techniques and genomic and proteomic analyses. Several chapters are devoted to specific types of chemotherapeutic agents and their targets in malaria, trypanosomes, leishmania, and amitochondrial...

Neutron activation analysis in trace element determinaton in studies of wound healing and in the framework of dose-effect studies on platinum-containing cancer chemotherapeutics

International Nuclear Information System (INIS)

Trebert Haeberlin, S.

1986-01-01

The origin of the iron concentration in wound tissues was studied. To differentiate between blood and tissue iron the erythrocytes of a rabbit were marked with radioactive 55 Fe. Under the assumption that the half-life of rabbit erythrocytes of 34.5 days would not be changed by 55 Fe marking, the 55 Fe activity found in samples taken from the wound area of muscle cut wounds in a healing time of up to 14 days should be a measure for the blood iron share in the wound. The total iron content was determined be measuring 59 Fe with the help of NAA. The portion of iron which was from the tissues was found as the difference between total iron (NAA) and blood iron ( 55 Fe). The activation analysis of the samples from the wound tissues was supposed to give information about the participation of other essential trace elements in wound healing. In the framework of the development of new cancer chemotherapeutics with a specific effect on hormone-dependent mammary carcinoma, the distribution of the respective medications in tumor tissues and organs of rats and mice based on the activation analysis determination of platinum content in tissues of interest was ascertained. In the activation analyses for platinum determination the amounts in the samples of other essential trace elements was also determined, in order to ascertain characteristic accumulation or reduction of trace elements in various tissues as a result of tumor development or in connection with therapy. (orig./MG) [de

Combined Effects of Fe3O4 Nanoparticles and Chemotherapeutic Agents on Prostate Cancer Cells In Vitro

Directory of Open Access Journals (Sweden)

Kanako Kojima

2018-01-01

Full Text Available Patients with metastatic castration-resistant prostate cancer (mCRPC have poor outcomes. Docetaxel (DTX-based therapy is a current standard treatment for patients with mCRPC. Approaches combining conventional chemotherapeutic agents and nanoparticles (NPs, particularly iron oxide NPs, may overcome the serious side effects and drug resistance, resulting in the establishment of new therapeutic strategies. We previously reported the combined effects of Fe3O4 nanoparticles (Fe3O4 NPs with DTX on prostate cancer cells in vitro. In this study, we investigated the combined effects of Fe3O4 NPs and rapamycin or carboplatin on prostate cancer cells in vitro. Treatment of DU145 and PC-3 cells with Fe3O4 NPs increased intracellular reactive oxygen species (ROS levels in a concentration-dependent manner. Treatment of both cell lines with 100 μg/mL Fe3O4 NPs for 72 h resulted in significant inhibition of cell viability with a different inhibitory effect. Combination treatments with 100 µg/mL Fe3O4 NPs and 10 µM carboplatin or 10 nM rapamycin in DU145 and PC-3 cells significantly decreased cell viability. Synergistic effects on apoptosis were observed in PC-3 cells treated with Fe3O4 NPs and rapamycin and in DU145 cells with Fe3O4 NPs and carboplatin. These results suggest the possibility of combination therapy with Fe3O4 NPs and various chemotherapeutic agents as a novel therapeutic strategy for patients with mCRPC.

Pyrimidine nucleoside analogues, potential chemotherapeutic agents, and substrates/inhibitors in various enzyme systems

International Nuclear Information System (INIS)

Kulikowski, T.; Bretner, M.; Felczak, K.; Drabikowska, A.; Shugar, D.

1998-01-01

Full text. Pyrimidine nucleoside analogues are an important class of compounds with antimetabolic (antitumor, antiparasitic and antiviral) properties. The synthesis of thiated nucleoside and nucleotide analogues, determination of structures, conformation and dissociation constans, their potential chemotherapeutic activities, and their substrate/inhibitor properties in various enzyme systems, with emphasis on enzymes related to chemotherapeutic activities, were investigated. In the series of thionated inhibitors of thymidylate synthase (TS), potential antitumor agents, regioselective syntheses were elaborated for 2- and 4-thio, and 2,4-dithio derivatives of 2'-deoxyuridine (dUrd), 5-fluoro-2'-deoxyuridine (FdUrd), and several other 5-fluoro-, 5-bromo- and 5-trifluoromethyl congeners, and the 2-thio derivatives of FdUrd and its α-anomer, which proved to be selective agents with high cytotoxicities correlated with the inhibitory activities vs TS of their corresponding 5'-monophosphates. Regioslective syntheses were also elaborated for 2'-deoxycytidin e and 5-fluoro-2'-deoxycitidine derivatives. Solution conformation of these nucleosides were deduced from high-resolution (500 MHz) 1 H NMR spectra. Substrate/inhibitor properties of 2-thio-2'-deoxycitidine (S 2 dCyd) and 5-fluoro-2-thio-2'-deoxycitidine ( S 2 FdCyd) with respect to human leukemic spleen deoxycytidine kinase have been examined. Both are substrates, and also good inhibitors, of phosphorylation of 2'-deoxycitidine and 2'-deoxyadenosine. Particular attention was directed to the specificity of t he NTP phosphate donor for several nucleoside kinases, and procedures have been developed for distinguishing between ATP and other NTP donors, a problem of importance in chemotherapy with nucleoside analogues. Biological properties of the newly synthetize d thiated pyrimidine 2',3'-dideoxy-3'-fluoronucleosides, S 2 ,3'-FddUrd and S 2 ,3'-FddThd, were also investigated. Thiated 3'-fluoronucleosides were moderate

The safety of antiangiogenic agents and PARP inhibitors in platinum-sensitive recurrent ovarian cancer.

Science.gov (United States)

Lorusso, Domenica; Fontanella, Caterina; Maltese, Giuseppa; Lepori, Stefano; Tripodi, Elisa; Bogani, Giorgio; Raspagliesi, Francesco

2017-06-01

Recurrence is a common event in endothelial ovarian cancer (EOC) patients, and the choice of the most appropriate treatment is driven by the platinum-free interval, molecular characteristics of the disease such as BRCA mutational status, previous treatments and toxicity. Areas covered: This review focuses on the main hematologic and non-hematologic toxicities correlated with the use of licensed antiangiogenic agents and PARP inhibitors in recurrent platinum-sensitive EOC, providing recommendations for their management. Expert opinion: The clinical research over the next years will be focused on a more precise characterization of molecular pathways underlying tumorigenesis of the five ovarian tumors, to improve the decision-making process in these rare diseases. For this purpose, new study designs and international collaborations will become mandatory. Immunotherapy, antiangiogenic agents and PARP inhibitors will be combined to build a treatment strategy algorithm which will allow patients to receive all the available treatment option, in the more appropriate sequence.

Optimal Classes of Chemotherapeutic Agents Sensitized by Specific Small-Molecule Inhibitors of Akt In Vitro and In Vivo

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Yan Shi

2005-11-01

Full Text Available Akt is a serine/threonine kinase that transduces survival signals from survival/growth factors. Deregulation and signal imbalance in cancer cells make them prone to apoptosis. Upregulation or activation of Akt to aid the survival of cancer cells is a common theme in human malignancies. We have developed small-molecule Akt inhibitors that are potent and specific. These Akt inhibitors can inhibit Akt activity and block phosphorylation by Akt on multiple downstream targets in cells. Synergy in apoptosis induction was observed when Akt inhibitors were combined with doxorubicin or camptothecin. Akt inhibitor-induced enhancement of topoisomerase inhibitor cytotoxicity was also evident in long-term cell survival assay. Synergy with paclitaxel in apoptosis induction was evident in cells pretreated with paclitaxel, and enhancement of tumor delay by paclitaxel was demonstrated through cotreatment with Akt inhibitor Compound A (A-443654. Combination with other classes of chemotherapeutic agents did not yield any enhancement of cytotoxicity. These findings provide important guidance in selecting appropriate classes of chemotherapeutic agents for combination with Akt inhibitors in cancer treatment.

Developments in platinum anticancer drugs

Science.gov (United States)

Tylkowski, Bartosz; Jastrząb, Renata; Odani, Akira

2018-01-01

Platinum compounds represent one of the great success stories of metals in medicine. Following the unexpected discovery of the anticancer activity of cisplatin (Fig. 1) in 1965 by Prof. Rosenberg [1], a large number of its variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. Although cisplatin has been in use for over four decades, new and more effective platinum-based therapeutics are finally on the horizon. A wide introduction to anticancer studies is given by the authors of the previous chapter. This chapter aims at providing the readers with a comprehensive and in-depth understanding of recent developments of platinum anticancer drugs and to review the state of the art. The chapter is divided into two parts. In the first part we present a historical aspect of platinum and its complexes, while in the second part we give an overview of developments in the field of platinum anticancer agents.

A Potential Bone-Targeting Hypotoxic Platinum(II) Complex with an Unusual Cytostatic Mechanism toward Osteosarcoma Cells.

Science.gov (United States)

Zhang, Zhenqin; Zhu, Zhenzhu; Luo, Cheng; Zhu, Chengcheng; Zhang, Changli; Guo, Zijian; Wang, Xiaoyong

2018-03-19

Osteosarcoma (OS) is the most common primary pediatric bone tumor lethal to children and adolescents. Chemotherapeutic agents such as cisplatin are not effective for OS because of their poor accessibility to this cancer and severe systemic toxicity. In this study, a lipophilic platinum(II) complex bearing a bisphosphonate bone-targeting moiety, cis-[PtL(NH 3 ) 2 Cl]NO 3 {BPP; L = tetraethyl [2-(pyridin-2-yl)ethane-1,1-diyl]bisphosphonate}, was prepared and characterized by NMR, electrospray ionization mass spectrometry, and single-crystal X-ray crystallography. The cytotoxicity of BPP toward OS cell lines U2OS and MG-63 was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. BPP exhibits moderate inhibition against U2OS cells through a mechanism involving both DNA binding and a mevalonate pathway. The acute toxicity of BPP to mice is 7-fold lower than that of cisplatin. The relative low systemic toxicity may result from the steric hindrance of the ligand, which blocks BPP approaching the bases of DNA. The results suggest that incorporating bisphosphonates into a platinum complex not only enhances its bone-targeting property but also minimizes its reactivity toward DNA and thereby lowers the systematic toxicity of the complex. The diminished cytotoxicity of BPP could be compensated for by increasing the therapeutic dose with marginal harm. This strategy provides a new possibility for overcoming the ineffectiveness and systemic toxicity of platinum drugs in the treatment of OS.

Stability Studies of Certain Chemotherapeutic Agents Following Gamma Irradiation and Silver Nanoparticles Conjugation

International Nuclear Information System (INIS)

El-Sayyad, Gh.E.S.M.

2014-01-01

The Chemical stability of drug is of great importance since it becomes less effective as it undergoes degradation in case of applied of gamma irradiation process. The application of gamma irradiation for different chemotherapeutic agents Such as (ofloxacin, sodium ampicillin, sodium cefotaxime, gentamycin and amoxicillin) and studying the effect of applied doses on chemical structure and biological activity of the irradiated antibiotics compared to unirradiated ones was studied by ultraviolet-Visible spectrophotometer (UV-Visible), Fourier transform infrared spectroscopy measurements (FTIR spectra) and high performance liquid chromatography (HPLC) in addition to microbiological assay were run before and after irradiation to probe any change after irradiation. The results showed that all of the irradiated compounds remain stable and radio resistant; retaining their structure and activity unchanged up to 25 KGy. The radiation-induced AgNPs synthesis is a simple, clean which involves radiolysis of aqueous solution that provides an efficient method to reduce metal ions. Also, in this study, Bacillus megaterium was found to be an effective biological tool for the extracellular biosynthesis of stable AgNPs which are highly stable and this method has advantages over other methods as the organism used here is safe. This study would therefore lead to an easy procedure for producing silver nanoparticles with the added advantage of bio safety. The Synthesized AgNPs exhibit remarkable antimicrobial activity against both Gram-positive and Gram negative bacterial strains regardless of their drug-resistant mechanisms. The bactericidal activity have proved that AgNPs kill bacteria at such low concentrations (units of ppm), which Stability Studies of Certain Chemotherapeutic Agents Following Gamma Irradiation and Silver Nanoparticles Conjugation. do not reveal acute toxic effects on human cell, in addition to overcoming resistance, and lowering cost when compared to conventional

Pan-cancer analysis of genomic scar signatures associated with homologous recombination deficiency suggests novel indications for existing cancer drugs

DEFF Research Database (Denmark)

Marquard, Andrea Marion; Eklund, Aron Charles; Joshi, Tejal

2015-01-01

Ovarian and triple-negative breast cancers with BRCA1 or BRCA2 loss are highly sensitive to treatment with PARP inhibitors and platinum-based cytotoxic agents and show an accumulation of genomic scars in the form of gross DNA copy number aberrations. Cancers without BRCA1 or BRCA2 loss...... but with accumulation of similar genomic scars also show increased sensitivity to platinum-based chemotherapy. Therefore, reliable biomarkers to identify DNA repair-deficient cancers prior to treatment may be useful for directing patients to platinum chemotherapy and possibly PARP inhibitors. Recently, three SNP array...... may be strong candidates for clinical trials with PARP inhibitors or platinum-based chemotherapeutic regimens....

Base excision repair of chemotherapeutically-induced alkylated DNA damage predominantly causes contractions of expanded GAA repeats associated with Friedreich's ataxia.

Directory of Open Access Journals (Sweden)

Yanhao Lai

Full Text Available Expansion of GAA·TTC repeats within the first intron of the frataxin gene is the cause of Friedreich's ataxia (FRDA, an autosomal recessive neurodegenerative disorder. However, no effective treatment for the disease has been developed as yet. In this study, we explored a possibility of shortening expanded GAA repeats associated with FRDA through chemotherapeutically-induced DNA base lesions and subsequent base excision repair (BER. We provide the first evidence that alkylated DNA damage induced by temozolomide, a chemotherapeutic DNA damaging agent can induce massive GAA repeat contractions/deletions, but only limited expansions in FRDA patient lymphoblasts. We showed that temozolomide-induced GAA repeat instability was mediated by BER. Further characterization of BER of an abasic site in the context of (GAA20 repeats indicates that the lesion mainly resulted in a large deletion of 8 repeats along with small expansions. This was because temozolomide-induced single-stranded breaks initially led to DNA slippage and the formation of a small GAA repeat loop in the upstream region of the damaged strand and a small TTC loop on the template strand. This allowed limited pol β DNA synthesis and the formation of a short 5'-GAA repeat flap that was cleaved by FEN1, thereby leading to small repeat expansions. At a later stage of BER, the small template loop expanded into a large template loop that resulted in the formation of a long 5'-GAA repeat flap. Pol β then performed limited DNA synthesis to bypass the loop, and FEN1 removed the long repeat flap ultimately causing a large repeat deletion. Our study indicates that chemotherapeutically-induced alkylated DNA damage can induce large contractions/deletions of expanded GAA repeats through BER in FRDA patient cells. This further suggests the potential of developing chemotherapeutic alkylating agents to shorten expanded GAA repeats for treatment of FRDA.

Synergy of irofulven in combination with other DNA damaging agents: synergistic interaction with altretamine, alkylating, and platinum-derived agents in the MV522 lung tumor model.

Science.gov (United States)

Kelner, Michael J; McMorris, Trevor C; Rojas, Rafael J; Estes, Leita A; Suthipinijtham, Pharnuk

2008-12-01

Irofulven (MGI 114, NSC 683863) is a semisynthetic derivative of illudin S, a natural product present in the Omphalotus illudins (Jack O'Lantern) mushroom. This novel agent produces DNA damage, that in contrast to other agents, is predominately ignored by the global genome repair pathway of the nucleotide excision repair (NER)(2) system. The aim of this study was to determine the antitumor activity of irofulven when administered in combination with 44 different DNA damaging agents, whose damage is in general detected and repaired by the genome repair pathway. The human lung carcinoma MV522 cell line and its corresponding xenograft model were used to evaluate the activity of irofulven in combination with different DNA damaging agents. Two main classes of DNA damaging agents, platinum-derived agents, and select bifunctional alkylating agents, demonstrated in vivo synergistic or super-additive interaction with irofulven. DNA helicase inhibiting agents also demonstrated synergy in vitro, but an enhanced interaction with irofulven could not be demonstrated in vivo. There was no detectable synergistic activity between irofulven and agents capable of inducing DNA cleavage or intercalating into DNA. These results indicate that the antitumor activity of irofulven is enhanced when combined with platinum-derived agents, altretamine, and select alkylating agents such as melphalan or chlorambucil. A common factor between these agents appears to be the production of intrastrand DNA crosslinks. The synergistic interaction between irofulven and other agents may stem from the nucleotide excision repair system being selectively overwhelmed at two distinct points in the pathway, resulting in prolonged stalling of transcription forks, and subsequent initiation of apoptosis.

PET studies of potential chemotherapeutic agents: Pt. 10; Synthesis of ''no-carrier-added'' ( sup 11 C)-HECNU: the hydroxyethyl analog of the chemotherapeutic agent BCNU

Energy Technology Data Exchange (ETDEWEB)

Conway, T.; Diksic, M. (Montreal Neurological Inst. and Hospital, PQ (Canada). McConnell Brain Imaging Centre McGill Univ., Montreal, PQ (Canada). Dept. of Neurology and Neurosurgery)

1991-01-01

Carbon-11-labeled HECNU (1-(2-chloroethyl)-1-nitroso-3-(2-hydroxyethyl) urea) a potential chemotherapeutic agent, has been prepared by the nitrosation of the corresponding carbon-11-labeled urea, HECU, (1-(2-chloroethyl)-3-(2-hydroxyethyl) urea). The isomeric byproduct of nitrosation, 1-(2-chloroethyl)-3-nitroso-3-(2-hydroxyethyl) urea can be efficiently removed by preparative scale HPLC on a Partisil column. ({sup 11}C)-HECU was prepared by reacting ethanolamine with ({sup 11}C)-2-chloroethyl-isocyanate which was itself prepared by reacting ({sup 11}C)-phosgene with 2-chloroethylamine hydrochloride suspended in dioxane at 60-65{sup o}C. This synthesis yielded ({sup 11}C)-HECNU with an average radiochemical purity of 98% in an average radiochemical yield of 18% relative to the radioactivity measured at the end of the {sup 11}C-phosgene introduction. (author).

Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents in non-small cell lung cancer cells

Directory of Open Access Journals (Sweden)

Coffey Matthew C

2009-07-01

Full Text Available Abstract Background Reovirus type 3 Dearing strain (ReoT3D has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safety and potential efficacy are currently being investigated in early clinical trials. In this study, we investigated the in vitro combination effects of ReoT3D and chemotherapeutic agents against human non-small cell lung cancer (NSCLC. Results ReoT3D alone exerted significant cytolytic activity in 7 of 9 NSCLC cell lines examined, with the 50% effective dose, defined as the initial virus dose to achieve 50% cell killing after 48 hours of infection, ranging from 1.46 ± 0.12 ~2.68 ± 0.25 (mean ± SD log10 pfu/cell. Chou-Talalay analysis of the combination of ReoT3D with cisplatin, gemcitabine, or vinblastine demonstrated strong synergistic effects on cell killing, but only in cell lines that were sensitive to these compounds. In contrast, the combination of ReoT3D and paclitaxel was invariably synergistic in all cell lines tested, regardless of their levels of sensitivity to either agent. Treatment of NSCLC cell lines with the ReoT3D-paclitaxel combination resulted in increased poly (ADP-ribose polymerase cleavage and caspase activity compared to single therapy, indicating enhanced apoptosis induction in dually treated NSCLC cells. NSCLC cells treated with the ReoT3D-paclitaxel combination showed increased proportions of mitotic and apoptotic cells, and a more pronounced level of caspase-3 activation was demonstrated in mitotically arrested cells. Conclusion These data suggest that the oncolytic activity of ReoT3D can be potentiated by taxanes and other chemotherapeutic agents, and that the ReoT3D-taxane combination most effectively achieves synergy through accelerated apoptosis triggered by prolonged mitotic arrest.

Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

International Nuclear Information System (INIS)

Peng, Hui; Wang, Huihui; Xue, Peng; Hou, Yongyong; Dong, Jian; Zhou, Tong; Qu, Weidong; Peng, Shuangqing; Li, Jin; Carmichael, Paul L.; Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

2016-01-01

Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As 2 O 3 ), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As 2 O 3 -challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As 2 O 3 -induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As 2 O 3 -induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As 2 O 3 in AML cells. • Sensitization of THP-1 cells to As 2 O 3 toxicity by ethionamide is NRF2-dependent.

Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

Science.gov (United States)

Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

2017-05-01

AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

1,3-Bis(2-chloroethyl-1-nitrosourea-loaded bovine serum albumin nanoparticles with dual magnetic resonance–fluorescence imaging for tracking of chemotherapeutic agents

Directory of Open Access Journals (Sweden)

Wei KC

2016-08-01

Full Text Available Kuo-Chen Wei,1 Feng-Wei Lin,2 Chiung-Yin Huang,1 Chen-Chi M Ma,3 Ju-Yu Chen,1 Li-Ying Feng,1 Hung-Wei Yang2 1Department of Neurosurgery, Chang Gung Memorial Hospital, School of Medicine, Chang Gung University, Taoyuan, 2Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, 3Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China Abstract: To date, knowing how to identify the location of chemotherapeutic agents in the human body after injection is still a challenge. Therefore, it is urgent to develop a drug delivery system with molecular imaging tracking ability to accurately understand the distribution, location, and concentration of a drug in living organisms. In this study, we developed bovine serum albumin (BSA-based nanoparticles (NPs with dual magnetic resonance (MR and fluorescence imaging modalities (fluorescein isothiocyanate [FITC]-BSA-Gd/1,3-bis(2-chloroethyl-1-nitrosourea [BCNU] NPs to deliver BCNU for inhibition of brain tumor cells (MBR 261-2. These BSA-based NPs are water dispersible, stable, and biocompatible as confirmed by XTT cell viability assay. In vitro phantoms and in vivo MR and fluorescence imaging experiments show that the developed FITC-BSA-Gd/BCNU NPs enable dual MR and fluorescence imaging for monitoring cellular uptake and distribution in tumors. The T1 relaxivity (R1 of FITC-BSA-Gd/BCNU NPs was 3.25 mM-1 s-1, which was similar to that of the commercial T1 contrast agent (R1 =3.36 mM-1 s-1. The results indicate that this multifunctional drug delivery system has potential bioimaging tracking of chemotherapeutic agents ability in vitro and in vivo for cancer therapy. Keywords: drug tracking, fluorescence imaging, MR imaging, BSA nanoparticles, cancer therapy

Participation of MT3 melatonin receptors in the synergistic effect of melatonin on cytotoxic and apoptotic actions evoked by chemotherapeutics.

Science.gov (United States)

Pariente, Roberto; Bejarano, Ignacio; Espino, Javier; Rodríguez, Ana B; Pariente, José A

2017-11-01

Melatonin has antitumor activity via several mechanisms including its antiproliferative and proapoptotic effects in addition to its potent antioxidant actions. Therefore, melatonin may be useful in the treatment of tumors in association with chemotherapy drugs. This study was performed to study the role of melatonin receptors on the cytotoxicity and apoptosis induced by the chemotherapeutic agents cisplatin and 5-fluorouracil in two tumor cell lines, such as human colorectal cancer HT-29 cells and cervical cancer HeLa cells. We found that both melatonin and the two chemotherapeutic agents tested induced a decrease in HT-29 and HeLa cell viability. Furthermore, melatonin significantly increased the cytotoxic effect of chemotherapeutic agents, particularly, in 5-fluorouracil-challenged cells. Stimulation of cells with either of the two chemotherapeutic agents in the presence of melatonin further increased caspase-3 activation. Concomitant treatments with melatonin and chemotherapeutic agents augmented the population of apoptotic cells compared to the treatments with chemotherapeutics alone. Blockade of MT1 and/or MT2 receptors with luzindole or 4-P-PDOT was unable to reverse the enhancing effects of melatonin on both cytotoxicity, caspase-3 activation and the amount of apoptotic cells evoked by the chemotherapeutic agents, whereas when MT3 receptors were blocked with prazosin, the synergistic effect of melatonin with chemotherapy on cytotoxicity and apoptosis was reversed. Our findings provided evidence that in vitro melatonin strongly enhances chemotherapeutic-induced cytotoxicity and apoptosis in two tumor cell lines, namely HT-29 and HeLa cells and, this potentiating effect of melatonin is mediated by MT3 receptor stimulation.

[Relationship between sensitivity of tumor cells to chemotherapeutic agent in vivo and in vitro: experiment with mouse lymphoma cells].

Science.gov (United States)

Li, Chuan-gang; Li, Mo-lin; Shu, Xiao-hong; Jia, Yu-jie; Liu, Yong-ji; Li, Ming

2007-06-12

To study the relationship of the sensitivity of tumor cells to chemotherapeutic agent between in vivo and in vitro. Mouse lymphoma cells of the line E14 were cultured and melphalan resistant EL4 cell line (EL4/melphalan) was established by culturing EL4 cells with continuous low-concentration and intermittent gradually-increasing-concentration of melphalan in vitro. MTT assay was used to evaluate the drug sensitivity and the resistance index of the EL4/melphalan cells to melphalan was calculated. EL4/melphalan and EL4 cells of the concentration of 5 x 10(8)/L were inoculated separately into 20 C57BL/6 mice subcutaneously. 12 days later, the EL4 and EL4/melphalan tumor-bearing mice were randomly divided into 2 groups respectively, 5 mice in each group. Treatment groups were given 7.5 mg/kg melphalan intraperitoneally, and control groups were given the same volume of normal saline. The tumor size was observed every other day. Compared with the EL4 cells, the EL4/melphalan cells had no obvious changes morphologically. They could grow in RPMI 1640 medium containing 5 mg/ml melphalan. The resistance index was 2.87 against melphalan. After the treatment of melphalan of the dose 7.5 mg/kg, the tumor sizes of the treatment groups and control groups inoculated with both EL4 cells and the EL4/melphalan cells gradually decreased at the similar speed, and about one week later all tumors disappeared. However, the tumors of the control groups grew progressively and all the mice died at last. The chemotherapeutic effects of tumors in vivo have nothing to do with the effects of the chemotherapeutic agents on tumor cells in vitro. The tumor cells resistant to melphalan in vitro remain sensitive to the drug in vivo.

Basophil Activation Test is a Relevant Biomarker of the Outcome of Rapid Desensitization in Platinum Compounds-Allergy.

Science.gov (United States)

Giavina-Bianchi, Pedro; Galvão, Violeta Régnier; Picard, Matthieu; Caiado, Joana; Castells, Mariana C

Rapid drug desensitization (RDD) has become a cornerstone in the management of immediate drug hypersensitivity reactions (DHRs) to chemotherapeutic agents. Because of the inherent risk of anaphylaxis during RDD, biomarkers to predict patients at risk of developing such severe reactions are needed. The basophil activation test (BAT) has been used in DHRs as a diagnostic tool. We evaluated basophil CD63 and CD203c expression (BAT) as a biomarker to assess the safety and effectiveness of RDD in platinum compounds-allergic patients. Patients allergic to platinum compounds (n = 15) undergoing RDD were assessed through clinical history, skin testing, serum tryptase levels, and BAT. BAT was performed immediately before RDD, assessing CD203c and CD63 expression on basophils. BAT was also performed in 6 patients tolerant to platinum compounds and in 6 healthy volunteers. BAT was positive to CD203c or CD63 in 11 out of 15 patients allergic to platinum compounds (73%), with increased expression of CD203c and CD63 in 11 (73%) and 6 (40%) patients, respectively. Increased CD63 expression tended to be associated with more severe initial reactions. All controls had negative test results. Reactions during RDD were associated with BAT positivity and increased tryptase levels. Only 1 of 4 patients with negative BAT had a mild reaction during RDD. BAT remained positive in multiple sequential RDD. BAT identified patients allergic to platinum compounds with an increased risk of reactions during desensitization and higher CD63 expression was observed in severe reactions. Multiple RDDs to platinum compounds did not induce persistent hyporesponsiveness on basophils. BAT is a potential biomarker for RDD. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Platinum metals in the environment

Energy Technology Data Exchange (ETDEWEB)

Zereini, Fathi [Frankfurt Univ. (Germany). Dept. of Environmental Analytical Chemistry; Wiseman, Clare L.S. (ed.) [Toronto Univ. (Canada). School of the Environment

2015-03-01

This book contains the five chapters with the following topics: 1. SOURCES OF PGE EMISSIONS ELEMENTS: Sources of Platinum Group Elements (PGE) in the Environment; Impact of Platinum Group Element Emissions from Mining and Production Activities. 2. ANALYTICAL METHODS FOR THE DETERMINATION OF PGE IN BIOLOGICAL AND ENVIRONMENTAL MATRICES: Appraisal of Biosorption for Recovery, Separation and Determination of Platinum, Palladium and Rhodium in Environmental Samples; On the Underestimated Factors Influencing the Accuracy of Determination of Pt and Pd by Electrothermal Atomic Absorption Spectrometry in Road Dust Samples; Application of Solid Sorbents for Enrichment and Separation of Platinum Metal Ions; Voltammetric Analysis of Platinum in Environmental Matrices; Speciation Analysis of Chloroplatinates; Analysis of Platinum Group Elements in Environmental Samples: A Review. 3. OCCURRENCE, CHEMICAL BEHAVIOR AND FATE OF PGE IN THE ENVIRONMENT: Brazilian PGE Research Data Survey on Urban and Roadside Soils; Platinum, Palladium and Rhodium in a Bavarian Roadside Soil; Increase of Platinum Group Element Concentrations in Soils and Airborne Dust During the Period of Vehicular Exhaust Catalysts Introduction; Platinum-Group Elements in Urban Fluvial Bed Sediments-Hawaii; Long-Term Monitoring of Palladium and Platinum Contents in Road Dust of the City of Munich, Germany; Characterization of PGEs and Other Elements in Road Dusts and Airborne Particles in Houston, Texas; Accumulation and Distribution of Pt and Pd in Roadside Dust, Soil and Vegetation in Bulgaria; Increase of the Environmental Pt Concentration in the Metropolitan Area of Mexico City Associated to the Use of Automobile Catalytic Converters; Solubility of Emitted Platinum Group Elements (Pt, Pd and Rh) in Airborne Particulate Matter (PM10) in the Presence of Organic Complexing Agents; The Influence of Anionic Species (Cl{sup -}, NO{sub 3}{sup -}, SO{sub 4}{sup 2-}) on the Transformation and Solubility of Platinum in

Effects of repeated administration of chemotherapeutic agents tamoxifen, methotrexate, and 5-fluorouracil on the acquisition and retention of a learned response in mice

Science.gov (United States)

Foley, John J.; Clark-Vetri, Rachel; Raffa, Robert B.

2011-01-01

Rationale A number of cancer chemotherapeutic agents have been associated with a loss of memory in breast cancer patients although little is known of the causality of this effect. Objectives To assess the potential cognitive effects of repeated exposure to chemotherapeutic agents, we administered the selective estrogen receptor modulator tamoxifen or the antimetabolite chemotherapy, methotrexate, and 5-fluorouracil, alone and in combination to mice and tested them in a learning and memory assay. Methods Swiss-Webster male mice were injected with saline, 32 mg/kg tamoxifen, 3.2 or 32 mg/kg methotrexate, 75 mg/kg 5-fluorouracil, 3.2 or 32 mg/kg methotrexate in combination with 75 mg/kg 5-fluorouracil once per week for 3 weeks. On days 23 and 24, mice were tested for acquisition and retention of a nose-poke response in a learning procedure called autoshaping. In addition, the acute effects of tamoxifen were assessed in additional mice in a similar procedure. Results The chemotherapeutic agents alone and in combination reduced body weight relative to saline treatment over the course of 4 weeks. Repeated treatment with tamoxifen produced both acquisition and retention effects relative to the saline-treated group although acute tamoxifen was without effect except at a behaviorally toxic dose. Repeated treatment with methotrexate in combination with 5-fluorouracil produced effects on retention, but the magnitude of these changes depended on the methotrexate dose. Conclusions These data demonstrate that repeated administration of tamoxifen or certain combination of methotrexate and 5-fluorouracil may produce deficits in the acquisition or retention of learned responses which suggest potential strategies for prevention or remediation might be considered in vulnerable patient populations. PMID:21537942

Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

Energy Technology Data Exchange (ETDEWEB)

Peng, Hui [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Wang, Huihui [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Xue, Peng [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Hou, Yongyong [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Dong, Jian [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan (China); Zhou, Tong [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Peng, Shuangqing [Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Li, Jin; Carmichael, Paul L. [Unilever, Safety & Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Pi, Jingbo, E-mail: jpi@mail.cmu.edu.cn [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States)

2016-02-01

Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As{sub 2}O{sub 3}), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As{sub 2}O{sub 3}-challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As{sub 2}O{sub 3}-induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As{sub 2}O{sub 3}-induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As{sub 2}O{sub 3} in AML cells. • Sensitization of THP-1 cells to As{sub 2}O{sub 3} toxicity by ethionamide is NRF2-dependent.

Photodynamic killing of cancer cells by a Platinum(II) complex with cyclometallating ligand

Science.gov (United States)

Doherty, Rachel E.; Sazanovich, Igor V.; McKenzie, Luke K.; Stasheuski, Alexander S.; Coyle, Rachel; Baggaley, Elizabeth; Bottomley, Sarah; Weinstein, Julia A.; Bryant, Helen E.

2016-03-01

Photodynamic therapy that uses photosensitizers which only become toxic upon light-irradiation provides a strong alternative to conventional cancer treatment due to its ability to selectively target tumour material without affecting healthy tissue. Transition metal complexes are highly promising PDT agents due to intense visible light absorption, yet the majority are toxic even without light. This study introduces a small, photostable, charge-neutral platinum-based compound, Pt(II) 2,6-dipyrido-4-methyl-benzenechloride, complex 1, as a photosensitizer, which works under visible light. Activation of the new photosensitizer at low concentrations (0.1-1 μM) by comparatively low dose of 405 nm light (3.6 J cm-2) causes significant cell death of cervical, colorectal and bladder cancer cell lines, and, importantly, a cisplatin resistant cell line EJ-R. The photo-index of the complex is 8. We demonstrate that complex 1 induces irreversible DNA single strand breaks following irradiation, and that oxygen is essential for the photoinduced action. Neither light, nor compound alone led to cell death. The key advantages of the new drug include a remarkably fast accumulation time (diffusion-controlled, minutes), and photostability. This study demonstrates a highly promising new agent for photodynamic therapy, and attracts attention to photostable metal complexes as viable alternatives to conventional chemotherapeutics, such as cisplatin.

An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

NARCIS (Netherlands)

Vollebergh, M. A.; Lips, E. H.; Nederlof, P. M.; Wessels, L. F. A.; Schmidt, M. K.; van Beers, E. H.; Cornelissen, S.; Holtkamp, M.; Froklage, F. E.; de Vries, E. G. E.; Schrama, J. G.; Wesseling, J.; van de Vijver, M. J.; van Tinteren, H.; de Bruin, Michiel; Hauptmann, M.; Rodenhuis, S.; Linn, S. C.

2011-01-01

Breast cancer cells deficient for BRCA1 are hypersensitive to agents inducing DNA double-strand breaks (DSB), such as bifunctional alkylators and platinum agents. Earlier, we had developed a comparative genomic hybridisation (CGH) classifier based on BRCA1-mutated breast cancers. We hypothesised

Effect of time intervals between irradiation and chemotherapeutic agents on the normal tissue damage. Comparison between in vivo and in vitro experiments

Energy Technology Data Exchange (ETDEWEB)

Ito, Hisao; Nakayama, Toshitake; Hashimoto, Shozo (Keio Univ., Tokyo (Japan). School of Medicine)

1989-05-01

Experiments have been carried out to determine the effect on the cell survivals at different time intervals between irradiation and chemotherapeutic agents (BLM, cisDDP, ADM and ACNU) in either the in vivo or the in vitro system. The intestinal epithelial assay was applied on the in vivo system. The clonogenic cell survivals of V/sub 79/ cells, both in the proliferative and the plateau phases, were determined in the in vitro system. The V/sub 79/ cells in the plateau phase were more sensitive to BLM, cisDDP and ACNU than those in the proliferative phase, however, the result was reverse with ADM. When BLM, cisDDP or ACNU was combined with irradiation at different time intervals, the response of the plateau phase V/sub 79/ cells to combination therapies were very similar to those of the intestinal epithelial cells. On the other hand, V/sub 79/ cells in the proliferative phase, which were treated with ADM and irradiation, showed the similar response as the intestinal cells. These results suggest that studies of chemo-radiotherapy with cultured cells which are sensitive to chemotherapeutic agents might be suitable to expect the in vivo damage of the normal tissue. (author).

Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

KAUST Repository

Kieler-Ferguson, Heidi M.; Frechet, Jean; Szoka, Francis C.

2013-01-01

For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting

The use of chemotherapeutics for the treatment of keloid scars

Directory of Open Access Journals (Sweden)

Christopher David Jones

2015-05-01

Full Text Available Keloid scars are pathological scars, which develop as a result of exaggerated dermal tissue proliferation following cutaneous injury and often cause physical, psychological and cosmetic problems. Various theories regarding keloidogenesis exist, however the precise pathophysiological events remain unclear. Many different treatment modalities have been implicated in their management, but currently there is no entirely satisfactory method for treating all keloid lesions. We review a number of different chemotherapeutic agents which have been proposed for the treatment of keloid and hypertrophic scars while giving insight into some of the novel chemotherapeutic drugs which are currently being investigated. Non-randomized trials evaluating the influence of different chemotherapeutic agents, such as 5-fluorouracil (5-FU; mitomycin C; bleomycin and steroid injection, either alone or in combination with other chemotherapeutic agents or alternative treatment modalities, for the treatment of keloids were identified using a predefined PubMed search strategy. Twenty seven papers were identified. Scar improvement ≥50% was found in the majority of cases treated with 5-FU, with similar results found for mitomycin C, bleomycin and steroid injection. Combined intralesional 5-FU and steroid injection produced statistically significant improvements when compared to monotherapy. Monotherapy recurrence rates ranged from 0-47% for 5-FU, 0-15% for bleomycin and 0-50% for steroid injection. However, combined therapy in the form of surgical excision and adjuvant 5-FU or steroid injections demonstrated lower recurrence rates; 19% and 6% respectively. Currently, most of the literature supports the use of combination therapy (usually surgery and adjuvant chemotherapy as the mainstay treatment of keloids, however further investigation is necessary to determine success rates over longer time frames. Furthermore, there is the potential for novel therapies, but further

Suspension culture combined with chemotherapeutic agents for sorting of breast cancer stem cells

International Nuclear Information System (INIS)

Li, Hai-zhi; Yi, Tong-bo; Wu, Zheng-yan

2008-01-01

Cancer stem cell (CSC) hypothesis has not been well demonstrated by the lack of the most convincing evidence concerning a single cell capable of giving rise to a tumor. The scarcity in quantity and improper approaches for isolation and purification of CSCs have become the major obstacles for great development in CSCs. Here we adopted suspension culture combined with anticancer regimens as a strategy for screening breast cancer stem cells (BrCSCs). BrCSCs could survive and be highly enriched in non-adherent suspension culture while chemotherapeutic agents could destroy most rapidly dividing cancer cells and spare relatively quiescent BrCSCs. TM40D murine breast cancer cells were cultured in serum-free medium. The expression of CD44 + CD24 - was measured by flow cytometry. Cells of passage 10 were treated in combination with anticancer agents pacilitaxel and epirubicin at different peak plasma concentrations for 24 hours, and then maintained under suspension culture. The rate of apoptosis was examined by flow cytometry with Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining method. Selected cells in different amounts were injected subcutaneously into BALB/C mice to observe tumor formation. Cells of passage 10 in suspension culture had the highest percentage of CD44 + CD24 - (about 77 percent). A single tumor cell in 0.35 PPC could generate tumors in 3 of 20 BALB/C mice. Suspension culture combined with anticancer regimens provides an effective means of isolating, culturing and purifying BrCSCs

Polymeric micelles with ionic cores containing biodegradable cross-links for delivery of chemotherapeutic agents.

Science.gov (United States)

Kim, Jong Oh; Sahay, Gaurav; Kabanov, Alexander V; Bronich, Tatiana K

2010-04-12

Novel functional polymeric nanocarriers with ionic cores containing biodegradable cross-links were developed for delivery of chemotherapeutic agents. Block ionomer complexes (BIC) of poly(ethylene oxide)-b-poly(methacylic acid) (PEO-b-PMA) and divalent metal cations (Ca(2+)) were utilized as templates. Disulfide bonds were introduced into the ionic cores by using cystamine as a biodegradable cross-linker. The resulting cross-linked micelles with disulfide bonds represented soft, hydrogel-like nanospheres and demonstrated a time-dependent degradation in the conditions mimicking the intracellular reducing environment. The ionic character of the cores allowed to achieve a very high level of doxorubicin (DOX) loading (50% w/w) into the cross-linked micelles. DOX-loaded degradable cross-linked micelles exhibited more potent cytotoxicity against human A2780 ovarian carcinoma cells as compared to micellar formulations without disulfide linkages. These novel biodegradable cross-linked micelles are expected to be attractive candidates for delivery of anticancer drugs.

Enterobacter and Klebsiella species isolated from fresh vegetables marketed in Valencia (Spain) and their clinically relevant resistances to chemotherapeutic agents.

Science.gov (United States)

Falomir, María Pilar; Rico, Hortensia; Gozalbo, Daniel

2013-12-01

Occurrence of antibiotic-resistant pathogenic or commensal enterobacteria in marketed agricultural foodstuffs may contribute to their incorporation into the food chain and constitutes an additional food safety concern. In this work, we have determined the clinically relevant resistances to 11 common chemotherapeutic agents in Enterobacter and Klebsiella isolates from fresh vegetables from various sources (supermarkets and greengrocers' shops in Valencia, Spain). A total of 96 isolates were obtained from 160 vegetables analyzed (50% positive samples): 68 Enterobacter isolates (59 E. cloacae, two E. aerogenes, two E. cancerogenus, one E. gergoviae, and four E. sakazakii, currently Cronobacter spp.), and 28 Klebsiella isolates (19 K. oxytoca and 9 K. pneumoniae). Only seven isolates were susceptible to all agents tested, and no resistances to ceftazidime, ciprofloxacin, gentamicin, and chloramphenicol were detected. Most isolates were resistant to amoxicillin/clavulanic acid (74 [58 Enterobacter and 16 Klebsiella]) or to ampicillin (80 [55/25]). Other resistances were less frequent: nitrofurantoin (13 isolates [12/1]), tetracycline (6 [5/1]), co-trimoxazole (3 [3/0]), cefotaxime (1 [1/0]), and streptomycin (2 [1/1]). Multiresistant isolates to two (56 [41/15]), three (10 E. cloacae isolates), four (one E. cloacae and one K. pneumoniae isolate), and five (two E. cloacae isolates) chemotherapeutic agents were also detected. The presence of potential pathogens points to marketed fresh produce, which often is eaten raw, as a risk factor for consumer health. In addition, these results support the usefulness of these bacterial species as indicators of the spreading of antibiotic resistances into the environment, particularly in the food chain, and suggest their role as carriers of resistance determinants from farms to consumers, which may constitute an additional "silent" food safety concern. Therefore, there is a need to improve the hygienic quality of marketed fresh

An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer.

Directory of Open Access Journals (Sweden)

Kelly H Salter

Full Text Available A major challenge in oncology is the selection of the most effective chemotherapeutic agents for individual patients, while the administration of ineffective chemotherapy increases mortality and decreases quality of life in cancer patients. This emphasizes the need to evaluate every patient's probability of responding to each chemotherapeutic agent and limiting the agents used to those most likely to be effective.Using gene expression data on the NCI-60 and corresponding drug sensitivity, mRNA and microRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel, 5-fluorouracil, adriamycin, and cyclophosphamide chemotherapy regimen. To further dissect the biology of resistance, we applied signatures of oncogenic pathway activation and performed hierarchical clustering. We then used mRNA signatures of chemotherapy sensitivity to identify alternative therapeutics for patients resistant to TFAC. Profiles from mRNA and microRNA expression data represent distinct biologic mechanisms of resistance to common cytotoxic agents. The individual mRNA signatures were validated in an independent dataset of breast tumors (P = 0.002, NPV = 82%. When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was found to be greater in basal-like than non basal-like patients (P = 0.03 and P = 0.06. Samples from patients with co-activated Myc and E2F represented the cohort with the lowest percentage (8% of responders. Using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04, representing a viable alternative therapy.Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding micro

Immunological detection and quantification of DNA components structurally modified by alkylating carcinogens, mutagens and chemotherapeutic agents

International Nuclear Information System (INIS)

Rajewsky, M.F.

1983-01-01

The detection and quantification of defined reaction products of chemical mutagens and carcinogens (and of many cancer chemotherapeutic agents) with DNA require highly sensitive analytical techniques. The exceptional capability of immunoglobulins to recognize subtle alterations of molecular structure (especially when monoclonal antibodies are used to maximize specificity), outstanding sensitivity of immunoanalysis by high-affinity antibodies, and the fact that radioactively-labelled agents are not required suggest the utility of a radioimmunoassay to recognize and quantitate alkylated DNA products. We have recently developed a set of high-affinity monoclonal antibodies (secreted by mouse x mouse as well as by rat x rat hybridomas; antibody affinity constants, 10 9 to > 10 10 lmol) specifically directed against several DNA alkylation products with possible relevance in relation to both mutagenesis and malignant transformation of mammalian cells. These alkylation products include 0 6 -N-butyldeoxyguanosine, and 0 4 -ethyldeoxythymidine. When used in a radioimmunassay, an antibody specific for 0 6 -ethyldeoxyguanosine, for example, will detect this product at an 0 6 -ethyldeoxyguanosine/deoxyguanosine molar ratio of approx. 3 x 10 -7 in a hydrolysate of 100 ug of DNA. The limit of detection can be lowered further if the respective alkyldeoxynucleosides are separated by HPLC from the DNA hydrolysate prior to the RIA. The anti-alkyldeoxynucleoside monoclonal antibodies can also be used to visualize, by immunostaining and fluorescence microscopy combined with electronic image intensification, specific alkylation products in the nuclear DNA of individual cells, and to localize structurally modified bases in double-stranded DNA molecules by transmission electron microscopy

Electrostatic Interaction of Negatively Charged Core–Shell Nanoparticles with Antitumoral Cationic Platinum-Based Complexes

Czech Academy of Sciences Publication Activity Database

Gál, Miroslav; Híveš, J.; Laus, M.; Sparnacci, K.; Ravera, M.; Gabano, E.; Osella, D.

-, č. 22 (2011), s. 3289-3294 ISSN 1434-1948 R&D Projects: GA ČR GP203/09/P502 Institutional research plan: CEZ:AV0Z40400503 Keywords : platinum * Antitumor agents * nanoparticles Subject RIV: CG - Electrochemistry Impact factor: 3.049, year: 2011

Nanostructured nanoparticles of self-assembled lipid pro-drugs as a route to improved chemotherapeutic agents

Energy Technology Data Exchange (ETDEWEB)

Sagnella, Sharon M.; Gong, Xiaojuan; Moghaddam, Minoo J.; Conn, Charlotte E.; Kimpton, Kathleen; Waddington, Lynne J.; Krodkiewska, Irena; Drummond, Calum J. (CSIRO/MSE); (CSIRO/LW)

2014-09-24

We demonstrate that oral delivery of self-assembled nanostructured nanoparticles consisting of 5-fluorouracil (5-FU) lipid prodrugs results in a highly effective, target-activated, chemotherapeutic agent, and offers significantly enhanced efficacy over a commercially available alternative that does not self-assemble. The lipid prodrug nanoparticles have been found to significantly slow the growth of a highly aggressive mouse 4T1 breast tumour, and essentially halt the growth of a human MDA-MB-231 breast tumour in mouse xenografts. Systemic toxicity is avoided as prodrug activation requires a three-step, enzymatic conversion to 5-FU, with the third step occurring preferentially at the tumour site. Additionally, differences in the lipid prodrug chemical structure and internal nanostructure of the nanoparticle dictate the enzymatic conversion rate and can be used to control sustained release profiles. Thus, we have developed novel oral nanomedicines that combine sustained release properties with target-selective activation.

Structure of matrix metalloproteinase-3 with a platinum-based inhibitor.

Science.gov (United States)

Belviso, Benny Danilo; Caliandro, Rocco; Siliqi, Dritan; Calderone, Vito; Arnesano, Fabio; Natile, Giovanni

2013-06-18

An X-ray investigation has been performed with the aim of characterizing the binding sites of a platinum-based inhibitor (K[PtCl3(DMSO)]) of matrix metalloproteinase-3 (stromelysin-1). The platinum complex targets His224 in the S1' specificity loop, representing the first step in the selective inhibition process (PDB ID code 4JA1).

Co-delivery of chemotherapeutics and proteins for synergistic therapy.

Science.gov (United States)

He, Chaoliang; Tang, Zhaohui; Tian, Huayu; Chen, Xuesi

2016-03-01

Combination therapy with chemotherapeutics and protein therapeutics, typically cytokines and antibodies, has been a type of crucial approaches for synergistic cancer treatment. However, conventional approaches by simultaneous administration of free chemotherapeutic drugs and proteins lead to limitations for further optimizing the synergistic effects, due to the distinct in vivo pharmacokinetics and distribution of small drugs and proteins, insufficient tumor selectivity and tumor accumulation, unpredictable drug/protein ratios at tumor sites, short half-lives, and serious systemic adverse effects. Consequently, to obtain optimal synergistic anti-tumor efficacy, considerable efforts have been devoted to develop the co-delivery systems for co-incorporating chemotherapeutics and proteins into a single carrier system and subsequently releasing the dual or multiple payloads at desired target sites in a more controllable manner. The co-delivery systems result in markedly enhanced blood stability and in vivo half-lives of the small drugs and proteins, elevated tumor accumulation, as well as the capability of delivering the multiple agents to the same target sites with rational drug/protein ratios, which may facilitate maximizing the synergistic effects and therefore lead to optimal antitumor efficacy. This review emphasizes the recent advances in the co-delivery systems for chemotherapeutics and proteins, typically cytokines and antibodies, for systemic or localized synergistic cancer treatment. Moreover, the proposed mechanisms responsible for the synergy of chemotherapeutic drugs and proteins are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

Science.gov (United States)

Yeo, Chien Ing; Ooi, Kah Kooi; Tiekink, Edward R T

2018-06-11

A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H₃N)₂PtCl₂], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.

Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics.

Science.gov (United States)

Garg, Abhishek D; More, Sanket; Rufo, Nicole; Mece, Odeta; Sassano, Maria Livia; Agostinis, Patrizia; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2017-01-01

The expression "immunogenic cell death" (ICD) refers to a functionally unique form of cell death that facilitates (instead of suppressing) a T cell-dependent immune response specific for dead cell-derived antigens. ICD critically relies on the activation of adaptive responses in dying cells, culminating with the exposure or secretion of immunostimulatory molecules commonly referred to as "damage-associated molecular patterns". Only a few agents can elicit bona fide ICD, including some clinically established chemotherapeutics such as doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin. In this Trial Watch, we discuss recent progress on the development of ICD-inducing chemotherapeutic regimens, focusing on studies that evaluate clinical efficacy in conjunction with immunological biomarkers.

GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

International Nuclear Information System (INIS)

Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

2011-01-01

Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

Outcomes with single agent LIPO-DOX in platinum-resistant ovarian and fallopian tube cancers and primary peritoneal adenocarcinoma - Chiang Mai University Hospital experience.

Science.gov (United States)

Suprasert, Prapaporn; Manopunya, Manatsawee; Cheewakriangkrai, Chalong

2014-01-01

Single pegylated liposomal doxorubicin (PLD) is commonly used as a salvage treatment in platinum-resistant ovarian cancer, fallopian tube cancer and primary peritoneal adenocarcinoma (PPA) with a satisfactory outcome. However, the data for second generation PLD administered in this setting are still limited. We conducted a retrospective study to evaluate the outcome of patients who received single-agent second generation PLD (LIPO-DOX) after the development of clinical platinum resistance. The study period was between March 2008 and March 2013. LIPO-DOX was administered intravenously 40 mg/m2 every 28 days until disease progression, but for not more than six cycles. The response rate was evaluated using the Gynecologic Cancer Intergroup (GCIG) criteria while the toxicity was evaluated according to WHO criteria. Twenty-nine patients met the inclusion criteria in the study period with an overall response rate of 13.8%. The median progression free survival and overall survival were three and eleven months, respectively. With the total of 96 cycles of chemotherapy, the patients developed grades 3 and 4 hematologic toxicity as follows: anemia, 0%, leukopenia, 9.6%, neutropenia, 32.3% and thrombocytopenia, 0%. In conclusion, the single agent second generation PLD demonstrated modest efficacy in patients with platinum-resistant ovarian cancer, fallopian tube cancer and PPA without serious toxicity.

APC selectively mediates response to chemotherapeutic agents in breast cancer

International Nuclear Information System (INIS)

VanKlompenberg, Monica K.; Bedalov, Claire O.; Soto, Katia Fernandez; Prosperi, Jenifer R.

2015-01-01

The Adenomatous Polyposis Coli (APC) tumor suppressor is mutated or hypermethylated in up to 70 % of sporadic breast cancers depending on subtype; however, the effects of APC mutation on tumorigenic properties remain unexplored. Using the Apc Min/+ mouse crossed to the Polyoma middle T antigen (PyMT) transgenic model, we identified enhanced breast tumorigenesis and alterations in genes critical in therapeutic resistance independent of Wnt/β-catenin signaling. Apc mutation changed the tumor histopathology from solid to squamous adenocarcinomas, resembling the highly aggressive human metaplastic breast cancer. Mechanistic studies in tumor-derived cell lines demonstrated that focal adhesion kinase (FAK)/Src/JNK signaling regulated the enhanced proliferation downstream of Apc mutation. Despite this mechanistic information, the role of APC in mediating breast cancer chemotherapeutic resistance is currently unknown. We have examined the effect of Apc loss in MMTV-PyMT mouse breast cancer cells on gene expression changes of ATP-binding cassette transporters and immunofluorescence to determine proliferative and apoptotic response of cells to cisplatin, doxorubicin and paclitaxel. Furthermore we determined the added effect of Src or JNK inhibition by PP2 and SP600125, respectively, on chemotherapeutic response. We also used the Aldefluor assay to measure the population of tumor initiating cells. Lastly, we measured the apoptotic and proliferative response to APC knockdown in MDA-MB-157 human breast cancer cells after chemotherapeutic treatment. Cells obtained from MMTV-PyMT;Apc Min/+ tumors express increased MDR1 (multidrug resistance protein 1), which is augmented by treatment with paclitaxel or doxorubicin. Furthermore MMTV-PyMT;Apc Min/+ cells are more resistant to cisplatin and doxorubicin-induced apoptosis, and show a larger population of ALDH positive cells. In the human metaplastic breast cancer cell line MDA-MB-157, APC knockdown led to paclitaxel and cisplatin

SEROTONIN METABOLISM FOLLOWING PLATINUM-BASED CHEMOTHERAPY COMBINED WITH THE SEROTONIN TYPE-3 ANTAGONIST TROPISETRON

NARCIS (Netherlands)

SCHRODER, CP; VANDERGRAAF, WTA; KEMA, IP; GROENEWEGEN, A; SLEIJFER, DT; DEVRIES, EGE

1995-01-01

The administration of platinum-based chemotherapy induces serotonin release from the enterochromaffin cells, causing nausea and vomiting. This study was conducted to evaluate parameters of serotonin metabolism following platinum-based chemotherapy given in combination with the serotonin type-3

TTFields alone and in combination with chemotherapeutic agents effectively reduce the viability of MDR cell sub-lines that over-express ABC transporters

International Nuclear Information System (INIS)

Schneiderman, Rosa S; Shmueli, Esther; Kirson, Eilon D; Palti, Yoram

2010-01-01

Exposure of cancer cells to chemotherapeutic agents may result in reduced sensitivity to structurally unrelated agents, a phenomenon known as multidrug resistance, MDR. The purpose of this study is to investigate cell growth inhibition of wild type and the corresponding MDR cells by Tumor Treating Fields - TTFields, a new cancer treatment modality that is free of systemic toxicity. The TTFields were applied alone and in combination with paclitaxel and doxorubicin. Three pairs of wild type/MDR cell lines, having resistivity resulting from over-expression of ABC transporters, were studied: a clonal derivative (C11) of parental Chinese hamster ovary AA8 cells and their emetine-resistant sub-line Emt R1 ; human breast cancer cells MCF-7 and their mitoxantrone-resistant sub lines MCF-7/Mx and human breast cancer cells MDA-MB-231 and their doxorubicin resistant MDA-MB-231/Dox cells. TTFields were applied for 72 hours with and without the chemotherapeutic agents. The numbers of viable cells in the treated cultures and the untreated control groups were determined using the XTT assay. Student t-test was applied to asses the significance of the differences between results obtained for each of the three cell pairs. TTFields caused a similar reduction in the number of viable cells of wild type and MDR cells. Treatments by TTFields/drug combinations resulted in a similar increased reduction in cell survival of wild type and MDR cells. TTFields had no effect on intracellular doxorubicin accumulation in both wild type and MDR cells. The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors

Reações tegumentares adversas relacionadas aos agentes antineoplásicos: parte II Adverse mucocutaneous reactions related to chemotherapeutic agents: part II

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Paulo Ricardo Criado

2010-10-01

Full Text Available Os eventos e reações envolvendo quimioterapia são frequentes na prática oncológica. Agentes quimioterápicos são uma modalidade de tratamento amplamente utilizada. Efeitos colaterais podem variar de frequência e também ser confundidos com outras manifestações tegumentares do tratamento oncológico. Este artigo objetiva expor as informações sobre reações cutâneas à quimioterapia, em especial, aqueles para os quais o dermatologista é requisitado a emitir parecer e a comentar sobre a segurança e a viabilidade da readministração de uma droga específica. Os autores descrevem os aspectos associados a esses eventos, fazendo uma análise detalhada de cada um deles.Events and reactions involving chemotherapy are common in clinical oncology. Chemotherapeutic agents are widely used in therapy. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from the oncological treatment. The objective of this paper was to present data on skin reactions to chemotherapy, particularly those cases in which the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. The authors describe aspects associated with these events, presenting a detailed analysis of each one of them.

Chemotherapy Agents: A Primer for the Interventional Radiologist

OpenAIRE

Mihlon, Frank; Ray, Charles E.; Messersmith, Wells

2010-01-01

In this article, the authors review the basic principles of cancer chemotherapy and provide an overview of each of the general classes of chemotherapeutic agents with a target audience of interventional radiologists in mind. Special attention is paid to agents used in regional chemotherapy as well as agents commonly included in systemic chemotherapeutic regimens for patients who also require regional chemotherapy.

A monofunctional platinum complex coordinated to a rhodium metalloinsertor selectively binds mismatched DNA in the minor groove.

Science.gov (United States)

Weidmann, Alyson G; Barton, Jacqueline K

2015-10-05

We report the synthesis and characterization of a bimetallic complex derived from a new family of potent and selective metalloinsertors containing an unusual Rh-O axial coordination. This complex incorporates a monofunctional platinum center containing only one labile site for coordination to DNA, rather than two, and coordinates DNA nonclassically through adduct formation in the minor groove. This conjugate displays bifunctional, interdependent binding of mismatched DNA via metalloinsertion at a mismatch as well as covalent platinum binding. DNA sequencing experiments revealed that the preferred site of platinum coordination is not the traditional N7-guanine site in the major groove, but rather N3-adenine in the minor groove. The complex also displays enhanced cytotoxicity in mismatch repair-deficient and mismatch repair-proficient human colorectal carcinoma cell lines compared to the chemotherapeutic cisplatin, and it triggers cell death via an apoptotic pathway, rather than the necrotic pathway induced by rhodium metalloinsertors.

Urinary excretion of platinum, arsenic and selenium of cancer patients from the Antofagasta region in Chile treated with platinum-based drugs

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Román Domingo A

2012-04-01

Full Text Available Abstract Background Arsenic exposure increases the risk of non-cancerous and cancerous diseases. In the Antofagasta region in Chile, an established relationship exists between arsenic exposure and the risk of cancer of the bladder, lung and skin. Platinum-based drugs are first-line treatments, and many works recognise selenium as a cancer-fighting nutrient. We characterised the short-term urinary excretion amounts of arsenic, selenium and platinum in 24-h urine samples from patients with lung cancer and those with cancer other than lung treated with cisplatin or/and carboplatin. As - Se - Pt inter-element relationships were also investigated. Results The amounts of platinum excreted in urine were not significantly different between patients with lung cancer and those with other cancers treated with cisplatin, despite the significant variation in platinum amounts supplied from platinum-based drugs. In general, the analytical amounts of excreted selenium were greater than those for arsenic, which could imply that platinum favours the excretion of selenium. For other types of cancers treated with drugs without platinum, excretion of selenium was also greater than that of arsenic, suggesting an antagonist selenium-anti-cancer drug relationship. Conclusions Regards the baseline status of patients, the analytical amounts of excreted Se is greater than those for As, particularly, for cisplatin chemotherapy. This finding could imply that for over the As displacement Pt favours the excretion of Se. The analytical amounts of excreted Se were greater than those for As, either with and without Pt-containing drugs, suggesting an antagonist Se-anti-cancer drug relationship. However, it seemed that differences existed between As - Se - Pt inter-element associations in patients treated for lung cancer in comparison with those treated for cancer other than lung. Therefore, knowledge obtained in this work, can contribute to understanding the arsenic cancer

Studies on uptake and distribution of chemotherapeutic agents to malignant tumors of the head and neck in rabbits, 2

International Nuclear Information System (INIS)

Yamada, Ryuichi

1981-01-01

Experiments were performed to investigate incorporation and distribution of chemotherapeutic agents into malignant tumors of the head and neck by microautoradiographic and electron microscopic-autoradiographic observations of VX2 carcinoma transplanted in the lower genial region of rabbits after injection of 3 H-Adriamycin as a tracer. The following findings were obtained. 1. On microautoradiograms, 3 H-Adriamycin was distributed predominantly in the nucleoplasm, rather than in the cytoplasm, of tumor tissues. 2. At the ultrastructural level, 3 H-Adriamycin was localized in the nuclear membrane and nucleoli within the nucleoplasm and in the rough endoplasmic reticulum and secretory granules within the cytoplasm. 3. These findings seem to indicate that Adriamycin may inhibit the synthesis of DNA and RNA in the nucleoplasm. (author)

Synergistic Effects of Secretory Phospholipase A2 from the Venom of Agkistrodon piscivorus piscivorus with Cancer Chemotherapeutic Agents

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Jennifer Nelson

2013-01-01

Full Text Available Healthy cells typically resist hydrolysis catalyzed by snake venom secretory phospholipase A2. However, during various forms of programmed cell death, they become vulnerable to attack by the enzyme. This observation raises the question of whether the specificity of the enzyme for dying cells could be used as a strategy to eliminate tumor cells that have been intoxicated but not directly killed by chemotherapeutic agents. This idea was tested with S49 lymphoma cells and a broad range of antineoplastic drugs: methotrexate, daunorubicin, actinomycin D, and paclitaxel. In each case, a substantial population of treated cells was still alive yet vulnerable to attack by the enzyme. Induction of cell death by these agents also perturbed the biophysical properties of the membrane as detected by merocyanine 540 and trimethylammonium-diphenylhexatriene. These results suggest that exposure of lymphoma cells to these drugs universally causes changes to the cell membrane that render it susceptible to enzymatic attack. The data also argue that the snake venom enzyme is not only capable of clearing cell corpses but can aid in the demise of tumor cells that have initiated but not yet completed the death process.

Genome-wide local ancestry approach identifies genes and variants associated with chemotherapeutic susceptibility in African Americans.

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Heather E Wheeler

Full Text Available Chemotherapeutic agents are used in the treatment of many cancers, yet variable resistance and toxicities among individuals limit successful outcomes. Several studies have indicated outcome differences associated with ancestry among patients with various cancer types. Using both traditional SNP-based and newly developed gene-based genome-wide approaches, we investigated the genetics of chemotherapeutic susceptibility in lymphoblastoid cell lines derived from 83 African Americans, a population for which there is a disparity in the number of genome-wide studies performed. To account for population structure in this admixed population, we incorporated local ancestry information into our association model. We tested over 2 million SNPs and identified 325, 176, 240, and 190 SNPs that were suggestively associated with cytarabine-, 5'-deoxyfluorouridine (5'-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-4. Importantly, some of these variants are found only in populations of African descent. We also show that cisplatin-susceptibility SNPs are enriched for carboplatin-susceptibility SNPs. Using a gene-based genome-wide association approach, we identified 26, 11, 20, and 41 suggestive candidate genes for association with cytarabine-, 5'-DFUR-, carboplatin-, and cisplatin-induced cytotoxicity, respectively (p≤10(-3. Fourteen of these genes showed evidence of association with their respective chemotherapeutic phenotypes in the Yoruba from Ibadan, Nigeria (p<0.05, including TP53I11, COPS5 and GAS8, which are known to be involved in tumorigenesis. Although our results require further study, we have identified variants and genes associated with chemotherapeutic susceptibility in African Americans by using an approach that incorporates local ancestry information.

Radiation and platinum drug interaction

International Nuclear Information System (INIS)

Nias, A.H.W.

1985-01-01

The ideal platinum drug-radiation interaction would achieve radiosensitization of hypoxic tumour cells with the use of a dose of drug which is completely non-toxic to normal tissues. Electron-affinic agents are employed with this aim, but the commoner platinum drugs are only weakly electron-affinic. They do have a quasi-alkylating action however, and this DNA targeting may account for the radiosensitizing effect which occurs with both pre- and post-radiation treatments. Because toxic drug dosage is usually required for this, the evidence of the biological responses to the drug and to the radiation, as well as to the combination, requires critical analysis before any claim of true enhancement, rather than simple additivity, can be accepted. The amount of enhancement will vary with both the platinum drug dose and the time interval between drug administration and radiation. Clinical schedules may produce an increase in tumour response and/or morbidity, depending upon such dose and time relationships. (author)

Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

Science.gov (United States)

Tsen, Andrew R; Long, Patrick M; Driscoll, Heather E; Davies, Matthew T; Teasdale, Benjamin A; Penar, Paul L; Pendlebury, William W; Spees, Jeffrey L; Lawler, Sean E; Viapiano, Mariano S; Jaworski, Diane M

2014-03-15

Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA-induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors. © 2013 UICC.

Characteristics improvement of hydrophobic polytetrafluoroethylene-platinum catalysts for tritium separation

International Nuclear Information System (INIS)

Popescu, I.; Ionita, Gh.; Dobrinescu, D.; Varlam, C.; Stefanescu, I.

2006-01-01

Full text: Based on the long experience of the authors in the preparation, testing and evaluation of the performances of hydrophobic catalysts and based on the reviewed references, this paper presents up-to-date R and D activities on the preparation methods and applications of the hydrophobic catalysts in tritium separation. The objectives of the paper are: how to improve the characteristics and performance of platinum hydrophobic catalysts; to assess and find a new procedure for the preparation of a new improved hydrophobic catalyst. From reviewed references one can conclude that platinum is the most active and efficient catalytic metal while the polytetrafluoroethylene is the best wet-proofing agent. A new improved hydrophobic Pt-catalyst has been proposed and its testing is now underway. The main steps and experimental conditions of preparation are thoroughly discussed. A new wet-proofing agent and new binders (titanium dioxide, cerium dioxide, zirconium dioxide) with a catalytic role are proposed and tested. The physico-structural parameters of the improved catalyst have been determined and are discussed in detail. The new proposal is a promising idea to improve the performance of conventional hydrophobic Pt-catalysts. (authors)

A novel chemotherapeutic sensitivity-testing system based on collagen gel droplet embedded 3D-culture methods for hepatocellular carcinoma.

Science.gov (United States)

Hou, Jun; Hong, Zhixian; Feng, Fan; Chai, Yantao; Zhang, Yunkai; Jiang, Qiyu; Hu, Yan; Wu, Shunquan; Wu, Yingsong; Gao, Xunian; Chen, Qiong; Wan, Yong; Bi, Jingfeng; Zhang, Zheng

2017-11-08

Patients suffering from advanced stage hepatocellular carcinoma (HCC) often exhibit a poor prognosis or dismal clinical outcomes due to ineffective chemotherapy or a multi-drug resistance (MDR) process. Thus, it is urgent to develop a new chemotherapeutic sensitivity testing system for HCC treatment. The presence study investigated the potential application of a novel chemotherapeutic sensitivity-testing system based on a collagen gel droplet embedded 3D-culture system (CD-DST). Primary cells were separating from surgical resection specimens and then tested by CD-DST. To identify whether HCC cell lines or cells separating from clinical specimens contain MDR features, the cells were treated with an IC 50 (half maximal inhibitory concentration) or IC max (maximal inhibitory concentration) concentration of antitumor agents, e.g., 5-furuolouracil (5-FU), paclitaxel (PAC), cisplatin (CDDP), epirubicin (EPI), or oxaliplatin (L-OHP), and the inhibitory rates (IRs) were calculated. HepG2 cells were sensitive to 5-FU, PAC, CDDP, EPI, or L-OHP; the IC 50 value is 0.83 ± 0.45 μg/ml, 0.03 ± 0.02 μg/ml, 1.15 ± 0.75 μg/ml, 0.09 ± 0.03 μg/ml, or 1.76 ± 0.44 μg/ml, respectively. Only eight (8/26), nine (9/26), or five (5/26) patients were sensitive to the IC max concentration of CDDP, EPI, or L-OHP; whereas only three (3/26), four (4/26), or two (2/26) patients were sensitive to the IC 50 concentration of CDDP, EPI, or L-OHP. No patients were sensitive to 5-FU or PAC. The in vitro drug sensitivity exanimation revealed the MDR features of HCC and examined the sensitivity of HCC cells from clinical specimens to anti-tumor agents. CD-DST may be a useful method to predict the potential clinical benefits of anticancer agents for HCC patients.

Biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy

DEFF Research Database (Denmark)

Stenvang, Jan; Kümler, Iben; Nygård, Sune Boris

2013-01-01

-standard chemotherapeutic drug will be relatively low in such a patient cohort it is a pre-requisite that such testing is based on predictive biomarkers. This review describes our strategy of biomarker-guided repurposing of chemotherapeutic drugs for cancer therapy, taking the repurposing of topoisomerase I (Top1...

Schiff base-Poloxamer P85 combination demonstrates chemotherapeutic effect on prostate cancer cells in vitro.

Science.gov (United States)

Demirci, Selami; Doğan, Ayşegül; Türkmen, Neşe Başak; Telci, Dilek; Rizvanov, Albert A; Şahin, Fikrettin

2017-02-01

Prostate cancer is a multistep and complicated cancer type that is regulated by androgens at the cellular level and remains the second commonest cause of death among men. Discovery and development of novel chemotherapeutic agents enabling rapid tumor cell death with minimal toxic effects to healthy tissues might greatly improve the safety of chemotherapy. The present study evaluates the anti-cancer activity of a novel heterodinuclear copper(II)Mn(II) complex (Schiff base) in combination with poly(ethylene oxide) and poly(propylene oxide) block copolymer (Pluronic) P85. We used assays for cell proliferation, apoptosis, cell migration and invasion, DNA binding and cleavage to elucidate the molecular mechanisms of action, in addition to the anti-inflammatory potency of the new combination. The combined treatment of Schiff base and P85 lead to a remarkable anti-cancer effect on prostate cancer cell lines. Cell proliferation was inhibited in Schiff base-P85 treatment. The activity of this formulation is on DNA binding and cleavage and prevents inflammation in in vitro conditions. This is the first study presenting the anti-cancer activity of the present Schiff base derivative and its combination with P85 to treat prostate cancer in vitro. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis

OpenAIRE

Wang, Ying; Rishi, Arun K.; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I.; Wali, Anil

2011-01-01

Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has...

Use of the dog spleen for studying effects of irradiation and chemotherapeutic agents, with suggested uses of other organs

International Nuclear Information System (INIS)

Wilcox, L.D.; De Rose, G.; Cooke, D.

1976-01-01

The irradiation of the exteriorized spleen of the dog, with the animal lead-shielded, produced constant changes in the white blood cells. The time of recovery from the irradiation effect was determined. The normal canine spleen could handle live pneumococci injected into the splenic artery, as proven by sterile cultures of splenic vein samples. The size of the bolus used was determined by repeated trials and proved to be one billion pneumococci per pound of body weight. The capacity of the irradiated spleen to handle this number of pneumococci was impaired. It was found that whole body irradiation, nitrogen mustard, thio-tepa, cyclophosphamide, methotrexate, 5-fluorouracil, vinblastine, and azothioprine all impaired this capacity of the spleen. The dose of the chemotherapeutic agent was the same in milligrams per kilogram as that used in the cancer clinic. A method for determining the recovery time following the use of one or more agents was developed with the repeated use of the spleen model. By extending the methods used with the spleen it was found that similar use could be made, usually without surgery, of the liver, gut, and lungs

Effect of mutagens, chemotherapeutic agents and defects in DNA repair genes on recombination in F' partial diploid Escherichia coli

International Nuclear Information System (INIS)

Norin, A.J.; Goldschmidt, E.P.

1979-01-01

The ability of mutagenic agents, nonmutagenic substances and defects in DNA repair to alter the genotype of F' partial diploid (F30) Escherichia coli was determined. The frequency of auxotrophic mutants and histidine requiring (His - ) haploid colonies was increased by mutagen treatment but Hfr colonies were not detected in F30 E. coli even with specific selection techniques. Genotype changes due to nonreciprocal recombination were determined by measuring the frequency of His - homogenotes, eg. F' hisC780, hisI + /hisC780, hisI + , arising from a His + heterogenote, F' hisC780 hisI + /hisC + , his1903. At least 75% of the recombinants were homozygous for histidine alleles which were present on the F' plasmid (exogenote) of the parental hetergenote rather than for histidine alleles on the chromosome. Mutagens, chemotherapeutic agents which block DNA synthesis and a defective DNA polymerase I gene, polA1, were found to increase the frequency of nonreciprocal recombination. A defect in the ability to excise thymine dimers, uvrC34, did not increase spontaneous nonreciprocal recombination. However, UV irradiation but not methyl methanesulfonate (MMS) induced greater recombination in this excision-repair defective mutant than in DNA-repair-proficient strains. (Auth.)

The cell's nucleolus: an emerging target for chemotherapeutic intervention.

Science.gov (United States)

Pickard, Amanda J; Bierbach, Ulrich

2013-09-01

The transient nucleolus plays a central role in the up-regulated synthesis of ribosomal RNA (rRNA) to sustain ribosome biogenesis, a hallmark of aberrant cell growth. This function, in conjunction with its unique pathohistological features in malignant cells and its ability to mediate apoptosis, renders this sub-nuclear structure a potential target for chemotherapeutic agents. In this Minireview, structurally and functionally diverse small molecules are discussed that have been reported to either interact with the nucleolus directly or perturb its function indirectly by acting on its dynamic components. These molecules include all major classes of nucleic-acid-targeted agents, antimetabolites, kinase inhibitors, anti-inflammatory drugs, natural product antibiotics, oligopeptides, as well as nanoparticles. Together, these molecules are invaluable probes of structure and function of the nucleolus. They also provide a unique opportunity to develop novel strategies for more selective and therefore better-tolerated chemotherapeutic intervention. In this regard, inhibition of RNA polymerase-I-mediated rRNA synthesis appears to be a promising mechanism for killing cancer cells. The recent development of molecules targeted at G-quadruplex-forming rRNA gene sequences, which are currently undergoing clinical trials, seems to attest to the success of this approach. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparison of different sample preparation methods for platinum determination in cultured cells by graphite furnace atomic absorption spectrometry

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Man Xiao

2017-01-01

Full Text Available Background Platinum-based agents are widely used in chemotherapy against solid tumors and insufficient intracellular drug accumulation is one of the leading causes of platinum resistance which is associated with poor survival of tumor patients. Thus, the detection of intracellular platinum is pivotal for studies aiming to overcome platinum resistance. In the present study, we aimed to establish a reliable graphite furnace atomic absorption spectrometry (GFAAS-based assay to quantify the intracellular platinum content for cultured cells. Methods Several most commonly applied cell preparation methods, including 0.2% HNO3, 0.2% Triton X-100, concentrated nitric acid, RIPA combined with concentrated nitric acid and hydroxide, followed by GFAAS for platinum detection were compared in ovarian, cervical and liver cancer cell lines to obtain the optimal one, and parameters regarding linearity, accuracy, precision and sensitivity were evaluated. Influence of other metals on platinum detection and the storage conditions of samples were also determined. Results The treatment of cells with 0.2% HNO3 was superior to other approaches with fewer platinum loss and better repeatability. The recovery rate and precision of this method were 97.3%–103.0% and 1.4%–3.8%, respectively. The average recoveries in the presence of other metals were 95.1%–103.1%. The detection limit was 13.23 ug/L. The recovery rate of platinum remained acceptable even in cell samples stored in −20 °C or −80 °C for two months. Discussion After comparison, we found that 0.2% HNO3 was optimal for intracellular platinum quantification based on GFAAS, which presented values compatible with that of inductively-coupled plasma mass-spectrometry (ICP-MS, and this is partially attributed to the simplicity of this method. Moreover, the assay was proved to be accurate, sensitive, cost-effective and suitable for the research of platinum-based antitumor therapy.

Ixabepilone: a new chemotherapeutic option for refractory metastatic breast cancer

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Shannon Puhalla

2008-09-01

Full Text Available Shannon Puhalla, Adam BrufskyUPMC Magee-Womens Cancer Program, University of Pittsburgh, Pittsburgh, Pennsylvania, USAAbstract: Taxane therapy is commonly used in the treatment of metastatic breast cancer. However, most patients will eventually become refractory to these agents. Ixabepilone is a newly approved chemotherapeutic agent for the treatment of metastatic breast cancer. Although it targets microtubules similarly to docetaxel and paclitaxel, ixabepilone has activity in patients that are refractory to taxanes. This review summarizes the pharmacology of ixapebilone and clinical trials with the drug both as a single agent and in combination. Data were obtained using searches of PubMed and abstracts of the annual meetings of the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium from 1995 to 2008. Ixapebilone is a semi-synthetic analog of epothilone B that acts to induce apoptosis of cancer cells via the stabilization of microtubules. Phase I clinical trials have employed various dosing schedules ranging from daily to weekly to 3-weekly. Dose-limiting toxicites included neuropathy and neutropenia. Responses were seen in a variety of tumor types. Phase II studies verified activity in taxane-refractory metastatic breast cancer. The FDA has approved ixabepilone for use as monotherapy and in combination with capecitabine for the treatment of metastatic breast cancer. Ixabepilone is an efficacious option for patients with refractory metastatic breast cancer. The safety profile is similar to that of taxanes, with neuropathy and neutropenia being dose-limiting. Studies are ongoing with the use of both iv and oral formulations and in combination with other chemotherapeutic and biologic agents.Keywords: ixabepilone, epothilone, metastatic breast cancer, taxane-refractory

A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

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Fangping Li

2018-03-01

Full Text Available Sepia ink polysaccharide (SIP isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami, cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents.

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided versus empirical chemotherapy in unresectable non-small cell lung cancer.

Science.gov (United States)

Moon, Yong Wha; Sohn, Joo Hyuk; Kim, Yong Tai; Chang, Hyun; Jeong, Jae Heon; Lee, Young Joo; Chang, Joon; Kim, Se Kyu; Jung, Minkyu; Hong, Soojung; Choi, Sung Ho; Kim, Joo-Hang

2009-10-01

We retrospectively compared adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided and empirical chemotherapies for unresectable non-small cell lung cancer (NSCLC) in this case-control study. Unresectable NSCLC patients receiving ATP-CRA-guided platinum-based doublets as first-line therapy were enrolled as cases (n=27; 14 platinum-sensitive and 13 platinum-resistant patients). Performance status, stage, and chemotherapeutic regimen-matched patients receiving empirical chemotherapy were selected from the retrospective database as controls (n=93) in a case to control ratio of approximately 1:3. Response rate and survival (progression-free; overall) in both groups were not significantly different. However, the platinum-sensitive subgroup by ATP-CRA showed a higher response rate than the empirical group (71 versus 38%; p=0.023) with a trend toward longer progression-free survival (8.7 versus 4.8 months for platinum-sensitive versus empirical; p=0.223) and overall survival (not reached versus 12.6 months for platinum-sensitive versus empirical for p=0.134). ATP-CRA may be helpful in selecting platinum-responsive patients in unresectable NSCLC. We consider that nonplatinum doublets in platinum-resistant patients by ATP-CRA may be a more adapted approach than platinum-based doublets in future clinical trials.

para-Sulfonatocalix[4]arene and polyamidoamine dendrimer nanocomplexes as delivery vehicles for a novel platinum anticancer agent.

Science.gov (United States)

Pang, Chi Ting; Ammit, Alaina J; Ong, Yu Qing Elysia; Wheate, Nial J

2017-11-01

Novel para-sulfonatocalix[4]arene (sCX[4]) and polyamidoamine (PAMAM) dendrimer nanocomplexes were evaluated as delivery vehicles for the platinum anticancer agent [(1,10-phenanthroline)(1S,2S-diaminocyclohexane)platinum(II)] chloride (PHENSS). Different ratios of sCX[4] to PHENSS were tested for their compatibility, with a ratio of 6:1 sCX[4]:PHENSS having the best solubility. The loading of sCX[4], and sCX[4]-bound PHENSS, onto three different generations of PAMAM dendrimers (G3.0-5.0) was examined using UV-visible spectrophotometry. The quantity of sCX[4] bound was found to increase exponentially with dendrimer size: G3, 15 sCX[4] molecules per dendrimer; G4, 37; and G5, 78. Similarly, the loading of sCX[4]-bound PHENSS also increased with increasing dendrimer size: G3, 7 PHENSS molecules per dendrimer; G4, 14; and G5, 28.5. The loading of sCX[4]-bound PHENSS molecules is significantly lower when compared with that of sCX[4], which indicates that less than half of the binding sites were occupied (45, 44, and 44%, respectively). By 1 H NMR and UV-vis analysis, the nanocomplex was found to be stable in NaCl solutions at concentrations up to 150mM. While PHENSS is more active in vitro than cisplatin against the human breast cancer cell line, MCF-7, delivery of PHENSS using the sCX[4]-dendrimer nanocomplexes, regardless of dendrimer generation, had little effect on PHENSS cytotoxicity. The results of this study may have application in the delivery of a variety of small molecule metal-based drugs for which chemical conjugation to a nanoparticle is undesired or not feasible. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficient light-emitting devices based on platinum-complexes-anchored polyhedral oligomeric silsesquioxane materials

KAUST Repository

Yang, Xiaohui

2010-08-24

The synthesis, photophysical, and electrochemical characterization of macromolecules, consisting of an emissive platinum complex and carbazole moieties covalently attached to a polyhedral oligomeric silsesquioxane (POSS) core, is reported. Organic light-emitting devices based on these POSS materials exhibit a peak external quantum efficiency of ca. 8%, which is significantly higher than that of the analogous devices with a physical blend of the platinum complexes and a polymer matrix, and they represent noticeable improvement in the device efficiency of solution-processable phosphorescent excimer devices. Furthermore, the ratio of monomer and excimer/aggregate electroluminescent emission intensity, as well as the device efficiency, increases as the platinum complex moiety presence on the POSS macromolecules decreases. © 2010 American Chemical Society.

DNA interaction with platinum-based cytostatics revealed by DNA sequencing.

Science.gov (United States)

Smerkova, Kristyna; Vaculovic, Tomas; Vaculovicova, Marketa; Kynicky, Jindrich; Brtnicky, Martin; Eckschlager, Tomas; Stiborova, Marie; Hubalek, Jaromir; Adam, Vojtech

2017-12-15

The main mechanism of action of platinum-based cytostatic drugs - cisplatin, oxaliplatin and carboplatin - is the formation of DNA cross-links, which restricts the transcription due to the disability of DNA to enter the active site of the polymerase. The polymerase chain reaction (PCR) was employed as a simplified model of the amplification process in the cell nucleus. PCR with fluorescently labelled dideoxynucleotides commonly employed for DNA sequencing was used to monitor the effect of platinum-based cytostatics on DNA in terms of decrease in labeling efficiency dependent on a presence of the DNA-drug cross-link. It was found that significantly different amounts of the drugs - cisplatin (0.21 μg/mL), oxaliplatin (5.23 μg/mL), and carboplatin (71.11 μg/mL) - were required to cause the same quenching effect (50%) on the fluorescent labelling of 50 μg/mL of DNA. Moreover, it was found that even though the amounts of the drugs was applied to the reaction mixture differing by several orders of magnitude, the amount of incorporated platinum, quantified by inductively coupled plasma mass spectrometry, was in all cases at the level of tenths of μg per 5 μg of DNA. Copyright © 2017 Elsevier Inc. All rights reserved.

Preparation of Carbon-Platinum-Ceria and Carbon-Platinum-Cerium catalysts and its application in Polymer Electrolyte Fuel Cell: Hydrogen, Methanol, and Ethanol

Science.gov (United States)

Guzman Blas, Rolando Pedro

This thesis is focused on fuel cells using hydrogen, methanol and ethanol as fuel. Also, in the method of preparation of catalytic material for the anode: Supercritical Fluid Deposition (SFD) and impregnation method using ethylenediaminetetraacetic acid (EDTA) as a chelating agent. The first part of the thesis describes the general knowledge about Hydrogen Polymer Exchange Membrane Fuel Cell (HPEMFC),Direct Methanol Fuel Cell (DMFC) and Direct Ethanol Fuel Cell (DEFC), as well as the properties of Cerium and CeO2 (Ceria). The second part of the thesis describes the preparation of catalytic material by Supercritical Fluid Deposition (SFD). SFD was utilized to deposit Pt and ceria simultaneously onto gas diffusion layers. The Pt-ceria catalyst deposited by SFD exhibited higher methanol oxidation activity compared to the platinum catalyst alone. The linear sweep traces of the cathode made for the methanol cross over study indicate that Pt-Ceria/C as the anode catalyst, due to its better activity for methanol, improves the fuel utilization, minimizing the methanol permeation from anode to cathode compartment. The third and fourth parts of the thesis describe the preparation of material catalytic material Carbon-Platinum-Cerium by a simple and cheap impregnation method using EDTA as a chelating agent to form a complex with cerium (III). This preparation method allows the mass production of the material catalysts without additional significant cost. Fuel cell polarization and power curves experiments showed that the Carbon-Platinum-Cerium anode materials exhibited better catalytic activity than the only Vulcan-Pt catalysts for DMFC, DEFC and HPEMFC. In the case of Vulcan-20%Pt-5%w Cerium, this material exhibits better catalytic activity than the Vulcan-20%Pt in DMFC. In the case of Vulcan-40% Pt-doped Cerium, this material exhibits better catalytic activity than the Vulcan-40% Pt in DMFC, DEFC and HPEMFC. Finally, I propose a theory that explains the reason why the

Study of Auger effect in DNA when bound to molecules containing platinum. A possible application to hadrontherapy

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, K.; Usami, N.; Sasaki, I.; Frohlich, H.; Le Sech, C. E-mail: lesech@lcam.u-psud.fr

2003-01-01

Complexes made of DNA and Cyclo-Pt bound to plasmid DNA, were placed in aqueous solution and irradiated with monochromatic X-rays in the range E=8.5-13 keV, including the resonant photoabsorption energy of the L{sub III} shell of the platinum atom. The number of single- and double-strand breaks (ssb and dsb) induced by irradiation on a supercoiled DNA plasmid was measured by the production of circular-nicked and linear forms. In order to disentangle the contribution of the direct effects imparted to ionization, and the indirect effects due to a free radical attack, experiments have been performed in the presence of a small concentration (64 mmol l{sup -1}) of hydroxyl free radical scavenger dimethyl sulfoxide (DMSO). An enhancement of the number of ssb and dsb is observed when the plasmids contain the Pt intercalating molecules. Even when off-resonant X-rays are used, the strand break efficiency remains higher than expected based upon the absorption cross-section, as if the Pt bound to DNA is increasing the yield of strand breaks. A mechanism is suggested, involving photoelectrons generated from the ionization of water which efficiently ionize Pt atoms. This observation may provide an insight to understanding the effects of new radiotherapy protocols, associated chemotherapeutic agents such as cisplatin and ordinary radiotherapy for tumoral treatments.

Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

Directory of Open Access Journals (Sweden)

Chung Jae

2009-06-01

pathways was observed during development of platinum resistance in ovarian cancer. Integrated analysis of DNA methylation and gene expression may allow for the identification of new therapeutic targets and/or biomarkers prognostic of disease response. Finally, our results suggest that epigenetic therapies may facilitate the prevention or reversal of transcriptional repression responsible for chemoresistance and the restoration of sensitivity to platinum-based chemotherapeutics.

Strategies for improving chemotherapeutic delivery to solid tumors mediated by vascular permeability modulation

Science.gov (United States)

Roy Chaudhuri, Tista

An essential mode of distribution of blood-borne chemotherapeutic agents within a solid tumor is via the micro-circulation. Poor tumor perfusion, because of a lack of functional vasculature or a lack of microvessels, as well as low tumor vascular permeability, can prevent adequate deposition of even low molecular-weight agents into the tumor. The modulation of tumor vascular function and density can provides numerous strategies for improving intratumor deposition of chemotherapeutic agents. Here we investigated strategies to improve drug delivery to two tumor types that share in common poor drug delivery, but differ in the underlying cause. First, in an angiogenesis-driven brain tumor model of Glioblastoma, the vascular permeability barrier, along with poorly-functional vasculature, hinders drug delivery. A strategy of nanoparticle-based tumor 'priming' to attack the vascular permeability barrier, employing sterically stabilized liposomal doxorubicin (SSL-DXR), was investigated. Functional and histological evaluation of tumor vasculature revealed that after an initial period of depressed vascular permeability and vascular pruning 3--4 days after SSL-DXR administration, vascular permeability and perfusion were restored and then elevated after 5--7 days. As a result of tumor priming, deposition of subsequently-administered nanoparticles was enhanced, and the efficacy of temozolomide (TMZ), if administered during the window of elevated permeability, was increased. The sequenced regimen resulted in a persistent reduction of the tumor proliferative index and a 40% suppression of tumor volume, compared to animals that received both agents simultaneously. Second, in a hypovascular, pancreatic ductal adenocarcinoma model, disruption of tumor-stromal communication via sonic hedgehog (sHH) signaling pathway inhibition mediated an indirect vascular proliferation and a more than 2-fold increase in intratumor nanoparticle deposition. Enhanced delivery of SSL-DXR in tumors pre

Acute cold hypersensitivity characteristically induced by oxaliplatin is caused by the enhanced responsiveness of TRPA1 in mice

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Zhao Meng

2012-07-01

Full Text Available Abstract Background Oxaliplatin, a platinum-based chemotherapeutic agent, causes an unusual acute peripheral neuropathy. Oxaliplatin-induced acute peripheral neuropathy appears in almost all patients rapidly after infusion, and is triggered or exacerbated by cold, while its mechanisms are poorly understood. In this study, the involvement of thermosensitive transient receptor potential channels (TRPA1, TRPM8 and TRPV1 in oxaliplatin-induced acute hypersensitivity was investigated in mice. Results A single intraperitoneal administration of oxaliplatin (1–10 mg/kg induced cold but not mechanical hypersensitivity within 2 h in a dose-dependent manner. Infusion of the oxaliplatin metabolite, oxalate (1.7 mg/kg, also induced acute cold hypersensitivity, while another platinum-based chemotherapeutic agent, cisplatin (5 mg/kg, or the non-platinum-containing chemotherapeutic agent, paclitaxel (6 mg/kg failed to induce mechanical or cold hypersensitivity. The oxaliplatin-induced acute cold hypersensitivity was abolished by the TRPA1 antagonist HC-030031 (100 mg/kg and by TRPA1 deficiency. The nocifensive behaviors evoked by intraplantar injections of allyl-isothiocyanate (AITC; TRPA1 agonist were significantly enhanced in mice treated for 2 h with oxaliplatin (1–10 mg/kg in a dose-dependent manner, while capsaicin (TRPV1 agonist-evoked nocifensive behaviors were not affected. Menthol (TRPM8/TRPA1 agonist-evoked nocifensive-like behaviors were also enhanced by oxaliplatin pretreatment, which were inhibited by TRPA1 deficiency. Similarly, oxalate enhanced, but neither cisplatin nor paclitaxel affected AITC-evoked nocifensive behaviors. Pretreatment of cultured mouse dorsal root ganglia (DRG neurons with oxaliplatin (30–300 μM for 1, 2, or 4 h significantly increased the number of AITC-sensitive neurons in a concentration-dependent manner whereas there was no change in the number of menthol- or capsaicin-sensitive neurons

Redeposition of electrochemically dissolved platinum as nanoparticles on carbon

DEFF Research Database (Denmark)

Norgaard, C. F.; Stamatin, S. N.; Skou, E. M.

2014-01-01

communication reports a simple chemical method for reprecipitating platinum as nanoparticles of reasonable particle size on a carbon substrate without intermediary separation and handling of solid platinum salt. After electrochemical dissolution, platinum was reprecipitated using a polyol based method. Platinum...

Lipid solubility of the platinum group metals Pt, Pd and Rh in dependence on the presence of complexing agents

International Nuclear Information System (INIS)

Zimmermann, Sonja; Menzel, Christoph M.; Stueben, Doris; Taraschewski, Horst; Sures, Bernd

2003-01-01

All complexing agents had a significant influence on octanol solubility of PGM. - Investigations on the bioaccumulation of the platinum group metals (PGM) Pt, Pd and Rh in aquatic organisms are of growing interest in environmental research due to the increasing emission of these metals by motor vehicles with catalytic converters. Until now, nothing is known about the possible influence of complexing agents on the bioaccumulation capacity of these precious metals. According to the partition coefficient between 1-octanol and water (P OW ) as a measure of bioaccumulation, in this study a simple shaking method was performed in order to investigate the effects of different complexing agents (L-methionine, thio urea, EDTA, humic substances, bile compounds) on the octanol solubility of the PGM. The results demonstrated a significant influence of all agents used. L-Methionine and thio urea decreased the lipid solubility. In contrast, the presence of EDTA, humic substances and especially bile caused a higher transfer of metals in the octanol phase. For most complexing agents tested, the transfer of Pd to the lipid phase was significantly higher compared with Rh and Pt, except for bile acid where the highest octanol solubility was found for Pt. Recent experimental results on PGM accumulation in zebra mussels confirm a high bioaccumulation of Pd which could be predicted from the lipid solubility

Lipid solubility of the platinum group metals Pt, Pd and Rh in dependence on the presence of complexing agents

Energy Technology Data Exchange (ETDEWEB)

Zimmermann, Sonja; Menzel, Christoph M.; Stueben, Doris; Taraschewski, Horst; Sures, Bernd

2003-07-01

All complexing agents had a significant influence on octanol solubility of PGM. - Investigations on the bioaccumulation of the platinum group metals (PGM) Pt, Pd and Rh in aquatic organisms are of growing interest in environmental research due to the increasing emission of these metals by motor vehicles with catalytic converters. Until now, nothing is known about the possible influence of complexing agents on the bioaccumulation capacity of these precious metals. According to the partition coefficient between 1-octanol and water (P{sub OW}) as a measure of bioaccumulation, in this study a simple shaking method was performed in order to investigate the effects of different complexing agents (L-methionine, thio urea, EDTA, humic substances, bile compounds) on the octanol solubility of the PGM. The results demonstrated a significant influence of all agents used. L-Methionine and thio urea decreased the lipid solubility. In contrast, the presence of EDTA, humic substances and especially bile caused a higher transfer of metals in the octanol phase. For most complexing agents tested, the transfer of Pd to the lipid phase was significantly higher compared with Rh and Pt, except for bile acid where the highest octanol solubility was found for Pt. Recent experimental results on PGM accumulation in zebra mussels confirm a high bioaccumulation of Pd which could be predicted from the lipid solubility.

1.7 nm Platinum Nanoparticles: Synthesis with Glucose Starch, Characterization and Catalysis

DEFF Research Database (Denmark)

Engelbrekt, Christian; Sørensen, Karsten Holm; Lubcke, T.

2010-01-01

Monodisperse platinum nanoparticles (PtNPs) were synthesized by a green recipe. Glucose serves as a reducing agent and starch as a stabilization agent to protect the freshly formed PtNP cores in buffered aqueous solutions. Among the ten buffers studied, 2-(N-morpholino)ethanesulfonic acid (MES), ...

The chemotherapeutic agent paclitaxel selectively impairs reversal learning while sparing prior learning, new learning and episodic memory.

Science.gov (United States)

Panoz-Brown, Danielle; Carey, Lawrence M; Smith, Alexandra E; Gentry, Meredith; Sluka, Christina M; Corbin, Hannah E; Wu, Jie-En; Hohmann, Andrea G; Crystal, Jonathon D

2017-10-01

Chemotherapy is widely used to treat patients with systemic cancer. The efficacy of cancer therapies is frequently undermined by adverse side effects that have a negative impact on the quality of life of cancer survivors. Cancer patients who receive chemotherapy often experience chemotherapy-induced cognitive impairment across a variety of domains including memory, learning, and attention. In the current study, the impact of paclitaxel, a taxane derived chemotherapeutic agent, on episodic memory, prior learning, new learning, and reversal learning were evaluated in rats. Neurogenesis was quantified post-treatment in the dentate gyrus of the same rats using immunostaining for 5-Bromo-2'-deoxyuridine (BrdU) and Ki67. Paclitaxel treatment selectively impaired reversal learning while sparing episodic memory, prior learning, and new learning. Furthermore, paclitaxel-treated rats showed decreases in markers of hippocampal cell proliferation, as measured by markers of cell proliferation assessed using immunostaining for Ki67 and BrdU. This work highlights the importance of using multiple measures of learning and memory to identify the pattern of impaired and spared aspects of chemotherapy-induced cognitive impairment. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of tegafur-uracil in advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy.

Science.gov (United States)

Maolake, Aerken; Izumi, Kouji; Takahashi, Rie; Itai, Shingo; Machioka, Kazuaki; Yaegashi, Hiroshi; Nohara, Takahiro; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Namiki, Mikio

2015-03-01

Platinum-based chemotherapy is the first-line treatment for advanced urinary tract urothelial cancers. However, the optimal second-line treatment is unclear. Although tegafur-uracil is sometimes used for advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy, there is little evidence regarding its use as a second-line treatment. Advanced urothelial cancer patients previously treated with platinum-based chemotherapy were retrospectively analyzed. Overall survival (OS) was compared between patients with and without tegafur-uracil treatment. Thirty-one patients (27 and 4 patients with and without tegafur-uracil treatment, respectively) were analyzed. OS from the last day of the final chemotherapy course was better in patients with tegafur-uracil treatment than in those without (p<0.001, 358 and 66.5 days of the median survival time, respectively). Tegafur-uracil may be a candidate for the secondary treatment of advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Effect of dicycloplatin, a novel platinum chemotherapeutical drug, on inhibiting cell growth and inducing cell apoptosis.

Directory of Open Access Journals (Sweden)

Guang-quan Li

Full Text Available Dicycloplatin, a new supramolecular platinum-based antitumor drug, has been approved by the State Food and Administration (SFDA of China. In this study, we investigated the anticancer activity of dicycloplatin in cancer cells and signaling pathways involved in dicycloplatin-induced apoptosis. Dicycloplatin inhibited the proliferation of cancer cells and increased the percentage of apoptosis in a concentration-dependent manner. Besides, some apoptosis related events were observed after treatment with dicycloplatin, including increase of reactive oxygen species (ROS, collapse of mitochondrial membrane potential (Δψm, release of cytochrome c from the mitochondria to the cytosol, upregulation of p53, which were accompanied by activation of caspase-9, caspase-3, caspase-8, and poly (ADP-ribose polymerase cleavage in a concentration-dependent manner. The role of apoptosis in dicycloplatin-mediated cell death was further confirmed by the concomitant treatment with caspase-8 or caspase-9 inhibitors, which inhibited apoptosis and PARP cleavage. Intracellular glutathione (GSH was also found to inhibit the cytotoxic effect of dicycloplatin. In conclusion, these findings suggest that dicycloplatin induces apoptosis through ROS stress-mediated death receptor pathway and mitochondrial pathway which is similar to carboplatin.

Association of well-characterized lung cancer lncRNA polymorphisms with lung cancer susceptibility and platinum-based chemotherapy response.

Science.gov (United States)

Gong, Wei-Jing; Yin, Ji-Ye; Li, Xiang-Ping; Fang, Chao; Xiao, Di; Zhang, Wei; Zhou, Hong-Hao; Li, Xi; Liu, Zhao-Qian

2016-06-01

Long non-coding RNAs (lncRNAs) play important roles in carcinogenesis and drug efficacy. Platinum-based chemotherapy is first-line treatment for lung cancer chemotherapy. In this study, we aimed to investigate the association of well-characterized lung cancer lncRNA genetic polymorphisms with the lung cancer susceptibility and platinum-based chemotherapy response. A total of 498 lung cancer patients and 213 healthy controls were recruited in the study. Among them, 467 patients received at least two cycles of platinum-based chemotherapy. Thirteen polymorphisms in HOXA distal transcript antisense RNA (HOTTIP), HOX transcript antisense intergenic RNA (HOTAIR), H19, CDKN2B antisense RNA 1 (ANRIL), colon cancer-associated transcript 2 (CCAT2), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and maternally expressed gene 3 (MEG3) genes were genotyped by allele-specific MALDI-TOF mass spectrometry. We found that patients with HOTTIP rs5883064 C allele or rs1859168 A allele had increased lung cancer risk (P = 0.01, P = 0.01, respectively). CCAT2 rs6983267 (P = 0.02, adenocarcinoma) and H19 rs2107425 (P = 0.02, age under 50 years) showed strong relationship with lung cancer susceptibility. CCAT2 rs6983267, H19 rs2839698, MALAT1 rs619586, and HOTAIR rs7958904 were associated with platinum-based chemotherapy response in dominant model ((P = 0.02, P = 0.04, P = 0.04, P = 0.01, respectively). ANRIL rs10120688 (P = 0.02, adenocarcinoma) and rs1333049 (P = 0.04, small-cell lung cancer), H19 rs2107425 (P = 0.02, small-cell lung cancer) and HOTAIR rs1899663 (P = 0.03, male; P = 0.03, smoker) were associated with response to platinum-based chemotherapy. HOTTIP, CCAT2, H19, HOTAIR, MALATI, ANRIL genetic polymorphisms were significantly associated with lung cancer susceptibility or platinum-based chemotherapy response. They may be potential clinical biomarkers to predict lung cancer risk and platinum-based

The synthesis of potential chemotherapeutic agents based on leads from nature

International Nuclear Information System (INIS)

Brimble, M.A.

2001-01-01

Our research group has developed an efficient synthesis of several simpler members of pyranonaphthoquinone antibiotics using a novel annulation of a 2-acetylnaphthoquinone using 2- trimethylsilyloxyfuran to afford a furonaphthofuran ring system that then underwent oxidative rearrangement to the desired pyranonaphthoquinone ring system. This methodology was then successfully applied to the synthesis of the spiroacetal-containing pyranonaphthoquinone, griseusin A, and the C-glycosidic pyranonaphthoquinone, medermycin, which is effective against neoplastic cells in vitro, antibiotic resistant cell lines of L5178Y lymphoblastoma, and inhibits human leukaemia K 562 cells as well as platelet aggregation. The first efficient synthesis of a dimeric pyranonaphthoquinone as present in the antiviral agent, crisamycin A and γ-actinorhodin, has also been successfully effected using an efficient double furofuran-oxidative rearrangement strategy starting from a bis(2-acetyl-1,4-naphthoquinone)

Platinum-group elements and gold in base metal sulfides, platinum-group minerals, and Re-Os isotope compositions of the Uitkomst complex, South Africa

Czech Academy of Sciences Publication Activity Database

Trubač, Jakub; Ackerman, Lukáš; Gauert, Ch.; Ďurišová, Jana; Hrstka, Tomáš

2018-01-01

Roč. 113, č. 2 (2018), s. 439-461 ISSN 0361-0128 R&D Projects: GA ČR GA13-15390S Institutional support: RVO:67985831 Keywords : binary alloys * copper compounds * economic geology * gold * iridium * isotopes * ore deposits * osmium * palladium * platinum * platinum metals * pyrites * Rhenium * rhenium alloys * ruthenium * solid solutions * sulfur compounds * crustal materials * mass-balance calculations * massive sulfides * mineralized zone * monosulfide solid solutions * platinum group elements * platinum group elements (PGEs) * platinum group minerals Subject RIV: DB - Geology ; Mineralogy; AC - Archeology, Anthropology, Ethnology (ARUB-Q) OBOR OECD: Geology; Archaeology (ARUB-Q) Impact factor: 2.519, year: 2016

Electrochemical behaviour of platinum in hydrogen peroxide solution (1963)

International Nuclear Information System (INIS)

Prost, G.H.

1963-06-01

The relative stability of hydrogen peroxide in aqueous solution at 25 deg. C, allows its amperometric determination from the theory, using either its cathodic reduction or its anodic oxidation. The cathodic reduction yields a wave on a platinum electrode only when some oxygen is present in the solution. It cannot, therefore, be used for electrochemical determination. On the other hand, the anodic oxidation on platinum produces a wave which might be used. However, a passivation of platinum occurs at the same time. This passivation process is studied by means of potentio-kinetic, potentio-static, intensio-static curves and of pH measurements in the vicinity of the anode. A mechanism for passivation is presented, which takes into account the role of hydrogen peroxide as a reducing agent. This passivation rules out any analytical application of the oxidation reaction of hydrogen peroxide. (author) [fr

Studies on uptake and distribution of chemotherapeutic agents to malignant tumors of the head and neck in rabbits, 2. /sup 3/H-Adriamycin

Energy Technology Data Exchange (ETDEWEB)

Yamada, R. (Gifu Univ. (Japan). Faculty of Medicine)

1981-09-01

Experiments were performed to investigate incorporation and distribution of chemotherapeutic agents into malignant tumors of the head and neck by microautoradiographic and electron microscopic-autoradiographic observations of VX2 carcinoma transplanted in the lower genial region of rabbits after injection of /sup 3/H-Adriamycin as a tracer. The following findings were obtained. 1. On microautoradiograms, /sup 3/H-Adriamycin was distributed predominantly in the nucleoplasm, rather than in the cytoplasm, of tumor tissues. 2. At the ultrastructural level, /sup 3/H-Adriamycin was localized in the nuclear membrane and nucleoli within the nucleoplasm and in the rough endoplasmic reticulum and secretory granules within the cytoplasm. 3. These findings seem to indicate that Adriamycin may inhibit the synthesis of DNA and RNA in the nucleoplasm.

Strategies for the fabrication of porous platinum electrodes

Energy Technology Data Exchange (ETDEWEB)

Kloke, Arne; Stetten, Felix von; Kerzenmacher, Sven [Laboratory for MEMS Applications, Department of Microsystems Engineering-IMTEK, University of Freiburg, Freiburg (Germany); Zengerle, Roland [Laboratory for MEMS Applications, Department of Microsystems Engineering-IMTEK, University of Freiburg, Freiburg (Germany); BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universitaet Freiburg (Germany)

2011-11-16

Porous platinum is of high technological importance due to its various applications in fuel cells, sensors, stimulation electrodes, mechanical actuators and catalysis in general. Based on a discussion of the general principles behind the reduction of platinum salts and corresponding deposition processes this article discusses techniques available for platinum electrode fabrication. The numerous, different strategies available to fabricate platinum electrodes are reviewed and discussed in the context of their tuning parameters, strengths and weaknesses. These strategies comprise bottom-up approaches as well as top-down approaches. In bottom-up approaches nanoparticles are synthesized in a first step by chemical, photochemical or sonochemical means followed by an electrode formation step by e.g. thin film technology or network formation to create a contiguous and conducting solid electrode structure. In top-down approaches fabrication starts with an already conductive electrode substrate. Corresponding strategies enable the fabrication of substrate-based electrodes by e.g. electrodeposition or the fabrication of self-supporting electrodes by dealloying. As a further top-down strategy, this review describes methods to decorate porous metals other than platinum with a surface layer of platinum. This way, fabrication methods not performable with platinum can be applied to the fabrication of platinum electrodes with the special benefit of low platinum consumption. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

Science.gov (United States)

O'Malley, David M; Vetter, Monica Hagan; Cohn, David E; Khan, Ambar; Hays, John L

2017-06-01

Platinum-based chemotherapies are a standard treatment for both initial and recurrent gynecologic cancers. Given this widespread use, it is important to be aware of the features of platinum hypersensitivity reactions and the subsequent treatment of these reactions. There is also increasing interest in the development of desensitization protocols to allow patients with a history of platinum hypersensitivity to receive further platinum based therapy. In this review, we describe the management of platinum hypersensitivity reactions and the desensitization protocols utilized at our institution. We also describe the clinical categorizations utilized to triage patients to appropriate desensitization protocols. Copyright © 2017 Elsevier Inc. All rights reserved.

Platinum-based chemotherapy with or without thoracic radiation therapy in patients with unresectable thymic carcinoma

International Nuclear Information System (INIS)

Nakamura, Yoichi; Kunitoh, Hideo; Kubota, Kaoru

2000-01-01

Thymic carcinoma is a rare mediastinal neoplasm with poor prognosis. Although the clinical benefit of chemotherapy for thymic carcinoma is controversial, cisplatin-based chemotherapy with or without radiation therapy is ordinarily adopted in advanced cases. We evaluated the clinical outcome of platinum-based chemotherapy with or without radiation therapy in unresectable thymic carcinoma patients. Ten patients with unresectable thymic carcinoma were treated with platinum-based chemotherapy with or without radiation therapy in the National Cancer Center Hospital between 1989 and 1998. We reviewed the histological type, treatment, response and survival of these patients. Four of the 10 patients responded to chemotherapy and both the median progression-free survival period and the median response duration were 6.0 months. The median survival time was 11.0 months. There was no relationship between histological classification and prognosis. Platinum-based chemotherapy with or without thoracic radiation is, regardless of tumor histology, marginally effective in advanced thymic carcinoma patients, giving only a modest tumor response rate and short response duration and survival. (author)

Cytotoxic effects of chemotherapeutic drugs and heterocyclic compounds at application on the cells of primary culture of neuroepithelium tumors.

Science.gov (United States)

Kulchitsky, Vladimir A; Potkin, Vladimir I; Zubenko, Yuri S; Chernov, Alexander N; Talabaev, Michael V; Demidchik, Yuri E; Petkevich, Sergei K; Kazbanov, Vladimir V; Gurinovich, Tatiana A; Roeva, Margarita O; Grigoriev, Dmitry G; Kletskov, Alexei V; Kalunov, Vladimir N

2012-01-01

Neuroepithelial tumor cells were cultured in vitro. The biopsy material was taken from 93 children at removal of the brain tumors during neurosurgical operations. The individual features of the cells sensitivity of primary cultures in respect to protocol-approved chemotherapy drugs and changes in the Interleukin-6 (Il-6) level in the culture medium after the application of chemotherapy were established. The initial level of Il-6 exceeded 600.0 pg/ml in the cultural medium with histologically verified pilomyxoid astrocytoma cells, and ranged from 100.0 to 200.0 pg/ml in the medium at cultivation of ganglioneuroblastoma and pilocytic astrocytoma. A decrease in the Il-6 level in the medium culture of primary tumors cells was observed after the application of chemotherapeutic agents on the cells of pilomyxoid astrocytoma, astrocytomas, and pilocytic desmoplastic/nodular medulloblastoma. The production of Il-6 increased after application of cytostatic drugs on the cells of oligoastrocytomas. A decrease in Il-6 level after application of Cisplatin and Methotrexate and a 5-10 fold increase in the level of Il-6 after application of Etoposide, Carboplatin, Cytarabine, and Gemcitabine were registered in the medium with ganglioneuroblastoma. To improve the cytotoxic action of chemotherapeutic agents, the combined application of cytostatics with heterocyclic compounds was carried out. A computer modeling of ligand-protein complexes of carbamide using the Dock 6.4 and USF Chimera program packages was performed with molecular mechanics method. Special attention was drawn to the ability of several isoxazole heterocycles and isothiazolyl to inhibit the tyrosine kinase. It was proved in vitro that the joint application of chemotherapeutic agents and heterocyclic compounds could reduce the concentration of the cytostatic factor by 10 or more times, having maintained the maximum cytotoxic effect. It was assumed that the target amplification of cytotoxic action of chemotherapeutic

Validation and use of microdialysis for determination of pharmacokinetic properties of the chemotherapeutic agent mitomycin C - an experimental study

International Nuclear Information System (INIS)

Sørensen, Olaf; Andersen, Anders; Olsen, Harald; Alexandr, Kristian; Ekstrøm, Per Olaf; Giercksky, Karl-Erik; Flatmark, Kjersti

2010-01-01

Mitomycin C is a chemotherapeutic agent used in the treatment of peritoneal surface malignancies, administered as hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. Pharmacokinetic studies have been based on analyses of blood, urine and abdominal perfusate, but actual tissue concentrations of the drug have never been determined. Microdialysis is an established method for continuous monitoring of low-molecular substances in tissues, and in the present study microdialysis of mitomycin C was studied in vitro and in vivo. Using in vitro microdialysis, relative recovery was determined when varying drug concentration, temperature and perfusion flow rate. In vivo microdialysis was performed in rats to verify long-term stability of relative recovery in four compartments (vein, peritoneum, extraperitoneal space and hind leg muscle). Subsequently, intravenous and intraperitoneal bolus infusion experiments were performed and pharmacokinetic parameters were calculated. In vitro, compatibility of mitomycin C and microdialysis equipment was demonstrated, and relative recovery was stable over an adequate concentration range, moderately increased by raising medium temperature and increased when flow rate was reduced, all according to theory. In vivo, stable relative recovery was observed over seven hours. Mitomycin C exhibited fast and even distribution in rat tissues, and equal bioavailability was achieved by intravenous and intraperitoneal infusion. The half-life of mitomycin C calculated after intravenous infusion was 40 minutes. Mitomycin C concentration can be reliable monitored in vivo using microdialysis, suggesting that this technique can be used in pharmacokinetic studies of this drug during hyperthermic intraperitoneal chemotherapy

Utilization of a selective tumour artery catheterization technique for the intra-arterial delivery of chemotherapeutic agents and radiopharmaceuticals in a combined chemotherapy-radiotherapy clinical research programme

International Nuclear Information System (INIS)

Wiley, A.L. Jr.; Wirtanen, G.W.; Holden, J.E.; Polcyn, R.E.

1977-01-01

Combined intra-arterial chemotherapeutic agents (principally actinomycin-D) and radiation therapy has been utilized in the treatment of 35 patients with massive unresectable malignancies. The goals may be separated into three distinct categories. An attempt has been made to convert unresectable malignancies to surgical resectability, to provide a definitive therapy for massive tumours in patients who either refuse surgery or are not surgery candidates, and to provide palliation. Twelve of 15 initially unresectable tumours treated with actinomycin-D became surgically resectable (no resection was attempted in the other four because they either developed metastasis during therapy or did not complete the therapy), 4 of 6 massive tumours treated definitively have remained locally controlled from 18 to 108 months, and 7 of 9 patients treated palliatively were significantly benefited by the therapy. Impressive responses were also achieved in several patients treated with intra-arterial 5-fluorouracil and 5-iodo-2'-deoxyuridine. The authors therefore consider combined, concurrent radiation therapy and intra-arterially administered chemotherapeutic agents worthy of further clinical investigation as a means of treating massive malignancies. They also suggest that the best chance of optimizing the therapeutic ratio of such therapy is dependent primarily on a proper understanding of clinical tumour vascularity and of its subsequent effect on drug and oxygen distributions within the radiation treatment volume. Accordingly, tumour vascularity has been clinically evaluated by the use of intra-arterially administered radiopharmaceuticals. Such clinical data, in conjunction with radiobiological data, might in the future be utilized to optimize both low and high LET combined therapy by allowing for correction of the physical isodose for drug and oxygen concentration variations. (author)

A novel reusable platinum nanocatalyst

International Nuclear Information System (INIS)

Zhou Weiqiang; Wang Jing; Wang Chuanyi; Du Yukou; Xu Jingkun; Yang Ping

2010-01-01

Recyclability of noble metal catalysts is a challenging issue when dealing with their industrial applications. Smart pH-sensitive Pt nanoparticles were successfully prepared for the first time by using octa(N,N-diacetic acid phenylamine)silsesquioxane (OAPAS) as a macromolecular protective agent. As-prepared Pt nanoparticles can self-aggregate or redisperse by only changing the pH of the system solution. In the weak acidic or alkaline solution (pH > 4.0), the Pt nanoparticles dispersed homogenously; while in the acidic solution (pH = 2.5), they self-aggregated. The dynamic self-aggregation and redispersion processes of the Pt nanoparticles driven by pH changes were revealed by transmission electron microscopy measurements. Electrocatalytic experiments proved that the platinum nanoparticles as a recyclable catalyst showed excellent activity for the hydrogenation of aldehyde after runs of five times. Such platinum nanoparticles are thereby anticipated to have great potential functioning as 'smart' catalysts for industrial applications.

Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium

International Nuclear Information System (INIS)

Konno, T.

1990-01-01

Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors

Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin

International Nuclear Information System (INIS)

DeSilva, M.A.; Wepsic, H.T.; Mizushima, Y.; Nikcevich, D.A.; Larson, C.H.

1985-01-01

The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin

Persistence of DNA adducts, hypermutation and acquisition of cellular resistance to alkylating agents in glioblastoma.

Science.gov (United States)

Head, R J; Fay, M F; Cosgrove, L; Y C Fung, K; Rundle-Thiele, D; Martin, J H

2017-12-02

Glioblastoma is a lethal form of brain tumour usually treated by surgical resection followed by radiotherapy and an alkylating chemotherapeutic agent. Key to the success of this multimodal approach is maintaining apoptotic sensitivity of tumour cells to the alkylating agent. This initial treatment likely establishes conditions contributing to development of drug resistance as alkylating agents form the O 6 -methylguanine adduct. This activates the mismatch repair (MMR) process inducing apoptosis and mutagenesis. This review describes key juxtaposed drivers in the balance between alkylation induced mutagenesis and apoptosis. Mutations in MMR genes are the probable drivers for alkylation based drug resistance. Critical to this interaction are the dose-response and temporal interactions between adduct formation and MMR mutations. The precision in dose interval, dose-responses and temporal relationships dictate a role for alkylating agents in either promoting experimental tumour formation or inducing tumour cell death with chemotherapy. Importantly, this resultant loss of chemotherapeutic selective pressure provides opportunity to explore novel therapeutics and appropriate combinations to minimise alkylation based drug resistance and tumour relapse.

Radiation Chemistry Studies on Chemotherapeutic Agents

DEFF Research Database (Denmark)

Gohn, M.; Getoff, N.; Bjergbakke, Erling

1977-01-01

Adrenalin has been studied as a model radiation protective agent by means of pulse radiolysis in aqueous solutions. The rate constants for the reactions of adrenalin with e–aq and OH were determined : k(e–aq+ adr—NH+2)= 7.5 × 108 dm3 mol–1 s–1, k(e–aq+ adr—NH)= 2.5 × 108 dm3 mol–1 s–1, and k......(OH + adr)= 2.2 × 1010 dm3 mol–1 s–1(pH = 9.2). e–aq attacks the amino group by splitting off methylamine, whereas OH and O–aq lead to the formation of the corresponding adducts of the cyclohexadienyl type. OH radicals can also abstract an electron from an O– group at pH > 8....

Adenosine triphosphate-based chemotherapy response assay (ATP-CRA)-guided platinum-based 2-drug chemotherapy for unresectable nonsmall-cell lung cancer.

Science.gov (United States)

Moon, Yong Wha; Choi, Sung Ho; Kim, Yong Tai; Sohn, Joo Hyuk; Chang, Joon; Kim, Se Kyu; Park, Moo Suk; Chung, Kyung Young; Lee, Hyoun Ju; Kim, Joo-Hang

2007-05-01

The study investigated correlations between adenosine triphosphate / chemotherapy response assay (ATP-CRA) and clinical outcomes after ATP-CRA-guided platinum-based chemotherapy for unresectable nonsmall-cell lung cancer (NSCLC). The authors performed an in vitro chemosensitivity test, ATP-CRA, to evaluate the chemosensitivities of anticancer drugs such as cisplatin, carboplatin, paclitaxel, docetaxel, gemcitabine, and vinorelbine for chemonaive, unresectable NSCLC. The cell death rate was determined by measuring the intracellular ATP levels of drug-exposed cells compared with untreated controls. A sensitive drug was defined as a drug producing 30% or more reduction in ATP compared with untreated controls. Assay-guided platinum-based 2-drug chemotherapy was given to patients with pathologically confirmed NSCLC. Thirty-four patients were enrolled. Thirty tumor specimens were obtained by bronchoscopic biopsies and 4 obtained surgically. The median age was 61 years and 27 patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. The response rate was 43.8%. At a median follow-up period of 16.9 months, the median progression-free and overall survivals were 3.6 and 11.2 months, respectively. Patients were dichotomized into the platinum-sensitive (S; 20 patients) and resistant (R; 14 patients) groups. The positive/negative predictive values were 61.1% and 78.6% with a predictive accuracy of 68.8%. Although without significant differences in pretreatment parameters, the S-group showed better clinical response (P=.036), longer progression-free survival (P=.060), and longer overall survival (P=.025). Despite using bronchoscopic biopsied specimens, ATP-CRA and clinical outcomes correlated well after assay-guided platinum-based 2-drug chemotherapy for unresectable NSCLC. There was a favorable response and survival in the platinum-sensitive vs resistant groups. Copyright (c) 2007 American Cancer Society

Development of a novel, physiologically relevant cytotoxicity model: Application to the study of chemotherapeutic damage to mesenchymal stromal cells

International Nuclear Information System (INIS)

May, Jennifer E.; Morse, H. Ruth; Xu, Jinsheng; Donaldson, Craig

2012-01-01

There is an increasing need for development of physiologically relevant in-vitro models for testing toxicity, however determining toxic effects of agents which undergo extensive hepatic metabolism can be particularly challenging. If a source of such metabolic enzymes is inadequate within a model system, toxicity from prodrugs may be grossly underestimated. Conversely, the vast majority of agents are detoxified by the liver, consequently toxicity from such agents may be overestimated. In this study we describe the development of a novel in-vitro model, which could be adapted for any toxicology setting. The model utilises HepG2 liver spheroids as a source of metabolic enzymes, which have been shown to more closely resemble human liver than traditional monolayer cultures. A co-culture model has been developed enabling the effect of any metabolised agent on another cell type to be assessed. This has been optimised to enable the study of damaging effects of chemotherapy on mesenchymal stem cells (MSC), the supportive stem cells of the bone marrow. Several optimisation steps were undertaken, including determining optimal culture conditions, confirmation of hepatic P450 enzyme activity and ensuring physiologically relevant doses of chemotherapeutic agents were appropriate for use within the model. The developed model was subsequently validated using several chemotherapeutic agents, both prodrugs and active drugs, with resulting MSC damage closely resembling effects seen in patients following chemotherapy. Minimal modifications would enable this novel co-culture model to be utilised as a general toxicity model, contributing to the drive to reduce animal safety testing and enabling physiologically relevant in-vitro study. -- Highlights: ► An in vitro model was developed for study of drugs requiring hepatic metabolism ► HepG2 spheroids were utilised as a physiologically relevant source of liver enzymes ► The model was optimised to enable study of chemotherapeutic

Development of a novel, physiologically relevant cytotoxicity model: Application to the study of chemotherapeutic damage to mesenchymal stromal cells

Energy Technology Data Exchange (ETDEWEB)

May, Jennifer E., E-mail: Jennifer2.May@uwe.ac.uk; Morse, H. Ruth, E-mail: Ruth.Morse@uwe.ac.uk; Xu, Jinsheng, E-mail: Jinsheng.Xu@uwe.ac.uk; Donaldson, Craig, E-mail: Craig.Donaldson@uwe.ac.uk

2012-09-15

There is an increasing need for development of physiologically relevant in-vitro models for testing toxicity, however determining toxic effects of agents which undergo extensive hepatic metabolism can be particularly challenging. If a source of such metabolic enzymes is inadequate within a model system, toxicity from prodrugs may be grossly underestimated. Conversely, the vast majority of agents are detoxified by the liver, consequently toxicity from such agents may be overestimated. In this study we describe the development of a novel in-vitro model, which could be adapted for any toxicology setting. The model utilises HepG2 liver spheroids as a source of metabolic enzymes, which have been shown to more closely resemble human liver than traditional monolayer cultures. A co-culture model has been developed enabling the effect of any metabolised agent on another cell type to be assessed. This has been optimised to enable the study of damaging effects of chemotherapy on mesenchymal stem cells (MSC), the supportive stem cells of the bone marrow. Several optimisation steps were undertaken, including determining optimal culture conditions, confirmation of hepatic P450 enzyme activity and ensuring physiologically relevant doses of chemotherapeutic agents were appropriate for use within the model. The developed model was subsequently validated using several chemotherapeutic agents, both prodrugs and active drugs, with resulting MSC damage closely resembling effects seen in patients following chemotherapy. Minimal modifications would enable this novel co-culture model to be utilised as a general toxicity model, contributing to the drive to reduce animal safety testing and enabling physiologically relevant in-vitro study. -- Highlights: ► An in vitro model was developed for study of drugs requiring hepatic metabolism ► HepG2 spheroids were utilised as a physiologically relevant source of liver enzymes ► The model was optimised to enable study of chemotherapeutic

Solvent extraction of platinum with thiobenzanilide. Separation of platinum from copper

International Nuclear Information System (INIS)

Shkil', A.N.; Zolotov, Yu.A.

1989-01-01

The solvent extraction of micro concentrations of platinum has been investigated from hydrochloric acid media using thiobenzanilide in the presence of SnCl 2 and KI. In the presence of SnCl 2 platinum is extracted rapidly and to significant completion. Conditions have been developed for the quantitative extraction of platinum. The authors have also examined the solvent extraction of copper(II) using thiobenzanilide, interference due to copper(II) and iron(III) on solvent extraction of platinum, and methods to suppress this interference. A procedure has also been developed for the separation of platinum from copper. Solvent extraction of metals was studied using radioactive isotopes: 197 Pt, 64 Cu, 59 Fe, 198 Au, 109 Pd, 110m Ag

FANCD2 re-expression is associated with glioma grade and chemical inhibition of the Fanconi Anaemia pathway sensitises gliomas to chemotherapeutic agents

Science.gov (United States)

Patil, Abhijit A.; Sayal, Parag; Depondt, Marie-Lise; Beveridge, Ryan D.; Roylance, Anthony; Kriplani, Deepti H.; Myers, Katie N.; Cox, Angela; Jellinek, David; Fernando, Malee; Carroll, Thomas A.; Collis, Spencer J.

2014-01-01

Brain tumours kill more children and adults under 40 than any other cancer. Around half of primary brain tumours are glioblastoma multiforme (GBMs) where treatment remains a significant challenge. GBM survival rates have improved little over the last 40 years, thus highlighting an unmet need for the identification/development of novel therapeutic targets and agents to improve GBM treatment. Using archived and fresh glioma tissue, we show that in contrast to normal brain or benign schwannomas GBMs exhibit re-expression of FANCD2, a key protein of the Fanconi Anaemia (FA) DNA repair pathway, and possess an active FA pathway. Importantly, FANCD2 expression levels are strongly associated with tumour grade, revealing a potential exploitable therapeutic window to allow inhibition of the FA pathway in tumour cells, whilst sparing normal brain tissue. Using several small molecule inhibitors of the FA pathway in combination with isogenic FA-proficient/deficient glioma cell lines as well as primary GBM cultures, we demonstrate that inhibition of the FA pathway sensitises gliomas to the chemotherapeutic agents Temozolomide and Carmustine. Our findings therefore provide a strong rationale for the development of novel and potent inhibitors of the FA pathway to improve the treatment of GBMs, which may ultimately impact on patient outcome. PMID:25071006

Radiation chemistry studies on chemotherapeutic agents

International Nuclear Information System (INIS)

Gohn, M.; Getoff, N.; Bjergbakke, E.

1977-01-01

Adrenalin has been studied as a model radiation protective agent by means of pulse radiolysis in aqueous solutions. The rate constants for the reactions of adrenalin with e - sub(aq) and OH were determined: k(e - sub(aq) + adr -NH + 2 ) = 7.5 x 10 8 dm 3 mol -1 s -1 , k(e - sub(aq) + adr - NH) = 2.5 x 10 8 dm 3 mol -1 s -1 , and k(OH + adr) = 2.2 x 10 -10 dm 3 mol -1 s -1 (pH = 9.2). e - sub(aq) attacks the amino group by splitting off methylamine, whereas OH and O - sub(aq) lead to the formation of the corresponding adducts of the cyclohexadienyl type. OH radicals can also abstract an electron from an 0 - group at pH > 8. (author)

The development of platinum-based alloys and their thermodynamic database

OpenAIRE

Cornish L.A.; Hohls J.; Hill P.J.; Prins S.; Süss R.; Compton D.N.

2002-01-01

A series of quaternary platinum-based alloys have been demonstrated to exhibit the same two-phase structure as Ni-based superalloys and showed good mechanical properties. The properties of ternary alloys were a good indication that the quaternary alloys, with their better microstructure, will be even better. The quaternary alloy composition has been optimised at Pt84:Al11:Ru2:Cr3 for the best microstructure and hardness. Work has begun on establishing a thermodynamic database for Pt-Al-Ru-Cr ...

Human toxoplasmosis-Searching for novel chemotherapeutics.

Science.gov (United States)

Antczak, Magdalena; Dzitko, Katarzyna; Długońska, Henryka

2016-08-01

The protozoan Toxoplasma gondii, an obligate intracellular parasite, is an etiological agent of human and animal toxoplasmosis. Treatment regimens for T. gondii-infected patients have not essentially changed for years. The most common chemotherapeutics used in the therapy of symptomatic toxoplasmosis are a combination of pyrimethamine and sulfadiazine plus folinic acid or a combination of pyrimethamine with lincosamide or macrolide antibiotics. To protect a fetus from parasite transplacental transmission, therapy of pregnant women is usually based on spiramycin, which is quite safe for the organism, but not efficient in the treatment of infected children. Application of recommended drugs limits replication of T. gondii, however, it may be associated with numerous an severe adverse effects. Moreover, medicines have no impact on the tissue cysts of the parasite located predominantly in a brain and muscles. Thus, there is urgent need to develop new drugs and establish "gold standard" treatment. In this review classical treatment of toxoplasmosis as well as potential compounds active against T. gondii have been discussed. For two last decades studies on the development of new anti-T. gondii medications have been focused on both natural and novel synthetic compounds based on existing chemical scaffolds. They have revealed several promising drug candidates characterized by a high selectivity, the low IC50 (the half maximal inhibitory concentration) and low cytotoxicity towards host cells. These drugs are expected to replace or supplement current anti-T. gondii drug arsenal soon. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Meta-Analysis on Pharmacogenetics of Platinum-Based Chemotherapy in Non Small Cell Lung Cancer (NSCLC) Patients

Science.gov (United States)

Yin, Ji-Ye; Huang, Qiong; Zhao, Ying-Chun; Zhou, Hong-Hao; Liu, Zhao-Qian

2012-01-01

Aim To determine the pharmacogenetics of platinum-based chemotherapy in Non Small Cell Lung Cancer (NSCLC) patients. Methods Publications were selected from PubMed, Cochrane Library and ISI Web of Knowledge. A meta-analysis was conducted to determine the association between genetic polymorphisms and platinum-based chemotherapy by checking odds ratio (OR) and 95% confidence interval (CI). Results Data were extracted from 24 publications, which included 11 polymorphisms in 8 genes for meta-analysis. MDR1 C3435T (OR = 1.97, 95% CI: 1.11–3.50, P = 0.02), G2677A/T (OR = 2.61, 95% CI: 1.44–4.74, P = 0.002) and GSTP1 A313G (OR = 0.32, 95% CI: 0.17–0.58, P = 0.0002) were significantly correlated with platinum-based chemotherapy in Asian NSCLC patients. Conclusion Attention should be paid to MDR1 C3435T, G2677A/T and GSTP1 A313G for personalized chemotherapy treatment for NSCLC patients in Asian population in the future. PMID:22761669

Electrochemical DNA biosensors based on platinum nanoparticles combined carbon nanotubes

International Nuclear Information System (INIS)

Zhu Ningning; Chang Zhu; He Pingang; Fang Yuzhi

2005-01-01

Platinum nanoparticles were used in combination with multi-walled carbon nanotubes (MWCNTs) for fabricating sensitivity-enhanced electrochemical DNA biosensor. Multi-walled carbon nanotubes and platinum nanoparticles were dispersed in Nafion, which were used to fabricate the modification of the glassy carbon electrode (GCE) surface. Oligonucleotides with amino groups at the 5' end were covalently linked onto carboxylic groups of MWCNTs on the electrode. The hybridization events were monitored by differential pulse voltammetry (DPV) measurement of the intercalated daunomycin. Due to the ability of carbon nanotubes to promote electron-transfer reactions, the high catalytic activities of platinum nanoparticles for chemical reactions, the sensitivity of presented electrochemical DNA biosensors was remarkably improved. The detection limit of the method for target DNA was 1.0 x 10 -11 mol l -1

Platinum-group elements

Science.gov (United States)

Zientek, Michael L.; Loferski, Patricia J.; Parks, Heather L.; Schulte, Ruth F.; Seal, Robert R.; Schulz, Klaus J.; DeYoung,, John H.; Seal, Robert R.; Bradley, Dwight C.

2017-12-19

The platinum-group elements (PGEs)—platinum, palladium, rhodium, ruthenium, iridium, and osmium—are metals that have similar physical and chemical properties and tend to occur together in nature. PGEs are indispensable to many industrial applications but are mined in only a few places. The availability and accessibility of PGEs could be disrupted by economic, environmental, political, and social events. The United States net import reliance as a percentage of apparent consumption is about 90 percent.PGEs have many industrial applications. They are used in catalytic converters to reduce carbon monoxide, hydrocarbon, and nitrous oxide emissions in automobile exhaust. The chemical industry requires platinum or platinum-rhodium alloys to manufacture nitric oxide, which is the raw material used to manufacture explosives, fertilizers, and nitric acid. In the petrochemical industry, platinum-supported catalysts are needed to refine crude oil and to produce aromatic compounds and high-octane gasoline. Alloys of PGEs are exceptionally hard and durable, making them the best known coating for industrial crucibles used in the manufacture of chemicals and synthetic materials. PGEs are used by the glass manufacturing industry in the production of fiberglass and flat-panel and liquid crystal displays. In the electronics industry, PGEs are used in computer hard disks, hybridized integrated circuits, and multilayer ceramic capacitors.Aside from their industrial applications, PGEs are used in such other fields as health, consumer goods, and finance. Platinum, for example, is used in medical implants, such as pacemakers, and PGEs are used in cancer-fighting drugs. Platinum alloys are an ideal choice for jewelry because of their white color, strength, and resistance to tarnish. Platinum, palladium, and rhodium in the form of coins and bars are also used as investment commodities, and various financial instruments based on the value of these PGEs are traded on major exchanges

Induction of cell death by chemotherapeutic methylating agents

International Nuclear Information System (INIS)

Quiros Barrantes, Steve

2012-01-01

The mechanism of cell death induced by O 6 MeG has been investigated and inhibition of homologous recombination as a strategy for sensitization of tumor cells against methylating agents S N 1. Dependence of the cell cycle was determined toxic responses triggered by O''6 MeG and evaluated by proliferation assays if apoptotic cells have originated exclusively from the second post-treatment cycle. Dependence of O''6 MeG was found at DSB formation. The activation of the control points of the cell cycle and induction of apoptosis is generated during the second cell cycle. Additionally, a portion of the cells has been determined that triggers apoptosis in subsequent generations in the second cell cycle. Inhibition of homologous recombination has been a reasonable strategy to increase S N 1 alkylating agent effectiveness. Evidence has been provided in NHEJ dependent inhibition of DNA-PK that not significantly sensitizes the glioblastoma cells against temozolomide [es

Reversible, high molecular weight palladium and platinum coordination polymers based on phosphorus ligands

NARCIS (Netherlands)

Paulusse, J.M.J.; Huijbers, J.P.J.; Sijbesma, R.P.

2005-01-01

A general strategy for the preparation and characterization of high molecular weight coordination polymers based on bifunctional phosphorus ligands and palladium or platinum dichloride is described. Metal-to-ligand stoichiometry is of key importance for the formation of linear coordination polymers

Reversible, High Molecular Weight Palladium and Platinum Coordination Polymers Based on Phosphorus Ligands

NARCIS (Netherlands)

Paulusse, Jos Marie Johannes; Huijbers, Jeroen P.J.; Sijbesma, Rint P.

2005-01-01

A general strategy for the preparation and characterization of high molecular weight coordination polymers based on bifunctional phosphorus ligands and palladium or platinum dichloride is described. Metal-to-ligand stoichiometry is of key importance for the formation of linear coordination polymers

Comparison of platinum/MWCNTs Nanocatalysts Synthesis Processes for Proton Exchange Membrane Fuel Cells

Science.gov (United States)

Liu, Xuan

Due to the growing concerns on the depletion of petroleum based energy resources and climate change; fuel cell technologies have received much attention in recent years. Proton exchange membrane fuel cell (PEMFCs) features high energy conversion efficiency and nearly zero greenhouse gas emissions, because of its combination of the hydrogen oxidation reaction (HOR) at anode side and oxygen reduction reaction (ORR) at cathode side. Synthesis of Pt nanoparticles supported on multi walled carbon nanotubes (MWCNTs) possess a highly durable electrochemical surface area (ESA) and show good power output on proton exchange membrane (PEM) fuel cell performance. Platinum on multi-walled carbon nanotubes (MWCNTs) support were synthesized by two different processes to transfer PtCl62- from aqueous to organic phase. While the first method of Pt/MWCNTs synthesis involved dodecane thiol (DDT) and octadecane thiol (ODT) as anchoring agent, the second method used ammonium lauryl sulfate (ALS) as the dispersion/anchoring agent. The particle size and distribution of platinum were examined by high-resolution transmission electron microscope (HRTEM). The TEM images showed homogenous distribution and uniform particle size of platinum deposited on the surface of MWCNTs. The single cell fuel cell performance of the Pt/MWCNTs synthesized thiols and ALS based electrode containing 0.2 (anode) and 0.4 mg (cathode) Pt.cm-2 were evaluated using Nafion-212 electrolyte with H2 and O2 gases at 80 °C and ambient pressure. The catalyst synthesis with ALS is relatively simple compared to that with thiols and also showed higher performance (power density reaches about 1070 mW.cm -2). The Electrodes with Pt/MWCNTs nanocatalysts synthesized using ALS were characterized by cyclic voltammetry (CV) for durability evaluation using humidified H2 and N2 gases at room temperature (21 °C) along with commercial Pt/C for comparison. The ESA measured by cyclic voltammetry between 0.15 and 1.2 V showed significant

Multistage electrodeposition of supported platinum-based nanostructured systems for electrocatalytic applications

CSIR Research Space (South Africa)

Mkwizu, TS

2011-05-01

Full Text Available .R. Modibedi and Mkhulu K. Mathe* *kmathe@csir.co.za 219th ECS Meeting, 1 ? 6 May, 2011, Montreal, Canada Multistage Electrodeposition of Supported Platinum-based Nanostructured Systems for Electrocatalytic Applications Overview ? Acknowledgements... of constituent elements of the given electrode surface. ? Applications areas: Fuel cells, electrochemical sensors, electrolyzers Introduction e- A B 5 Introduction Atomic-level processes during electrocatalysis www...

Clinical developments of chemotherapeutic nanomedicines: Polymers and liposomes for delivery of camptothecins and platinum (II) drugs

KAUST Repository

Kieler-Ferguson, Heidi M.

2013-01-17

For the past 40 years, liposomal and polymeric delivery vehicles have been studied as systems capable of modulating the cytotoxicity of small molecule chemotherapeutics, increasing tumor bearing animal survival times, and improving drug targeting. Although a number of macromolecular-drug conjugates have progressed to clinical trials, tuning drug release to maintain efficacy in conjunction with controlling drug toxicity has prevented the clinical adoption of many vehicles. In this article, we review the motivations for and approaches to polymer and liposomal delivery with regard to camptothecin and cisplatin delivery. WIREs Nanomed Nanobiotechnol 2013, 5:130-138. doi: 10.1002/wnan.1209 For further resources related to this article, please visit the WIREs website. Conflict of interest: Drs Kieler-Ferguson and Fréchet declare no conflicts of interest. Dr Szoka is the founder of a liposome drug delivery company that is not working on any of the compounds mentioned in this article. © 2013 Wiley Periodicals, Inc.

Biotin-tagged platinum(iv) complexes as targeted cytostatic agents against breast cancer cells.

Science.gov (United States)

Muhammad, Nafees; Sadia, Nasreen; Zhu, Chengcheng; Luo, Cheng; Guo, Zijian; Wang, Xiaoyong

2017-09-05

A biotin-guided platinum IV complex is highly cytotoxic against breast cancer cells but hypotoxic against mammary epithelial cells. The mono-biotinylated Pt IV complex is superior to the di-biotinylated one and hence a promising drug candidate for the targeted therapy of breast cancer.

Rapid selection and proliferation of CD133+ cells from cancer cell lines: chemotherapeutic implications.

Directory of Open Access Journals (Sweden)

Sarah E Kelly

2010-04-01

Full Text Available Cancer stem cells (CSCs are considered a subset of the bulk tumor responsible for initiating and maintaining the disease. Several surface cellular markers have been recently used to identify CSCs. Among those is CD133, which is expressed by hematopoietic progenitor cells as well as embryonic stem cells and various cancers. We have recently isolated and cultured CD133 positive [CD133+] cells from various cancer cell lines using a NASA developed Hydrodynamic Focusing Bioreactor (HFB (Celdyne, Houston, TX. For comparison, another bioreactor, the rotary cell culture system (RCCS manufactured by Synthecon (Houston, TX was used. Both the HFB and the RCCS bioreactors simulate aspects of hypogravity. In our study, the HFB increased CD133+ cell growth from various cell lines compared to the RCCS vessel and to normal gravity control. We observed a +15-fold proliferation of the CD133+ cellular fraction with cancer cells that were cultured for 7-days at optimized conditions. The RCCS vessel instead yielded a (-4.8-fold decrease in the CD133+cellular fraction respect to the HFB after 7-days of culture. Interestingly, we also found that the hypogravity environment of the HFB greatly sensitized the CD133+ cancer cells, which are normally resistant to chemo treatment, to become susceptible to various chemotherapeutic agents, paving the way to less toxic and more effective chemotherapeutic treatment in patients. To be able to test the efficacy of cytotoxic agents in vitro prior to their use in clinical setting on cancer cells as well as on cancer stem cells may pave the way to more effective chemotherapeutic strategies in patients. This could be an important advancement in the therapeutic options of oncologic patients, allowing for more targeted and personalized chemotherapy regimens as well as for higher response rates.

Pharmacogenetic predictors of toxicity to platinum based chemotherapy in non-small cell lung cancer patients.

Science.gov (United States)

Pérez-Ramírez, Cristina; Cañadas-Garre, Marisa; Alnatsha, Ahmed; Villar, Eduardo; Delgado, Juan Ramón; Faus-Dáder, María José; Calleja-Hernández, Miguel Ÿngel

2016-09-01

Platinum-based chemotherapy is the standard treatment for NSCLC patients with EGFR wild-type, and as alternative to failure to EGFR inhibitors. However, this treatment is aggressive and most patients experience grade 3-4 toxicities. ERCC1, ERCC2, ERCC5, XRCC1, MDM2, ABCB1, MTHFR, MTR, SLC19A1, IL6 and IL16 gene polymorphisms may contribute to individual variation in toxicity to chemotherapy. The aim of this study was to evaluate the effect of these polymorphisms on platinum-based chemotherapy in NSCLC patients. A prospective cohorts study was conducted, including 141 NSCLC patients. Polymorphisms were analyzed by PCR Real-Time with Taqman(®) probes and sequencing. Patients with ERCC1 C118T-T allele (p=0.00345; RR=26.05; CI95%=4.33, 515.77) and ERCC2 rs50872-CC genotype (p=0.00291; RR=4.06; CI95%=1.66, 10.65) had higher risk of general toxicity for platinum-based chemotherapy. ERCC2 Asp312Asn G-alelle, ABCB1 C1236T-TT and the IL1B rs12621220-CT/TT genotypes conferred a higher risk to present multiple adverse events. The subtype toxicity analysis also revealed that ERCC2 rs50872-CC genotype (p=0.01562; OR=3.23; CI95%=1.29, 8.82) and IL16 rs7170924-T allele (p=0.01007; OR=3.19; CI95%=1.35, 7.97) were associated with grade 3-4 hematological toxicity. We did not found the influence of ERCC1 C8092A, ERCC2 Lys751Gln, ERCC2 Asp312Asn, ERCC5 Asp1104His, XRCC1 Arg194Trp, MDM2 rs1690924, ABCB1 C3435T, ABCB1 Ala893Ser/Thr, MTHFR A1298C, MTHFR C677T, IL1B rs1143623, IL1B rs16944, and IL1B rs1143627 on platinum-based chemotherapy toxicity. In conclusion, ERCC1 C118T, ERCC2 rs50872, ERCC2 Asp312Asn, ABCB1 C1236T, IL1B rs12621220 and IL16 rs7170924 polymorphisms may substantially act as prognostic factors in NSCLC patients treated with platinum-based chemotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cdt1 is differentially targeted for degradation by anticancer chemotherapeutic drugs.

Directory of Open Access Journals (Sweden)

Athanasia Stathopoulou

Full Text Available BACKGROUND: Maintenance of genome integrity is crucial for the propagation of the genetic information. Cdt1 is a major component of the pre-replicative complex, which controls once per cell cycle DNA replication. Upon DNA damage, Cdt1 is rapidly targeted for degradation. This targeting has been suggested to safeguard genomic integrity and prevent re-replication while DNA repair is in progress. Cdt1 is deregulated in tumor specimens, while its aberrant expression is linked with aneuploidy and promotes tumorigenesis in animal models. The induction of lesions in DNA is a common mechanism by which many cytotoxic anticancer agents operate, leading to cell cycle arrest and apoptosis. METHODOLOGY/PRINCIPAL FINDING: In the present study we examine the ability of several anticancer drugs to target Cdt1 for degradation. We show that treatment of HeLa and HepG2 cells with MMS, Cisplatin and Doxorubicin lead to rapid proteolysis of Cdt1, whereas treatment with 5-Fluorouracil and Tamoxifen leave Cdt1 expression unaffected. Etoposide affects Cdt1 stability in HepG2 cells and not in HeLa cells. RNAi experiments suggest that Cdt1 proteolysis in response to MMS depends on the presence of the sliding clamp PCNA. CONCLUSION/SIGNIFICANCE: Our data suggest that treatment of tumor cells with commonly used chemotherapeutic agents induces differential responses with respect to Cdt1 proteolysis. Information on specific cellular targets in response to distinct anticancer chemotherapeutic drugs in different cancer cell types may contribute to the optimization of the efficacy of chemotherapy.

SEM method for direct visual tracking of nanoscale morphological changes of platinum based electrocatalysts on fixed locations upon electrochemical or thermal treatments

Energy Technology Data Exchange (ETDEWEB)

Zorko, Milena [National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia); Centre of Excellence for Low-Carbon Technologies, Hajdrihova 19, Ljubljana (Slovenia); Jozinović, Barbara [Centre of Excellence for Low-Carbon Technologies, Hajdrihova 19, Ljubljana (Slovenia); Bele, Marjan [National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia); Centre of Excellence for Low-Carbon Technologies, Hajdrihova 19, Ljubljana (Slovenia); Hodnik, Nejc, E-mail: nejc.hodnik@ki.si [National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia); Gaberšček, Miran [National Institute of Chemistry, Hajdrihova 19, Ljubljana (Slovenia); Centre of Excellence for Low-Carbon Technologies, Hajdrihova 19, Ljubljana (Slovenia)

2014-05-01

A general method for tracking morphological surface changes on a nanometer scale with scanning electron microscopy (SEM) is introduced. We exemplify the usefulness of the method by showing consecutive SEM images of an identical location before and after the electrochemical and thermal treatments of platinum-based nanoparticles deposited on a high surface area carbon. Observations reveal an insight into platinum based catalyst degradation occurring during potential cycling treatment. The presence of chloride clearly increases the rate of degradation. At these conditions the dominant degradation mechanism seems to be the platinum dissolution with some subsequent redeposition on the top of the catalyst film. By contrast, at the temperature of 60 °C, under potentiostatic conditions some carbon corrosion and particle aggregation was observed. Temperature treatment simulating the annealing step of the synthesis reveals sintering of small platinum based composite aggregates into uniform spherical particles. The method provides a direct proof of induced surface phenomena occurring on a chosen location without the usual statistical uncertainty in usual, random SEM observations across relatively large surface areas. - Highlights: • A new SEM method for observations of identical locations. • Nanoscale morphological consecutive changes on identical locations. • Electrochemical and thermal treatments on platinum based nanoparticles. • Potential cycling induces platinum dissolution with redeposition on top of the film. • At 1.4 V vs. RHE and 60 °C carbon corrosion and particle aggregation is observed.

Adsorption and temperature-programmed desorption of hydrogen with dispersed platinum and platinum-gold catalysts

Energy Technology Data Exchange (ETDEWEB)

Anderson, J.R.; Foger, K.; Breakspere, R.J.

1979-05-01

Adsorption and temperature-programmed desorption of hydrogen with dispersed platinum and platinum-gold catalysts was studied with 0.9-3Vertical Bar3< platinum on silica gel, aerosil, sodium and lanthanum Y zeolites, and ..gamma..-alumina, and on aerosil-supported gold-platinum alloys containing 2, 10, 24, 33, and 85Vertical Bar3< gold. Surface enrichment with gold in the alloy systems, as derived from hydrogen adsorption data and predicted from surface enrichment theory and electron microscopic measurements of particle size, were in good agreement, which indicated that equilibrium was achieved by the thermal treatment (oxygen at 573/sup 0/K, hydrogen at 620/sup 0/K, repeated cycles) used. Hydrogen spillover to gold was observed at the higher hydrogen pressures tested on the alloys with high gold content, and to the zeolite supports. The temperature-programed desorption profiles were independent of gold content, which indicated that gold acts only as diluent, and that isolated surface platinum atoms become populated with hydrogen atoms either by hydrogen atom spillover from platinum ensembles to gold and from the gold to the isolated platinum, and/or by adsorption of a molecule directly on the isolated platinum and chemisorption of one H atom at an adjacent gold atom. The distribution of surface platinum ensembles was evaluated by a computer simulation method.

Platinum-Based Drugs Differentially Affect the Ultrastructure of Breast Cancer Cell Types

Directory of Open Access Journals (Sweden)

Shadia Al-Bahlani

2017-01-01

Full Text Available Breast cancer (BC is the most common cause of cancer-related death worldwide. Although platinum-based drugs (PBDs are effective anticancer agents, responsive patients eventually become resistant. While resistance of some cancers to PBDs has been explored, the cellular responses of BC cells are not studied yet. Therefore, we aim to assess the differential effects of PBDs on BC ultrastructure. Three representative cells were treated with different concentrations and timing of Cisplatin, Carboplatin, and Oxaliplatin. Changes on cell surface and ultrastructure were detected by scanning (SEM and transmission electron microscope (TEM. In SEM, control cells were semiflattened containing microvilli with extending lamellipodia while treated ones were round with irregular surface and several pores, indicating drug entry. Prolonged treatment resembled distinct apoptotic features such as shrinkage, membrane blebs, and narrowing of lamellipodia with blunt microvilli. TEM detected PBDs’ deposits that scattered among cellular organelles inducing structural distortion, lumen swelling, chromatin condensation, and nuclear fragmentation. Deposits were attracted to fat droplets, explained by drug hydrophobic properties, while later they were located close to cell membrane, suggesting drug efflux. Phagosomes with destructed organelles and deposits were detected as defending mechanism. Understanding BC cells response to PBDs might provide new insight for an effective treatment.

Prevention of blood transfusion with intravenous iron in gynecologic cancer patients receiving platinum-based chemotherapy.

Science.gov (United States)

Athibovonsuk, Punnada; Manchana, Tarinee; Sirisabya, Nakarin

2013-12-01

To compare the efficacy of intravenous iron and oral iron for prevention of blood transfusions in gynecologic cancer patients receiving platinum-based chemotherapy. Sixty-four non anemic gynecologic cancer patients receiving adjuvant platinum-based chemotherapy were stratified and randomized according to baseline hemoglobin levels and chemotherapy regimen. The study group received 200mg of intravenous iron sucrose immediately after each chemotherapy infusion. The control group received oral ferrous fumarate at a dose of 200mg three times a day. Complete blood count was monitored before each chemotherapy infusion. Blood transfusions were given if hemoglobin level was below 10mg/dl. There were 32 patients in each group. No significant differences in baseline hemoglobin levels and baseline characteristics were demonstrated between both groups. Nine patients (28.1%) in the study group and 18 patients (56.3%) in the control group required blood transfusion through 6 cycles of chemotherapy (p=0.02). Fewer median number of total packed red cell units were required in the study group compared to the control group (0 and 0.5 unit, respectively, p=0.04). Serious adverse events and hypersensitivity reactions were not reported. However, constipation was significantly higher in the control group (3.1% and 40.6%, p=gynecologic cancer patients receiving platinum-based chemotherapy, associated with less constipation than the oral formulation. © 2013 Elsevier Inc. All rights reserved.

Balancing repair and tolerance of DNA damage caused by alkylating agents.

Science.gov (United States)

Fu, Dragony; Calvo, Jennifer A; Samson, Leona D

2012-01-12

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for a favourable response of an organism to alkylating agents. Furthermore, the response of an individual to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity.

Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

Science.gov (United States)

Riad, Sandra; Bougherara, Habiba

2015-01-01

Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

Directory of Open Access Journals (Sweden)

Laila Ziko

2015-01-01

Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

Nanoengineering of Ruthenium and Platinum-based Nanocatalysts by Continuous-Flow Chemistry for Renewable Energy Applications

KAUST Repository

AlYami, Noktan Mohammed

2017-01-01

This thesis presents an integrated study of nanocatalysts for heterogenous catalytic and electrochemical processes using pure ruthenium (Ru) with mixed-phase and platinum-based nanomaterials synthesized by continuous-flow chemistry. There are three

Iron(III-salophene: an organometallic compound with selective cytotoxic and anti-proliferative properties in platinum-resistant ovarian cancer cells.

Directory of Open Access Journals (Sweden)

Thilo S Lange

2008-05-01

Full Text Available In this pioneer study to the biological activity of organometallic compound Iron(III-salophene (Fe-SP the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovarian cancer cell lines were investigated.Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma cell lines at concentrations between 100 nM and 1 microM, while the viability of HeLa cells (epithelial cervix adenocarcinoma or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed chromatin and chromatin fragmentation. Fe-SP treatment led to the activation of markers of the extrinsic (Caspase-8 and intrinsic (Caspase-9 pathway of apoptosis as well as of executioner Caspase-3 while PARP-1 was deactivated. Fe-SP exerted effects as an anti-proliferative agent with an IC(50 value of 300 nM and caused delayed progression of cells through S-phase phase of the cell cycle resulting in a complete S-phase arrest. When intra-peritoneally applied to rats Fe-SP did not show any systemic toxicity at concentrations that in preliminary trials were determined to be chemotherapeutic relevant doses in a rat ovarian cancer cell model.The present report suggests that Fe-SP is a potent growth-suppressing agent in vitro for cell lines derived from ovarian cancer and a potential therapeutic drug to treat such tumors in vivo.

The Paracrine Induction of TRAIL by Genotoxic Agents

National Research Council Canada - National Science Library

Spalding, Aaron

2002-01-01

TNF related apoptosis inducing ligand, TRAIL, is a recently cloned cytokine that has been shown to induce apoptosis in a synergistic fashion with chemotherapeutic agents on several cancer cell lines...

Multicenter retrospective study of cetuximab plus platinum-based chemotherapy for recurrent or metastatic oral squamous cell carcinoma.

Science.gov (United States)

Yanamoto, Souichi; Umeda, Masahiro; Kioi, Mitomu; Kirita, Tadaaki; Yamashita, Tetsuro; Hiratsuka, Hiroyoshi; Yokoo, Satoshi; Tanzawa, Hideki; Uzawa, Narikazu; Shibahara, Takahiko; Ota, Yoshihide; Kurita, Hiroshi; Okura, Masaya; Hamakawa, Hiroyuki; Kusukawa, Jingo; Tohnai, Iwai

2018-03-01

The purpose of this study was to assess the efficacy and safety of cetuximab plus platinum-based chemotherapy for patients specifically diagnosed with recurrent or metastatic oral squamous cell carcinoma (OSCC). We conducted a multicenter retrospective observational study of patients who underwent first-line cetuximab plus platinum-based chemotherapy between December 2012 and June 2015. 65 patients received weekly cetuximab (week 1, 400 mg/m 2 ; subsequent weeks, 250 mg/m 2 ) plus a maximum of six 3-weekly cycles of cisplatin (80 or 100 mg/m 2 , day 1) or carboplatin (at an area under the curve of 5 mg/mL/min as a 1-h intravenous infusion on day 1) and 5-fluorouracil (800 or 1000 mg/m 2 /day, days 1-4). Patients with stable disease who received cetuximab plus platinum-based chemotherapy continued to receive cetuximab until disease progression or unacceptable toxicities, whichever occurred first. The median follow-up was 10.5 (range 1.2-34.2) months. The best overall response and the disease control rates were 46.2 and 67.7%, respectively. The median overall survival and progression-free survival rates were 12.1 and 7.8 months, respectively. The most common grades 3-4 adverse events were skin rash (9.2%) followed by leukopenia (6.2%). None of the adverse events were fatal. The results of our multicenter retrospective study, which was the largest of its kind to date, suggest that first-line cetuximab plus platinum-based chemotherapy is suitable and well-tolerated for the systemic therapy of recurrent or metastatic OSCC.

Panitumumab and pegylated liposomal doxorubicin in platinum-resistant epithelial ovarian cancer with KRAS wild-type

DEFF Research Database (Denmark)

Steffensen, Karina Dahl; Waldstrøm, Marianne; Pallisgård, Niels

2013-01-01

OBJECTIVE: The increasing number of negative trials for ovarian cancer treatment has prompted an evaluation of new biologic agents, which in combination with chemotherapy may improve survival. The aim of this study was to investigate the response rate in platinum-resistant, KRAS wild-type ovarian...... cancer patients treated with pegylated liposomal doxorubicin (PLD) supplemented with panitumumab. PATIENTS AND METHODS: Major eligibility criteria were relapsed ovarian/fallopian/peritoneal cancer patients with platinum-resistant disease, measurable disease by GCIG CA125 criteria and KRAS wild-type...

Delivery of chemotherapeutics across the blood-brain barrier: challenges and advances.

Science.gov (United States)

Doolittle, Nancy D; Muldoon, Leslie L; Culp, Aliana Y; Neuwelt, Edward A

2014-01-01

The blood-brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2-26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. © 2014 Elsevier Inc. All rights reserved.

Delivery of Chemotherapeutics Across the Blood–Brain Barrier: Challenges and Advances

Science.gov (United States)

Doolittle, Nancy D.; Muldoon, Leslie L.; Culp, Aliana Y.; Neuwelt, Edward A.

2017-01-01

The blood–brain barrier (BBB) limits drug delivery to brain tumors. We utilize intraarterial infusion of hyperosmotic mannitol to reversibly open the BBB by shrinking endothelial cells and opening tight junctions between the cells. This approach transiently increases the delivery of chemotherapy, antibodies, and nanoparticles to brain. Our preclinical studies have optimized the BBB disruption (BBBD) technique and clinical studies have shown its safety and efficacy. The delivery of methotrexate-based chemotherapy in conjunction with BBBD provides excellent outcomes in primary central nervous system lymphoma (PCNSL) including stable or improved cognitive function in survivors a median of 12 years (range 2–26 years) after diagnosis. The addition of rituximab to chemotherapy with BBBD for PCNSL can be safely accomplished with excellent overall survival. Our translational studies of thiol agents to protect against platinum-induced toxicities led to the development of a two-compartment model in brain tumor patients. We showed that delayed high-dose sodium thiosulfate protects against carboplatin-induced hearing loss, providing the framework for large cooperative group trials of hearing chemoprotection. Neuroimaging studies have identified that ferumoxytol, an iron oxide nanoparticle blood pool agent, appears to be a superior contrast agent to accurately assess therapy-induced changes in brain tumor vasculature, in brain tumor response to therapy, and in differentiating central nervous system lesions with inflammatory components. This chapter reviews the breakthroughs, challenges, and future directions for BBBD. PMID:25307218

A retrospective evaluation of activity of gemcitabine/platinum regimens in the treatment of recurrent ovarian cancer

Directory of Open Access Journals (Sweden)

Tran N. Le

2017-11-01

Full Text Available Abstract Background While many of these agents have been compared in prospective clinical trials, the gemcitabine/platinumbased regimens have not been compared in a prospective, randomized clinical trial. While bothgemcitabine/carboplatin and gemcitabine/cisplatin have a similar ORR in separate clinical trials, the tworegimens have never been directly been compared. With overlapping dose-limiting toxicity of thrombocytopenia, the gemcitabine/carboplatin regimen has been challenging to employ in the clinical setting in previously treated ovarian cancer patients and is often associated with treatment delays and/or dose reductions. Gemcitabine/cisplatin can also be a challenge due to its dose limiting neuropathy and renal toxicity, especially in previously treated patients. In the absence of any prospective, head to head comparison this retrospective study was embarked upon to compare the response rate and toxicity profiles of gemcitabine/cisplatin verses gemcitabine/carboplatin for the treatment of platinum-sensitive verses platinum-resistant recurrent ovarian cancer. Methods This was a retrospective chart review study that identified patients that had received either gemcitabine/cisplatin or gemcitabine/carboplatin for treatment of recurrent ovarian cancer and compared documented hematological and non-hematological toxicity and response based on RECIST (v1.1. Data was evaluated based upon platinum sensitivity/resistance as well. Results A total of 93 patients were identified that had received a gemcitabine/platinum regimen with 48 with recurrent ovarian cancer that were included in the study. There were 21 patients in the gemcitabine/cisplatin arm and 27 patients identified in the gemcitabine/carboplatin arm. Objective response rate (ORR was greater in platinum-sensitive patients that received gemcitabine/carboplatin compared to gemcitabine/cisplatin (8 (67% vs 2 (25%, p < 0.05. Conversely, ORR was greater in platinum-resistant patients treated

In vitro effects of platinum compounds on renal cellular respiration in mice.

Science.gov (United States)

Almarzooqi, Saeeda-S; Alfazari, Ali-S; Abdul-Kader, Hidaya-M; Saraswathiamma, Dhanya; Albawardi, Alia-S; Souid, Abdul-Kader

2015-01-01

Cisplatin, carboplatin and oxaliplatin are structurally-related compounds, which are commonly used in cancer therapy. Cisplatin (Platinol(®)) has Boxed Warning stating: "Cumulative renal toxicity associated with PLATINOL is severe", while carboplatin and oxaliplatin are less nephrotoxic. These drugs form platinum adducts with cellular DNA. Their bindings to cellular thiols (e.g., glutathione and metallothionein) are known to contribute to drug resistance while thiol depletion augments platinum toxicity. Using phosphorescence oxygen analyzer, this study investigated the effects of platinum drugs on renal cellular respiration (mitochondrial O2 consumption) in the presence and absence of the thiol blocking agent N-ethylmaleimide (used here as a model for thiol depletion). Renal cellular ATP was also determined. Kidney fragments from C57BL/6 mice were incubated at 37 °C in Krebs-Henseleit buffer (gassed with 95% O2:5% CO2) with and without 100 μM platinum drug in the presence and absence of 100 μM N-ethylmaleimide for ≤ 6 h. Platinum drugs alone had no effects on cellular respiration (P ≥ 0.143) or ATP (P ≥ 0.161). N-ethylmaleimide lowered cellular respiration (P ≤ 0.114) and ATP (P = 0.008). The combination of platinum drug and N-ethylmaleimide significantly lowered both cellular respiration (P ≤ 0.006) and ATP (P ≤ 0.003). Incubations with N-ethylmaleimide alone were associated with moderate-to-severe tubular necrosis. Incubations with cisplatin+N-ethylmaleimide vs. cisplatin alone produced similar severities of tubular necrosis. Tubular derangements were more prominent in carboplatin+N-ethylmaleimide vs. carboplatin alone and in oxaliplatin+N-ethylmaleimide vs. oxaliplatin alone. These results demonstrate the adverse events of thiol depletion on platinum-induced nephrotoxicities. The results suggest cellular bioenergetics is a useful surrogate biomarker for assessing drug-induced nephrotoxicities.

A combined radiation and platinum chemotherapy for esophageal carcinoma

International Nuclear Information System (INIS)

Takamura, Akio; Saito, Hiroya; Sakurai, Yasuo; Horio, Keiji; Mizoe, Junetsu.

1993-01-01

The prognosis of the patients with advanced esophageal carcinoma treated by definitive radiotherapy is still dismal with a reported 5-year survival rate of 5-10% in most series. Since 1986, combined radiotherapy with chemotherapy using platinum analogue was initiated at Asahikawa and Obihiro Kosei Hospitals in order to improve local-regional control and the survival of the patients. From 1980 to 1992, 81 patients with unresectable esophageal carcinoma were treated with radiotherapy. Since April 1986, 37 out of the 81 patients received both radiotherapy and chemotherapy with platinum. Platinum was used during the course of radiotherapy. The method of administration of platinum was as follows; Cisplatin intravenously (50 mg, weekly, total 200 mg) in 9 patients, Carboplatin intravenously (100-150 mg, weekly, total 400-900 mg) in 11 patients and Cisplatin intraarterially (100 mg, at a 3-4 week interval, total 100-300 mg) in 17 patients. These 37 patients (Group A) were compared to 44 patients treated by radiotherapy alone (Group B) with respect to initial response and survival rate. Response was defined according to the guidelines recommended by Japanese Society for Esophageal Diseases. Response rates were 59.1% (19 CR and 7 PR) in Group B and 70.3% (7 CR and 19 PR) in Group A. Primary relapse-free rates were 36.4% in Group B and 37.8% in Group A. The cumulative survival at 3 years were 11.7% in Group B and 10.6% in Group A. Enhancement of side effects by chemotherapy was minimal and acceptable. Improvement of local-regional control and survival was not obvious by adding a concomitant platinum-chemotherapy. A definite conclusion, however, could not be drawn because of the retrospective, non-controlled nature of this study. Introduction of more intensive, multiple agents chemotherapy seems necessary if one aims at improving the results. (author)

Chemotherapy-induced pulmonary hypertension: role of alkylating agents.

Science.gov (United States)

Ranchoux, Benoît; Günther, Sven; Quarck, Rozenn; Chaumais, Marie-Camille; Dorfmüller, Peter; Antigny, Fabrice; Dumas, Sébastien J; Raymond, Nicolas; Lau, Edmund; Savale, Laurent; Jaïs, Xavier; Sitbon, Olivier; Simonneau, Gérald; Stenmark, Kurt; Cohen-Kaminsky, Sylvia; Humbert, Marc; Montani, David; Perros, Frédéric

2015-02-01

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension (PH) characterized by progressive obstruction of small pulmonary veins and a dismal prognosis. Limited case series have reported a possible association between different chemotherapeutic agents and PVOD. We evaluated the relationship between chemotherapeutic agents and PVOD. Cases of chemotherapy-induced PVOD from the French PH network and literature were reviewed. Consequences of chemotherapy exposure on the pulmonary vasculature and hemodynamics were investigated in three different animal models (mouse, rat, and rabbit). Thirty-seven cases of chemotherapy-associated PVOD were identified in the French PH network and systematic literature analysis. Exposure to alkylating agents was observed in 83.8% of cases, mostly represented by cyclophosphamide (43.2%). In three different animal models, cyclophosphamide was able to induce PH on the basis of hemodynamic, morphological, and biological parameters. In these models, histopathological assessment confirmed significant pulmonary venous involvement highly suggestive of PVOD. Together, clinical data and animal models demonstrated a plausible cause-effect relationship between alkylating agents and PVOD. Clinicians should be aware of this uncommon, but severe, pulmonary vascular complication of alkylating agents. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Lysosomes as mediators of drug resistance in cancer.

Science.gov (United States)

Zhitomirsky, Benny; Assaraf, Yehuda G

2016-01-01

Drug resistance remains a leading cause of chemotherapeutic treatment failure and cancer-related mortality. While some mechanisms of anticancer drug resistance have been well characterized, multiple mechanisms remain elusive. In this respect, passive ion trapping-based lysosomal sequestration of multiple hydrophobic weak-base chemotherapeutic agents was found to reduce the accessibility of these drugs to their target sites, resulting in a markedly reduced cytotoxic effect and drug resistance. Recently we have demonstrated that lysosomal sequestration of hydrophobic weak base drugs triggers TFEB-mediated lysosomal biogenesis resulting in an enlarged lysosomal compartment, capable of enhanced drug sequestration. This study further showed that cancer cells with an increased number of drug-accumulating lysosomes are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. In addition to passive drug sequestration of hydrophobic weak base chemotherapeutics, other mechanisms of lysosome-mediated drug resistance have also been reported; these include active lysosomal drug sequestration mediated by ATP-driven transporters from the ABC superfamily, and a role for lysosomal copper transporters in cancer resistance to platinum-based chemotherapeutics. Furthermore, lysosomal exocytosis was suggested as a mechanism to facilitate the clearance of chemotherapeutics which highly accumulated in lysosomes, thus providing an additional line of resistance, supplementing the organelle entrapment of chemotherapeutics away from their target sites. Along with these mechanisms of lysosome-mediated drug resistance, several approaches were recently developed for the overcoming of drug resistance or exploiting lysosomal drug sequestration, including lysosomal photodestruction and drug-induced lysosomal membrane permeabilization. In this review we explore the current literature addressing the role of lysosomes in mediating cancer drug

The development of platinum-based alloys and their thermodynamic database

Directory of Open Access Journals (Sweden)

Cornish L.A.

2002-01-01

Full Text Available A series of quaternary platinum-based alloys have been demonstrated to exhibit the same two-phase structure as Ni-based superalloys and showed good mechanical properties. The properties of ternary alloys were a good indication that the quaternary alloys, with their better microstructure, will be even better. The quaternary alloy composition has been optimised at Pt84:Al11:Ru2:Cr3 for the best microstructure and hardness. Work has begun on establishing a thermodynamic database for Pt-Al-Ru-Cr alloys, and further work will be done to enhance the mechanical and oxidation properties of the alloys by adding small amounts of other elements to the base composition of Pt84:Al11:Ru2:Cr3.

Mild in situ growth of platinum nanoparticles on multiwalled carbon nanotube-poly (vinyl alcohol) hydrogel electrode for glucose electrochemical oxidation

Energy Technology Data Exchange (ETDEWEB)

Liu, Shumin; Zheng, Yudong, E-mail: zhengyudong@mater.ustb.edu.cn; Qiao, Kun [University of Science and Technology Beijing, School of Material Science and Engineering (China); Su, Lei [University of Science and Technology Beijing, School of Chemistry and Biological Engineering (China); Sanghera, Amendeep; Song, Wenhui [University College London, UCL Centre for Nanotechnology & Regenerative Medicine, Division of Surgery and Interventional Science (United Kingdom); Yue, Lina; Sun, Yi [University of Science and Technology Beijing, School of Material Science and Engineering (China)

2015-12-15

This investigation describes an effective strategy to fabricate an electrochemically active hybrid hydrogel made from platinum nanoparticles that are highly dense, uniformly dispersed, and tightly embedded throughout the conducting hydrogel network for the electrochemical oxidation of glucose. A suspension of multiwalled carbon nanotubes and polyvinyl alcohol aqueous was coated on glassy carbon electrode by electrophoretic deposition and then physically crosslinked to form a three-dimensional porous conductive hydrogel network by a process of freezing and thawing. The network offered 3D interconnected mass-transport channels (around 200 nm) and confined nanotemplates for in situ growth of uniform platinum nanoparticles via the moderate reduction agent, ascorbic acid. The resulting hybrid hydrogel electrode membrane demonstrates an effective method for loading platinum nanoparticles on multiwalled carbon nanotubes by the electrostatic adsorption between multiwalled carbon nanotubes and platinum ions within porous hydrogel network. The average diameter of platinum nanoparticles is 37 ± 14 nm, which is less than the particle size by only using the moderate reduction agent. The hybrid hydrogel electrode membrane-coated glassy carbon electrode showed excellent electrocatalytic activity and good long-term stability toward glucose electrochemical oxidation. The glucose oxidation current exhibited a linear relationship with the concentration of glucose in the presence of chloride ions, promising for potential applications of implantable biofuel cells, biosensors, and electronic devices.

Carbon nanotube/platinum nanoparticle nanocomposites: preparation, characterization and application in electro oxidation of alcohols

International Nuclear Information System (INIS)

Kalinke, Adir H.; Zarbin, Aldo J. G.

2014-01-01

The synthesis and characterization of different platinum nanoparticle/ carbon nanotube nanocomposite samples are described along with the application of these nanocomposites as electrocatalysts for alcohol oxidation. Samples were prepared by a biphasic system in which platinum nanoparticles (Pt-NPs) are synthesized in situ in contact with a carbon nanotube (CNT) dispersion. Variables including platinum precursor/CNT ratio, previous chemical treatment of carbon nanotubes, and presence or absence of a capping agent were evaluated and correlated with the characteristic of the synthesized materials. Samples were characterized by Raman spectroscopy, X-ray diffraction, thermogravimetric analysis and transmission electron microscopy. Glassy carbon electrodes were modified by the nanocomposite samples and evaluated as electrocatalysts for alcohol oxidation. Current densities of 56.1 and 79.8/104.7 mA cm -2 were determined for the oxidation of methanol and ethanol, respectively. (author)

SEM method for direct visual tracking of nanoscale morphological changes of platinum based electrocatalysts on fixed locations upon electrochemical or thermal treatments.

Science.gov (United States)

Zorko, Milena; Jozinović, Barbara; Bele, Marjan; Hodnik, Nejc; Gaberšček, Miran

2014-05-01

A general method for tracking morphological surface changes on a nanometer scale with scanning electron microscopy (SEM) is introduced. We exemplify the usefulness of the method by showing consecutive SEM images of an identical location before and after the electrochemical and thermal treatments of platinum-based nanoparticles deposited on a high surface area carbon. Observations reveal an insight into platinum based catalyst degradation occurring during potential cycling treatment. The presence of chloride clearly increases the rate of degradation. At these conditions the dominant degradation mechanism seems to be the platinum dissolution with some subsequent redeposition on the top of the catalyst film. By contrast, at the temperature of 60°C, under potentiostatic conditions some carbon corrosion and particle aggregation was observed. Temperature treatment simulating the annealing step of the synthesis reveals sintering of small platinum based composite aggregates into uniform spherical particles. The method provides a direct proof of induced surface phenomena occurring on a chosen location without the usual statistical uncertainty in usual, random SEM observations across relatively large surface areas. Copyright © 2014 Elsevier B.V. All rights reserved.

Agent Programming Languages and Logics in Agent-Based Simulation

DEFF Research Database (Denmark)

Larsen, John

2018-01-01

and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI...

Reactions of neopentane and neohexane on platinum/Y-zeolite and platinum/silica catalysts

Energy Technology Data Exchange (ETDEWEB)

Foger, K.; Anderson, J.R.

1978-10-13

The hydrocracking/hydroisomerization reaction of 20:1 hydrogen/neopentane at 455-625/sup 0/K was studied on platinum-exchanged sodium, calcium, and lanthanum Y zeolites and Aerosil-supported platinum of 1-20 nm average platinum particle size, by analysis of the product distribution, ESCA, and temperature-programed desorption. The results suggested that the reaction occurs only on platinum and that it proceeds by two parallel pathways which have different activation energies and whose relative proportion depends on the particle size. One pathway is the conventionally accepted one on low-index crystallite facets; the other proceeds on single-surface platinum atoms of low coordination (corner or edge atoms) which become more abundant at lower crystallite size. In both cases, the adsorbed intermediate may undergo either isomerization or hydrogenolysis; the selectivity depends on the hydrogen partial pressure and the relative strength of adsorption of hydrogen and neopentane. Neohexane isomerization selectivity on the same catalysts is consistent with a carbonium ion mechanism on a dual-function catalyst.

[Alkylating agents].

Science.gov (United States)

Pourquier, Philippe

2011-11-01

With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

Rhenium–platinum antitumor systems

Directory of Open Access Journals (Sweden)

A. V. Shtemenko

2017-04-01

Full Text Available This review provides an overlook of design (in short, antitumor and other biological activity of quadruple-bonded cluster dirhenium(III compounds and their synergism with cisplatin. In particular, we describe the work of the rhenium-platinum antitumor system (introduction of rhenium and platinum compounds. Among known metal-based anticancer drugs and drug candidates dirhenium(III compounds differ profoundly due to their strong antiradical and antioxidant properties determined by quadruple bond unsaturation. Such advantages of metal complexes as more expressed redox chemical propertie should be exploited for creating more efficient anticancer drugs. Combination of drugs leads to synergistic effects and/or to lowe­ring toxicity of platinides and is very promising in cancer chemotherapy. The review covers the follo­wing items: design of quadruple bonded dirhenium(III clusters, their spectral and antiradical properties (in short; interaction of the dirhenium(III compounds with lipids and formation of liposomes; interaction of the dirhenium(III compounds with erythrocytes and their antihemolytic activity in the models of hemolytic anemia; anticancer activity of dirhenium clusters and work of the rhenium-platinum antitumor system; antianemic and antioxidant properties of the dirhenium(III compounds in the model of tumor growth; interaction of the dirhenium(III compounds with nucleobases and DNA. Some modern trends in the field of bioinorganic and medicinal chemi­stry are also considered regarding their connection to the rhenium-platinum system efficiency: use of combinational therapy and nanomaterials; involvement of some biologically active ligands and redox-activation strategy, etc.

Synthesis of platinum nanowire networks using a soft template.

Science.gov (United States)

Song, Yujiang; Garcia, Robert M; Dorin, Rachel M; Wang, Haorong; Qiu, Yan; Coker, Eric N; Steen, William A; Miller, James E; Shelnutt, John A

2007-12-01

Platinum nanowire networks have been synthesized by chemical reduction of a platinum complex using sodium borohydride in the presence of a soft template formed by cetyltrimethylammonium bromide in a two-phase water-chloroform system. The interconnected polycrystalline nanowires possess the highest surface area (53 +/- 1 m2/g) and electroactive surface area (32.4 +/- 3.6 m2/g) reported for unsupported platinum nanomaterials; the high surface area results from the small average diameter of the nanowires (2.2 nm) and the 2-10 nm pores determined by nitrogen adsorption measurements. Synthetic control over the network was achieved simply by varying the stirring rate and reagent concentrations, in some cases leading to other types of nanostructures including wormlike platinum nanoparticles. Similarly, substitution of a palladium complex for platinum gives palladium nanowire networks. A mechanism of formation of the metal nanowire networks is proposed based on confined metal growth within a soft template consisting of a network of swollen inverse wormlike micelles.

Hypertension induced by chemotherapeutic and immunosuppresive agents: a new challenge.

Science.gov (United States)

Abi Aad, Simon; Pierce, Matthew; Barmaimon, Guido; Farhat, Fadi S; Benjo, Alexandre; Mouhayar, Elie

2015-01-01

Hypertension is a common adverse effect of certain anti neoplastic therapy. The incidence and severity of hypertension are dependent mainly on the type and the dose of the drug. We reviewed the literature for studies that reported the effect of anti neoplastic agents on blood pressure in patients with malignancies. The medical databases of PubMed, MEDLINE and EMBASE were searched for articles published in English between 1955 and June 2012. The effects of specific agents on blood pressure were analyzed. Hypertension is a prevalent adverse effect of many of the new chemotherapy agents such as VEGF inhibitors. Approximately 30% of patients treated for cancer will have concomitant hypertension, and crucial chemotherapy can sometimes be stopped due to new onset or worsening severe hypertension. The importance of a timely diagnosis and optimal management of HTN in this group of patients is related to the facts that HTN is a well established risk factor for chemotherapy-induced cardiotoxicity and if left untreated, can alter cancer management and result in dose reductions or termination of anti-cancer treatments as well as life-threatening end organ damage. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Platinum-group metals from nuclear reactions as a possible resource

International Nuclear Information System (INIS)

Jensen, G.A.

1985-03-01

Spent nuclear fuels contain significant quantities of three of the platinum-group metals (ruthenium, rhodium, and palladium), and a related element technetium, which is nearly absent in nature. Applications for ruthenium, rhodium, and palladium are well established. Since the supply of these and other platinum metals is largely from foreign sources, they are considered strategic materials. Existing and future spent nuclear fuels contain quantities of these platinum metals that exceed the United States reserve base. Technetium has properties similar to platinum metals and has unique, useful properties of its own. The technical feasibility of recovering and using fission product platinum metals (and technetium) extensively in industry depends on: thoroughly decontaminating platinum-group metals from all other radioactive materials in the waste stream; separating platinum-group metals from one another in very high purity; using applications where appropriate control of the residual radioactivity is possible; and whether or not the United States will recover or process spent fuel prior to repository storage. If the radioactivity must be removed, isotope separation or long term storage to allow decay of the contained radioisotopes may be possible. 7 figs., 7 tabs

Improvement of a predictive model in ovarian cancer patients submitted to platinum-based chemotherapy: implications of a GST activity profile.

Science.gov (United States)

Pereira, Deolinda; Assis, Joana; Gomes, Mónica; Nogueira, Augusto; Medeiros, Rui

2016-05-01

The success of chemotherapy in ovarian cancer (OC) is directly associated with the broad variability in platinum response, with implications in patients survival. This heterogeneous response might result from inter-individual variations in the platinum-detoxification pathway due to the expression of glutathione-S-transferase (GST) enzymes. We hypothesized that GSTM1 and GSTT1 polymorphisms might have an impact as prognostic and predictive determinants for OC. We conducted a hospital-based study in a cohort of OC patients submitted to platinum-based chemotherapy. GSTM1 and GSTT1 genotypes were determined by multiplex PCR. GSTM1-null genotype patients presented a significantly longer 5-year survival and an improved time to progression when compared with GSTM1-wt genotype patients (log-rank test, P = 0.001 and P = 0.013, respectively). Multivariate Cox regression analysis indicates that the inclusion of genetic information regarding GSTM1 polymorphism increased the predictive ability of risk of death after OC platinum-based chemotherapy (c-index from 0.712 to 0.833). Namely, residual disease (HR, 4.90; P = 0.016) and GSTM1-wt genotype emerged as more important predictors of risk of death (HR, 2.29; P = 0.039; P = 0.036 after bootstrap). No similar effect on survival was observed regarding GSTT1 polymorphism, and there were no statistically significant differences between GSTM1 and GSTT1 genotypes and the assessed patients' clinical-pathological characteristics. GSTM1 polymorphism seems to have an impact in OC prognosis as it predicts a better response to platinum-based chemotherapy and hence an improved survival. The characterization of the GSTM1 genetic profile might be a useful molecular tool and a putative genetic marker for OC clinical outcome.

Cis-diamminedichloride platinum II (DDP) in the treatment of penile carcinoma.

Science.gov (United States)

Sklaroff, R B; Yagoda, A

1979-11-01

Cis-diamminedichloride platinum II (DDP) was administered to eight patients with epidermoid carcinoma of the penis. Three of six adequately treated patients had an objective response: one patient achieved complete remission of 7 months duration and 2 patients had partial remissions of 8 and 2 months, respectively. DDP appears to be an active agent in the treatment of penile carcinoma.

Inhibition of phosphatidylinositol 3-kinase promotes tumor cell resistance to chemotherapeutic agents via a mechanism involving delay in cell cycle progression

International Nuclear Information System (INIS)

McDonald, Gail T.; Sullivan, Richard; Pare, Genevieve C.; Graham, Charles H.

2010-01-01

Approaches to overcome chemoresistance in cancer cells have involved targeting specific signaling pathways such as the phosphatidylinositol 3-kinase (PI3K) pathway, a stress response pathway known to be involved in the regulation of cell survival, apoptosis and growth. The present study determined the effect of PI3K inhibition on the clonogenic survival of human cancer cells following exposure to various chemotherapeutic agents. Treatment with the PI3K inhibitors LY294002 or Compound 15e resulted in increased survival of MDA-MB-231 breast carcinoma cells after exposure to doxorubicin, etoposide, 5-fluorouracil, and vincristine. Increased survival following PI3K inhibition was also observed in DU-145 prostate, HCT-116 colon and A-549 lung carcinoma cell lines exposed to doxorubicin. Increased cell survival mediated by LY294002 was correlated with a decrease in cell proliferation, which was linked to an increase in the proportion of cells in the G 1 phase of the cell cycle. Inhibition of PI3K signaling also resulted in higher levels of the cyclin-dependent kinase inhibitors p21 Waf1/Cip1 and p27 Kip1 ; and knockdown of p27 kip1 with siRNA attenuated resistance to doxorubicin in cells treated with LY294002. Incubation in the presence of LY294002 after exposure to doxorubicin resulted in decreased cell survival. These findings provide evidence that PI3K inhibition leads to chemoresistance in human cancer cells by causing a delay in cell cycle; however, the timing of PI3K inhibition (either before or after exposure to anti-cancer agents) may be a critical determinant of chemosensitivity.

A CSP-Based Agent Modeling Framework for the Cougaar Agent-Based Architecture

Science.gov (United States)

Gracanin, Denis; Singh, H. Lally; Eltoweissy, Mohamed; Hinchey, Michael G.; Bohner, Shawn A.

2005-01-01

Cognitive Agent Architecture (Cougaar) is a Java-based architecture for large-scale distributed agent-based applications. A Cougaar agent is an autonomous software entity with behaviors that represent a real-world entity (e.g., a business process). A Cougaar-based Model Driven Architecture approach, currently under development, uses a description of system's functionality (requirements) to automatically implement the system in Cougaar. The Communicating Sequential Processes (CSP) formalism is used for the formal validation of the generated system. Two main agent components, a blackboard and a plugin, are modeled as CSP processes. A set of channels represents communications between the blackboard and individual plugins. The blackboard is represented as a CSP process that communicates with every agent in the collection. The developed CSP-based Cougaar modeling framework provides a starting point for a more complete formal verification of the automatically generated Cougaar code. Currently it is used to verify the behavior of an individual agent in terms of CSP properties and to analyze the corresponding Cougaar society.

Balancing repair and tolerance of DNA damage caused by alkylating agents

OpenAIRE

Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D.

2012-01-01

Alkylating agents constitute a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER) and mismatch repair (MMR), respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial ...

Nanoparticulate platinum films on gold using dendrimer-based wet ...

Indian Academy of Sciences (India)

Central Electrochemical Research Institute, Karaikudi 630 006, India. E-mail: ... deposition methods for applications involving thin films, e.g., catalysis. Deposition of platinum .... The spectrum recorded at 0.3 V shows a mixed control behaviour ...

Hydrogenation of hexene over platinum on alumina vs. platinum in a Na-Y zeolite

International Nuclear Information System (INIS)

Miner, R.S. Jr.; Ione, K.G.; Namba, S.; Turkevich, J.

1978-01-01

In order to study the efficacy of zeolites as supports, several platinum H--Y zeolites were prepared by ion exchanging an H--Y zeolite with Pt(NH 3 ) 4 Cl 2 and reducing these products with hydrazine hydrate (A, B, C). Another preparation was made by adsorbing 32-A platinum sol on the zeolite crystallites (D). These catalysts were studied for hydrogenation and isomerization of hexene-1, ethylene hydrogenation, hydrogen chemisorption, and poison titration. They were compared with monodisperse Pt (32 A diameter) on alumina. A marked difference was found between the behavior of hexene-1 with the platinum-in-zeolite and with the platinum-on-alumina

Diameter-dependent release of a cisplatin pro-drug from small and large functionalized carbon nanotubes

Science.gov (United States)

Muzi, Laura; Ménard-Moyon, Cécilia; Russier, Julie; Li, Jian; Chin, Chee Fei; Ang, Wee Han; Pastorin, Giorgia; Risuleo, Gianfranco; Bianco, Alberto

2015-03-01

The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes' inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(iv) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(iv)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(iv)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(iv)@CNT exposure demonstrate that they can

Phosphoric acid fuel cell platinum use study

Science.gov (United States)

Lundblad, H. L.

1983-05-01

The U.S. Department of Energy is promoting the private development of phosphoric acid fuel cell (PAFC) power plants for terrestrial applications. Current PAFC technology utilizes platinum as catalysts in the power electrodes. The possible repercussions that the platinum demand of PAFC power plant commercialization will have on the worldwide supply and price of platinum from the outset of commercialization to the year 2000 are investigated. The platinum demand of PAFC commercialization is estimated by developing forecasts of platinum use per unit of generating capacity and penetration of PAFC power plants into the electric generation market. The ability of the platinum supply market to meet future demands is gauged by assessing the size of platinum reserves and the capability of platinum producers to extract, refine and market sufficient quantities of these reserves. The size and timing of platinum price shifts induced by the added demand of PAFC commercialization are investigated by several analytical methods. Estimates of these price shifts are then used to calculate the subsequent effects on PAFC power plant capital costs.

Nanoengineering of Ruthenium and Platinum-based Nanocatalysts by Continuous-Flow Chemistry for Renewable Energy Applications

KAUST Repository

AlYami, Noktan Mohammed

2017-04-15

This thesis presents an integrated study of nanocatalysts for heterogenous catalytic and electrochemical processes using pure ruthenium (Ru) with mixed-phase and platinum-based nanomaterials synthesized by continuous-flow chemistry. There are three major challenges to the application of nanomaterials in heterogenous catalytic reactions and electrocatalytic processes in acidic solution. These challenges are the following: (i) controlling the size, shape and crystallography of nanoparticles to give the best catalytic properties, (ii) scaling these nanoparticles up to a commercial quantity (kg per day) and (iii) making stable nanoparticles that can be used catalytically without degrading in acidic electrolytes. Some crucial limitations of these nanostructured materials in energy conversion and storage applications were overcome by continuous-flow chemistry. By using a continuous-flow reactor, the creation of scalable nanoparticle systems was achieved and their functionality was modified to control the nanoparticles’ physical and chemical characteristics. The nanoparticles were also tested for long-term stability, to make sure these nanoparticles were feasible under realistic working conditions. These nanoparticles are (1) shape- and crystallography-controlled ruthenium (Ru) nanoparticles, (2) size-controlled platinum-metal (Pt-M= nickel (Ni) & copper (Cu)) nanooctahedra (while maintaining morphology) and (3) core-shell platinum@ruthenium (Pt@Ru) nanoparticles where an ultrathin ruthenium shell was templated onto the platinum core. Thus, a complete experimental validation of the formation of a scalable amount of these nanoparticles and their catalytic activity and stability towards the oxygen evolution reaction (OER) in acid medium, hydrolysis of ammonia borane (AB) along with plausible explanations were provided.

Phase I trials of WR2721 in combination with radiation therapy and with the alkylating agents cyclophosphamide and cis-platinum

Energy Technology Data Exchange (ETDEWEB)

Kligerman, M.M.; Blumberg, A.L.; Glick, J.H.; Nelson, D.F.; Glover, D.; Yuhas, J.M.; Amols, H.I.; Goodman, R.L.

Three phase I trials of the radioprotector S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721) have accessed 60 patients. Study 1 is devised to determine the maximum tolerated dose (MTD) of a single dose of the protector 15 to 30 minutes before a single radiation treatment of a size used routinely in palliative management. Study 2 plans to determine the MTD for up to 15 daily doses of the drug over 3 weeks during palliative radiotherapy. Also, the multipe-dose study will establish the MTD before palliative irradiation for fewer than five fractions a week. Study 3 uses the existing single-dose MTD determined in Study 1 as pretreatment 15 to 30 minutes before cyclophosphamide or cis-platinum. Toxic symptoms include emesis, hypotension, hypertension, somnolence, and sneezing. Only one serious episode of hypotension, considered idiosyncratic, and one instance of moderate to severe vomiting have occurred. Forty-one patients have been entered in Study 1 and a dose of 600 mg/m2 has been reached. The next step is to proceed to the planned highest level of 740 mg/m2. Of five patients in the multiple-dose study, one has been given, without toxicity, WR2721 at the level of 100 mg/m2 for 15 fractions over 3 weeks. Fourteen patients are accessed to the alkylating agent study. Using protector doses of 450 mg/m2, a cyclophosphamide level of 1500 mg/m2 has been accomplished. However, two of three patients who received 450 mg/m2 of WR2721 before 120 mg/m2 of cis-platinum have shown moderate elevation of the serum creatinine, both of which returned to normal.

Phase I trials of WR2721 in combination with radiation therapy and with the alkylating agents cyclophosphamide and cis-platinum

International Nuclear Information System (INIS)

Kligerman, M.M.; Blumberg, A.L.; Glick, J.H.; Nelson, D.F.; Glover, D.; Yuhas, J.M.; Amols, H.I.; Goodman, R.L.

1981-01-01

Three phase I trials of the radioprotector S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721) have accessed 60 patients. Study 1 is devised to determine the maximum tolerated dose (MTD) of a single dose of the protector 15 to 30 minutes before a single radiation treatment of a size used routinely in palliative management. Study 2 plans to determine the MTD for up to 15 daily doses of the drug over 3 weeks during palliative radiotherapy. Also, the multipe-dose study will establish the MTD before palliative irradiation for fewer than five fractions a week. Study 3 uses the existing single-dose MTD determined in Study 1 as pretreatment 15 to 30 minutes before cyclophosphamide or cis-platinum. Toxic symptoms include emesis, hypotension, hypertension, somnolence, and sneezing. Only one serious episode of hypotension, considered idiosyncratic, and one instance of moderate to severe vomiting have occurred. Forty-one patients have been entered in Study 1 and a dose of 600 mg/m2 has been reached. The next step is to proceed to the planned highest level of 740 mg/m2. Of five patients in the multiple-dose study, one has been given, without toxicity, WR2721 at the level of 100 mg/m2 for 15 fractions over 3 weeks. Fourteen patients are accessed to the alkylating agent study. Using protector doses of 450 mg/m2, a cyclophosphamide level of 1500 mg/m2 has been accomplished. However, two of three patients who received 450 mg/m2 of WR2721 before 120 mg/m2 of cis-platinum have shown moderate elevation of the serum creatinine, both of which returned to normal

LDRD final report on synthesis of shape-and size-controlled platinum and platinum alloy nanostructures on carbon with improved durability.

Energy Technology Data Exchange (ETDEWEB)

Shelnutt, John Allen; Garcia, Robert M.; Song, Yujiang; Moreno, Andres M.; Stanis, Ronald J.

2008-10-01

This project is aimed to gain added durability by supporting ripening-resistant dendritic platinum and/or platinum-based alloy nanostructures on carbon. We have developed a new synthetic approach suitable for directly supporting dendritic nanostructures on VXC-72 carbon black (CB), single-walled carbon nanotubes (SWCNTs), and multi-walled carbon nanotubes (MWCNTs). The key of the synthesis is to creating a unique supporting/confining reaction environment by incorporating carbon within lipid bilayer relying on a hydrophobic-hydrophobic interaction. In order to realize size uniformity control over the supported dendritic nanostructures, a fast photocatalytic seeding method based on tin(IV) porphyrins (SnP) developed at Sandia was applied to the synthesis by using SnP-containing liposomes under tungsten light irradiation. For concept approval, one created dendritic platinum nanostructure supported on CB was fabricated into membrane electrode assemblies (MEAs) for durability examination via potential cycling. It appears that carbon supporting is essentially beneficial to an enhanced durability according to our preliminary results.

Chk1 Inhibitor SCH900776 Effectively Potentiates the Cytotoxic Effects of Platinum-Based Chemotherapeutic Drugs in Human Colon Cancer Cells

Czech Academy of Sciences Publication Activity Database

Herudková, Jarmila; Paruch, K.; Khirsariya, P.; Souček, Karel; Krkoška, Martin; Blanářová, Olga; Sova, P.; Kozubík, Alois; Vaculová, Alena

2017-01-01

Roč. 19, č. 10 (2017), s. 830-841 ISSN 1476-5586 R&D Projects: GA ČR GA15-06650S Institutional support: RVO:68081707 Keywords : dna-damaging agents * in-vitro * replication checkpoint Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemistry and molecular biology Impact factor: 5.006, year: 2016

Chemotherapeutic potential of diazeniumdiolate-based aspirin prodrugs in breast cancer.

Science.gov (United States)

Basudhar, Debashree; Cheng, Robert C; Bharadwaj, Gaurav; Ridnour, Lisa A; Wink, David A; Miranda, Katrina M

2015-06-01

Diazeniumdiolate-based aspirin prodrugs have previously been shown to retain the anti-inflammatory properties of aspirin while protecting against the common side effect of stomach ulceration. Initial analysis of two new prodrugs of aspirin that also release either nitroxyl (HNO) or nitric oxide (NO) demonstrated increased cytotoxicity toward human lung carcinoma cells compared to either aspirin or the parent nitrogen oxide donor. In addition, cytotoxicity was significantly lower in endothelial cells, suggesting cancer-specific sensitivity. To assess the chemotherapeutic potential of these new prodrugs in treatment of breast cancer, we studied their effect both in cultured cells and in a nude mouse model. Both prodrugs reduced growth of breast adenocarcinoma cells more effectively than the parent compounds while not being appreciably cytotoxic in a related nontumorigenic cell line (MCF-10A). The HNO donor also was more cytotoxic than the related NO donor. The basis for the observed specificity was investigated in terms of impact on metabolism, DNA damage and repair, apoptosis, angiogenesis and metastasis. The results suggest a significant pharmacological potential for treatment of breast cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

Platinum boride nanowires: Synthesis and characterization

International Nuclear Information System (INIS)

Ding Zhanhui; Qiu Lixia; Zhang Jian; Yao Bin; Cui Tian; Guan Weiming; Zheng Weitao; Wang Wenquan; Zhao Xudong; Liu Xiaoyang

2012-01-01

Highlights: ► Platinum boride nanowires have been synthesized via the direct current arc discharge method. ► XRD, TEM and SAED indicate that the nanowires are single-crystal PtB. ► Two broad photoluminescence emission peaks at about 586 nm and 626 nm have been observed in the PL spectroscopy of PtB nanowires. - Abstract: Platinum boride (PtB) nanowires have been successfully fabricated with direct current arc discharge method using a milled mixture of platinum (Pt) and boron nitride (BN) powders. X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to characterize the compositions, morphology, and structures of the samples. The results show that PtB nanowires are 30–50 nm thick and 20–30 μm long. TEM and selected area electron diffraction (SAED) patterns identify that the PtB nanowires are single-crystalline in nature. A growth mechanism based on vapor–liquid–solid (VLS) process is proposed for the formation of nanowires.

Study of enteroparasites infection frequency and chemotherapeutic agents used in pediatric patients in a community living in Porto Alegre, RS, Brazil

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Morrone Fernanda B.

2004-01-01

Full Text Available Parasitic infections caused by intestinal protozoan and helminths affect more than two billion people worldwide and chemotherapy is the most commonly used therapeutic procedure. Considering the problems created by parasitic infections and the incorrect use of drugs, the aim of this work was to detect the frequency of enteroparasites infection and to estimate the use of chemotherapeutic agents in children living in the periphery of the city of Porto Alegre, RS, Brazil. Ninety-six preschool age children, who had parasitological exams and who used antiparasitic drugs, were analyzed. The efficacy of treatment was evaluated by stool examination repeated six months after treatment. The same diagnostic test was used to evaluate parasitological cure, which was defined as absence of eggs and cysts in the stool. From these children, 79 (82.3% were contaminated by some species of parasite, the most prevalent were Ascaris lumbricoides, Trichuris trichiura and Giardia lamblia. The most commonly used drugs were mebendazole (86% of prescriptions and metronidazole (30.3%. The cure rate in the 79 children, examined 6 months after treatment, was 65.3% for A. lumbricoides and 66.1% for T. trichiura. This study suggests that a continuous education program regarding the prevention and treatment of parasitic infections is an essential tool for their eradication.

SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

Science.gov (United States)

Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

2013-01-01

Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial for an organism's favorable response to alkylating agents. Furthermore, an individual's response to alkylating agents can vary considerably from tissue to tissue and from person to person, pointing to genetic and epigenetic mechanisms that modulate alkylating agent toxicity. PMID:22237395

Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats.

Science.gov (United States)

Medhat, Amina; Mansour, Somaya; El-Sonbaty, Sawsan; Kandil, Eman; Mahmoud, Mustafa

2017-07-01

This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.

Increased sensitivity of p53-deficient cells to anticancer agents due to loss of Pms2

Science.gov (United States)

Fedier, A; Ruefenacht, U B; Schwarz, V A; Haller, U; Fink, D

2002-01-01

A large fraction of human tumours carries mutations in the p53 gene. p53 plays a central role in controlling cell cycle checkpoint regulation, DNA repair, transcription, and apoptosis upon genotoxic stress. Lack of p53 function impairs these cellular processes, and this may be the basis of resistance to chemotherapeutic regimens. By virtue of the involvement of DNA mismatch repair in modulating cytotoxic pathways in response to DNA damaging agents, we investigated the effects of loss of Pms2 on the sensitivity to a panel of widely used anticancer agents in E1A/Ha-Ras-transformed p53-null mouse fibroblasts either proficient or deficient in Pms2. We report that lack of the Pms2 gene is associated with an increased sensitivity, ranging from 2–6-fold, to some types of anticancer agents including the topoisomerase II poisons doxorubicin, etoposide and mitoxantrone, the platinum compounds cisplatin and oxaliplatin, the taxanes docetaxel and paclitaxel, and the antimetabolite gemcitabine. In contrast, no change in sensitivity was found after treatment with 5-fluorouracil. Cell cycle analysis revealed that both, Pms2-deficient and -proficient cells, retain the ability to arrest at the G2/M upon cisplatin treatment. The data indicate that the concomitant loss of Pms2 function chemosensitises p53-deficient cells to some types of anticancer agents, that Pms2 positively modulates cell survival by mechanisms independent of p53, and that increased cytotoxicity is paralleled by increased apoptosis. Tumour-targeted functional inhibition of Pms2 may be a valuable strategy for increasing the efficacy of anticancer agents in the treatment of p53-mutant cancers. British Journal of Cancer (2002) 87, 1027–1033. doi:10.1038/sj.bjc.6600599 www.bjcancer.com © 2002 Cancer Research UK PMID:12434296

Characterization of Platinum Electrodes and In-situ Cell Confluency Measurement Based on Current Changes of Cell-Electrodes

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Chin Fhong SOON

2015-04-01

Full Text Available This study aimed at the development of a biosensor to examine the growth confluency of human derived keratinocytes (HaCaT cell lines in-situ. The biosensor consists of a sputter- coated glass substrate with platinum patterns. Cells were grown on the conductive substrates and the confluency of the cells were monitored in-situ based on the conductivity changes of the substrates. Characterization of the cell proliferation and confluency were interrogated using electrical cell-substrate impedance sensing (ECIS techniques and current change of cells using a pico-ammeter. The investigation was followed by the electrical characterization of the platinum electrode (PE using a two probe I-V measurement system. The surface morphology of platinum electrodes were studied using an atomic force microscopy (AFM and the HaCaT cell morphology was studied using Field-Emission Scanning Electron Microscopy (FE-SEM. The microscopy results showed that the cells coupled and proliferated on the platinum electrodes. For monitoring the conductivity and impedance changes of the cell-electrode in-situ, the cover of a Petri dish was inserted with pogo pins to be in contact with the platinum electrodes. The impedance was sampled using the ECIS technique at a twenty-four hour interval. In our findings, the cell proliferation rate can be measured by observing the changes in capacitance or impedance measured at low ac frequencies ranged from 10 - 1 kHz. In good agreement, the current measured at micro-ampere range by the biosensor decreased as the cell coverage area increased over the time. Thus, the percent of cell confluence was shown inversely proportional to the current changes.

Elaboration, physical and electrochemical characterizations of CO tolerant PEMFC anode materials. Study of platinum-molybdenum and platinum-tungsten alloys and composites; Elaborations et caracterisations electrochimiques et physiques de materiaux d'anode de PEMFC peu sensibles a l'empoisonnement par CO: etude d'alliages et de composites a base de platine-molybdene et de platine-tungstene

Energy Technology Data Exchange (ETDEWEB)

Peyrelade, E.

2005-06-15

PEMFC development is hindered by the CO poisoning ability of the anode platinum catalyst. It has been previously shown that the oxidation potential of carbon monoxide adsorbed on the platinum atoms can be lowered using specific Pt based catalysts, either metallic alloys or composites. The objective is then to realize a catalyst for which the CO oxidation is compatible with the working potential of a PEMFC anode. In our approach, to enhance the CO tolerance of platinum based catalyst supported on carbon, we studied platinum-tungsten and platinum-molybdenum alloys and platinum-metal oxide materials (Pt-WO{sub x} and Pt-MoO{sub x}). The platinum based alloys demonstrate a small effect of the second metal towards the oxidation of carbon monoxide. The platinum composites show a better tolerance to carbon monoxide. Electrochemical studies on both Pt-MoO{sub x} and Pt-WO{sub x} demonstrate the ability of the metal-oxides to promote the ability of Pt to oxidize CO at low potentials. However, chrono-amperometric tests reveal a bigger influence of the tungsten oxide. Complex chemistry reactions on the molybdenum oxide surface make it more difficult to observe. (author)

A phototactic micromotor based on platinum nanoparticle decorated carbon nitride.

Science.gov (United States)

Ye, Zhenrong; Sun, Yunyu; Zhang, Hui; Song, Bo; Dong, Bin

2017-11-30

In this paper, we report a unique phototactic (both positive and negative) micromotor based on platinum nanoparticle decorated carbon nitride. The phototaxis relies on the self-diffusiophoretic mechanism and different surface modifications. The micromotor reported in the current study does not require the addition of any external fuels and shows versatile motion behaviour, i.e. start, stop, directional and programmable motion, which is controlled by light. In addition, since the actuation of the precipitated micromotors at the bottom of a solution using light results in the opacity changes from transparent to translucent, we anticipate that the current micromotor may have potential application in the field of smart windows.

OFFGEL isoelectric focusing and polyacrylamide gel electrophoresis separation of platinum-binding proteins.

Science.gov (United States)

Mena, Ma Luz; Moreno-Gordaliza, Estefanía; Moraleja, Irene; Cañas, Benito; Gómez-Gómez, Ma Milagros

2011-03-04

In this work a 2D electrophoretic separation procedure able to maintain the integrity of platinum-protein bonds has been developed. The method is based on the use of sequential OFFGEL isoelectric focussing (IEF) and PAGE. A systematic study of the reagents used for PAGE, for OFFGEL-IEF separation, and post-separation treatment of gels (such as enzymatic digestion and sample preparation for MS analysis) was tackled regarding their suitability for the identification of platinum binding proteins using standard proteins incubated with cisplatin. The distribution of platinum in high and low molecular weight fractions (separated by cut-off filters) was determined by ICP-MS, which allows evaluating platinum-protein bond stability under the conditions studied. SDS-PAGE in the absence of β-mercaptoethanol or dithiotreitol preserved the platinum-protein bonds. In addition, neither the influence of the electric field during the electrophoretic separation, nor the processes of fixing, staining and destaining of proteins in the gel did result in the loss of platinum from platinum binding proteins. SDS-PAGE under non-reducing conditions provides separation of platinum-binding proteins in very narrow bands with quantitative recoveries. Different amounts of platinum-bound proteins covering the range 0.3-2.0 μg were separated and mineralised for platinum determination, showing good platinum linearity. Limits of detection for a mixture of five standard proteins incubated with cisplatin were between the range of 2.4 and 13.9 pg of platinum, which were satisfactory for their application to biological samples. Regarding OFFGEL-IEF, a denaturing solution without thiourea and without dithiotreitol is recommended. The suitability of the OFFGEL-IEF for the separation of platinum binding proteins of a kidney cytosol was demonstrated. Copyright © 2011 Elsevier B.V. All rights reserved.

Cost-effectiveness of adding cetuximab to platinum-based chemotherapy for first-line treatment of recurrent or metastatic head and neck cancer.

Directory of Open Access Journals (Sweden)

Malek B Hannouf

Full Text Available To assess the cost effectiveness of adding cetuximab to platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC from the perspective of the Canadian public healthcare system.We developed a Markov state transition model to project the lifetime clinical and economic consequences of recurrent or metastatic HNSCC. Transition probabilities were derived from a phase III trial of cetuximab in patients with recurrent or metastatic HNSCC. Cost estimates were obtained from London Health Sciences Centre and the Ontario Case Costing Initiative, and expressed in 2011 CAD. A three year time horizon was used. Future costs and health benefits were discounted at 5%.In the base case, cetuximab plus platinum-based chemotherapy compared to platinum-based chemotherapy alone led to an increase of 0.093 QALY and an increase in cost of $36,000 per person, resulting in an incremental cost effectiveness ratio (ICER of $386,000 per QALY gained. The cost effectiveness ratio was most sensitive to the cost per mg of cetuximab and the absolute risk of progression among patients receiving cetuximab.The addition of cetuximab to standard platinum-based chemotherapy in first-line treatment of patients with recurrent or metastatic HNSCC has an ICER that exceeds $100,000 per QALY gained. Cetuximab can only be economically attractive in this patient population if the cost of cetuximab is substantially reduced or if future research can identify predictive markers to select patients most likely to benefit from the addition of cetuximab to chemotherapy.

Novel non-platinum metal catalyst material

DEFF Research Database (Denmark)

2014-01-01

The present invention relates to a novel non-platinum metal catalyst material for use in low temperature fuel cells and electrolysers and to fuel cells and electrolysers comprising the novel non-platinum metal catalyst material. The present invention also relates to a novel method for synthesizing...... the novel non-platinum metal catalyst material....

Photocatalytically active colloidal platinum-decorated cadmium sulphide nanorods for hydrogen production; Photokatalytisch Aktive Kolloidale Platindekorierte Cadmiumsulfidnanostaebchen zur Wasserstoffproduktion

Energy Technology Data Exchange (ETDEWEB)

Berr, Maximilian Josef

2012-12-07

This is the first study to have been successful in producing hydrogen by means of photocatalytically active colloidal semiconductor particles. Specifically, colloidal platinum-decorated cadmium sulphide nanorods were used to reduce water to hydrogen. Oxidation of water to oxygen was substituted by addition of a reducing agent (hole collector), e.g. sulphite, which itself is oxidised to sulphate by the photohole. During photochemical platinum decoration it was discovered that in addition to the expected platinum nanoparticles there had also formed platinum clusters in the subnanometer range. In spite of the small quantity of platinum deposited on the nanorods these clusters showed the same quantum efficiency as the intended product. [German] In dieser Arbeit wurde erstmals mit kolloidalen Halbleiternanopartikeln photokatalytische Wasserstoffproduktion erzielt. Im Detail wurde Wasser mit kolloidalen, platindekorierten Cadmiumsulfidnanostaebchen zu Wasserstoff reduziert. Die Oxidation des Wasser zu Sauerstoff wurde durch Zugabe eines Reduktionsmittels (Lochfaenger) substituiert, z.B. Sulfit, das durch das Photoloch zu Sulfat reduziert wird. Bei der photochemischen Platindekoration wurden neben den erwarteten Platinnanopartikeln mit 4 - 5 nm Durchmesser auch Subnanometer grosse Platincluster entdeckt, die trotz der geringeren Menge an deponierten Platin auf den Nanostaebchen die gleiche Quanteneffizienz demonstrieren.

S-1 monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck after progression on platinum-based chemotherapy

International Nuclear Information System (INIS)

Yokota, Tomoya; Onozawa, Yusuke; Boku, Narikazu

2011-01-01

Platinum compounds play pivotal roles in treatment for squamous cell carcinoma of the head and neck. The objective was to evaluate the efficacy of S-1 monotherapy in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We retrospectively analyzed 39 consecutive patients with recurrent or metastatic squamous cell carcinoma of the head and neck who received S-1 monotherapy after failure of platinum-based chemotherapy or chemoradiotherapy at the Shizuoka Cancer Center between August 2003 and October 2010. S-1 was given orally twice daily (80 mg/m 2 /day) for 28 days followed by a 14-day rest. The median follow-up period in survivors was 31.5 months. Among 38 patients with measurable lesions, 9 (24%) showed partial response and 15 (39%) showed stable disease. The median progression-free survival was 4.9 months and the median overall survival was 13.2 months. The median progression-free survival for oropharyngeal cancer (n=7) was significantly longer than for other cancers (n=32) (14.9 vs. 4.7 months, P=0.035). The response rate in patients with a recurrence-free interval since the last platinum administration >6.0 months was significantly better than with a recurrence-free interval 6.0 months also showed a significantly better progression-free survival (6.0 vs. 2.6 months, P=0.045). The frequency of Grade 3/4 toxicities was less than 10%. S-1 monotherapy shows promising signs of efficacy and tolerability in patients with recurrent or metastatic squamous cell carcinoma of the head and neck after failure of platinum-based chemotherapy in this retrospective cohort and warrants further investigation in this population. (author)

Cisplatin and derivatives with radiation therapy: for what clinical use?

International Nuclear Information System (INIS)

Durdux, C.

2004-01-01

Since its discovery by Rosenberg in 1965, cisplatin and its derivatives have appeared as the most important chemotherapeutic agents, particularly for their radiosensitizing properties and their clinical use with radiation. In spite of numerous preclinical and clinical studies, optimal schedules of platin and radiotherapy combination have to be defined. The first part of this overview will describe biological mechanisms of interaction between radiation therapy and platinum derivatives. The second part will report the major clinical impact of their association. (author)

A comparison of DNA binding profiles of dinuclear platinum compounds with polyamine linkers and the trinuclear platinum phase II clinical agent BBR3464

Czech Academy of Sciences Publication Activity Database

McGregor, T. D.; Hegmans, A.; Kašpárková, Jana; Neplechová, Kamila; Nováková, Olga; Peňázová, Hana; Vrána, Oldřich; Brabec, Viktor; Farrel, N.

2002-01-01

Roč. 7, 4/5 (2002), s. 397-404 ISSN 0949-8257 R&D Projects: GA ČR GA305/99/0695; GA ČR GA301/00/0556; GA ČR GA301/98/P231; GA AV ČR IAA5004101; GA AV ČR IAA7004805 Institutional research plan: CEZ:AV0Z5004920 Keywords : unwinding * dinuclear platinum * hydrogen bonding Subject RIV: BO - Biophysics Impact factor: 3.911, year: 2002

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients.

Science.gov (United States)

Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-10-06

Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression.

A phase 1/2 study combining gemcitabine, Pegintron and p53 SLP vaccine in patients with platinum-resistant ovarian cancer

NARCIS (Netherlands)

Dijkgraaf, Eveline M.; Santegoets, Saskia J. A. M.; Reyners, An K. L.; Goedemans, Renske; Nijman, Hans W.; van Poelgeest, Mariette I. E.; van Erkel, Arien R.; Smit, Vincent T. H. B. M.; Daemen, Toos A. H. H.; van der Hoeven, Jacobus J. M.; Melief, Cornelis J. M.; Welters, Marij J. P.; Kroep, Judith R.; van der Burg, Sjoerd H.

2015-01-01

Purpose: Preclinical tumor models show that chemotherapy has immune modulatory properties which can be exploited in the context of immunotherapy. The purpose of this study was to determine the feasibility and immunogenicity of combinations of such an immunomodulatory chemotherapeutic agent with

Real-world hospital costs for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer in Chinese patients: a retrospective cohort study

Directory of Open Access Journals (Sweden)

Chen JH

2016-04-01

Full Text Available Jianhua Chen,1 Shengqi Wu,2 Chenping Hu,3 Yicheng Yang,4 Narayan Rajan,5 Yun Chen,4 Canjuan Yang,6 Jianfeng Li,6 Wendong Chen7 1Department of Medical Oncology, 2Department of Research and Education, Hunan Province Tumor Hospital, 3Department of Respiratory, Xiangya Hospital, Central South University, Changsha, Hunan, 4Lilly Suzhou Pharmaceutical Co., Ltd. Shanghai Branch, Shanghai, People's Republic of China; 5Global Health Outcomes Research, Eli Lilly and Co, Indianapolis, IN, USA; 6Division of Health Outcome Research, Normin Health Changsha Representative Office, Changsha, Hunan, People's Republic of China; 7Normin Health, Toronto, ON, Canada Objective: The objective of this study was to compare hospital costs per treatment cycle (HCTC for nonchemotherapy drugs and nondrug care associated with platinum-based doublets in the first-line setting for advanced nonsquamous non-small-cell lung cancer (AdvNS-NSCLC in Chinese patients. Methods: Patients receiving platinum-based doublets in the first-line setting for AdvNS-NSCLC from 2010 to 2012 in two Chinese tertiary hospitals were identified to create the retrospective study cohort. Propensity score methods were used to create matched treatment groups for head-to-head comparisons on HCTC between pemetrexed–platinum and other platinum-based doublets. Multiple linear regression analyses were performed to rank studied platinum-based doublets for their associations with the log10 scale of HCTC for nonchemotherapy drugs and nondrug care. Results: Propensity score methods created matched treatment groups for pemetrexed–platinum versus docetaxel–platinum (61 pairs, paclitaxel–platinum (39 pairs, gemcitabine–platinum (93 pairs, and vinorelbine–platinum (73 pairs, respectively. Even though the log10 scale of HCTC for nonchemotherapy drugs and nondrug care associated with pemetrexed–platinum was ranked lowest in all patients (coefficient –0.174, P=0.015, which included patients experiencing

Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

Science.gov (United States)

Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

2005-11-15

One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

Novel platinum black electroplating technique improving mechanical stability.

Science.gov (United States)

Kim, Raeyoung; Nam, Yoonkey

2013-01-01

Platinum black microelectrodes are widely used as an effective neural signal recording sensor. The simple fabrication process, high quality signal recording and proper biocompatibility are the main advantages of platinum black microelectrodes. When microelectrodes are exposed to actual biological system, various physical stimuli are applied. However, the porous structure of platinum black is vulnerable to external stimuli and destroyed easily. The impedance level of the microelectrode increases when the microelectrodes are damaged resulting in decreased recording performance. In this study, we developed mechanically stable platinum black microelectrodes by adding polydopamine. The polydopamine layer was added between the platinum black structures by electrodeposition method. The initial impedance level of platinum black only microelectrodes and polydopamine added microelectrodes were similar but after applying ultrasonication the impedance value dramatically increased for platinum black only microelectrodes, whereas polydopamine added microelectrodes showed little increase which were nearly retained initial values. Polydopamine added platinum black microelectrodes are expected to extend the availability as neural sensors.

Sensitivity to TOP2 targeting chemotherapeutics is regulated by Oct1 and FILIP1L.

Directory of Open Access Journals (Sweden)

Huarui Lu

Full Text Available Topoisomerase II (TOP2 targeting drugs like doxorubicin and etoposide are frontline chemotherapeutics for a wide variety of solid and hematological malignancies, including breast and ovarian adenocarcinomas, lung cancers, soft tissue sarcomas, leukemias and lymphomas. These agents cause a block in DNA replication leading to a pronounced DNA damage response and initiation of apoptotic programs. Resistance to these agents is common, however, and elucidation of the mechanisms causing resistance to therapy could shed light on strategies to reduce the frequency of ineffective treatments. To explore these mechanisms, we utilized an unbiased shRNA screen to identify genes that regulate cell death in response to doxorubicin treatment. We identified the Filamin A interacting protein 1-like (FILIP1L gene as a crucial mediator of apoptosis triggered by doxorubicin. FILIP1L shares significant similarity with bacterial SbcC, an ATPase involved in DNA repair. FILIP1L was originally described as DOC1, or "down-regulated in ovarian cancer" and has since been shown to be downregulated in a wide variety of human tumors. FILIP1L levels increase markedly through transcriptional mechanisms following treatment with doxorubicin and other TOP2 poisons, including etoposide and mitoxantrone, but not by the TOP2 catalytic inhibitors merbarone or dexrazoxane (ICRF187, or by UV irradiation. This induction requires the action of the OCT1 transcription factor, which relocalizes to the FILIP1L promoter and facilitates its expression following doxorubicin treatment. Our findings suggest that the FILIP1L expression status in tumors may influence the response to anti-TOP2 chemotherapeutics.

Six versus fewer planned cycles of first-line platinum-based chemotherapy for non-small-cell lung cancer

DEFF Research Database (Denmark)

Rossi, Antonio; Chiodini, Paolo; Sun, Jong-Mu

2014-01-01

BACKGROUND: Platinum-based chemotherapy is the standard first-line treatment for patients with advanced non-small-cell lung cancer. However, the optimum number of treatment cycles remains controversial. Therefore, we did a systematic review and meta-analysis of individual patient data to compare ...

Chemotherapeutic Drugs and Mitochondrial Dysfunction: Focus on Doxorubicin, Trastuzumab, and Sunitinib

Directory of Open Access Journals (Sweden)

Stefania Gorini

2018-01-01

Full Text Available Many cancer therapies produce toxic side effects whose molecular mechanisms await full elucidation. The most feared and studied side effect of chemotherapeutic drugs is cardiotoxicity. Also, skeletal muscle physiology impairment has been recorded after many chemotherapeutical treatments. However, only doxorubicin has been extensively studied for its side effects on skeletal muscle. Chemotherapeutic-induced adverse side effects are, in many cases, mediated by mitochondrial damage. In particular, trastuzumab and sunitinib toxicity is mainly associated with mitochondria impairment and is mostly reversible. Vice versa, doxorubicin-induced toxicity not only includes mitochondria damage but can also lead to a more robust and extensive cell injury which is often irreversible and lethal. Drugs interfering with mitochondrial functionality determine the depletion of ATP reservoirs and lead to subsequent reversible contractile dysfunction. Mitochondrial damage includes the impairment of the respiratory chain and the loss of mitochondrial membrane potential with subsequent disruption of cellular energetic. In a context of increased stress, AMPK has a key role in maintaining energy homeostasis, and inhibition of the AMPK pathway is one of the proposed mechanisms possibly mediating mitochondrial toxicity due to chemotherapeutics. Therapies targeting and protecting cell metabolism and energy management might be useful tools in protecting muscular tissues against the toxicity induced by chemotherapeutic drugs.

Investigation of mechanical and structural characteristics of platinum and palladium at high temperatures

Energy Technology Data Exchange (ETDEWEB)

Trumie, B. T.; Gomidzelovie, L.; Marjanovic, S. R.; Krstic, V. R.

2015-03-30

In order to broaden future application of products based on platinum and palladium a comparative analysis of their high-temperature mechanical properties was performed. Platinum and palladium are of great importance and are widely used in chemical industry, electronics, for making laboratory dishes, to name a few. Mechanical properties of pure metals, such as: tensile strength, creep rate and rupture time were investigated using universal testing machine for tensile testing of materials. Microstructure of samples was investigated by optical microscopy. Based on obtained results it can be concluded that the platinum, compared to palladium, is superior for high-temperature applications. (Author)

Investigation of mechanical and structural characteristics of platinum and palladium at high temperatures

International Nuclear Information System (INIS)

Trumie, B. T.; Gomidzelovie, L.; Marjanovic, S. R.; Krstic, V. R.

2015-01-01

In order to broaden future application of products based on platinum and palladium a comparative analysis of their high-temperature mechanical properties was performed. Platinum and palladium are of great importance and are widely used in chemical industry, electronics, for making laboratory dishes, to name a few. Mechanical properties of pure metals, such as: tensile strength, creep rate and rupture time were investigated using universal testing machine for tensile testing of materials. Microstructure of samples was investigated by optical microscopy. Based on obtained results it can be concluded that the platinum, compared to palladium, is superior for high-temperature applications. (Author)

Electrical Discharge Platinum Machining Optimization Using Stefan Problem Solutions

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I. B. Stavitskiy

2015-01-01

Full Text Available The article presents the theoretical study results of platinum workability by electrical discharge machining (EDM, based on the solution of the thermal problem of moving the boundary of material change phase, i.e. Stefan problem. The problem solution enables defining the surface melt penetration of the material under the heat flow proceeding from the time of its action and the physical properties of the processed material. To determine the rational EDM operating conditions of platinum the article suggests relating its workability with machinability of materials, for which the rational EDM operating conditions are, currently, defined. It is shown that at low densities of the heat flow corresponding to the finishing EDM operating conditions, the processing conditions used for steel 45 are appropriate for platinum machining; with EDM at higher heat flow densities (e.g. 50 GW / m2 for this purpose copper processing conditions are used; at the high heat flow densities corresponding to heavy roughing EDM it is reasonable to use tungsten processing conditions. The article also represents how the minimum width of the current pulses, at which platinum starts melting and, accordingly, the EDM process becomes possible, depends on the heat flow density. It is shown that the processing of platinum is expedient at a pulse width corresponding to the values, called the effective pulse width. Exceeding these values does not lead to a substantial increase in removal of material per pulse, but considerably reduces the maximum repetition rate and therefore, the EDM capacity. The paper shows the effective pulse width versus the heat flow density. It also presents the dependences of the maximum platinum surface melt penetration and the corresponding pulse width on the heat flow density. Results obtained using solutions of the Stephen heat problem can be used to optimize EDM operating conditions of platinum machining.

Pathogenesis-based treatment of chemotherapy-induced nausea and vomiting--two new agents.

Science.gov (United States)

Navari, Rudolph M

2003-01-01

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors (female gender, younger age, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Although the 5-HT3 receptor antagonists, dexamethasone, and metoclopramide have been used to prevent delayed CINV, only dexamethasone appears to have much efficacy with acceptable toxicity. Recent studies have introduced two new agents, palonosetron and aprepitant, for the prevention of both acute and delayed CINV. Palonosetron is a new 5-HT3 receptor antagonist with a longer half life and a higher binding affinity than older 5-HT3 receptor antagonists. It improves the complete response rate (no emesis, no need for rescue) of acute and delayed CINV in patients receiving moderately emetogenic chemotherapy compared to the older 5-HT3 receptor antagonists. The other agent, aprepitant, is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. Aprepitant also improves the complete response of delayed CINV when compared to placebo and when used in combination with dexamethasone compared to dexamethasone alone. Acute and delayed nausea may also be improved by aprepitant when used in combination with a 5-HT3 and dexamethasone prechemotherapy or with daily dosing for 3-5 days following chemotherapy. Based on these studies, new guidelines for the prevention of CINV are proposed. Future studies may consider the use of

A review on the chemotherapeutic potential of fisetin: In vitro evidences.

Science.gov (United States)

Sundarraj, Kiruthika; Raghunath, Azhwar; Perumal, Ekambaram

2018-01-01

During the past five decades, cancer cell lines are being successfully used as an in vitro model to discover the anti-cancer potential of plant secondary metabolites. Fisetin - the most popular polyphenol from fruits and vegetables, exhibits a repertoire of promising pharmacological features. Such versatile properties make fisetin an excellent anticancer agent and its efficacy as a chemotherapeutic agent against tumor heterogeneity from in vitro studies are encouraging. Fisetin is like a Pandora's box, as more research studies are being carried out, it reveals its new molecules within the cancer cells as therapeutic targets. These molecular targets orchestrate processes such as apoptosis, autophagic cell death, cell cycle, invasion, metastasis and angiogenesis in cancer cells. Besides apoptotic elicitation, fisetin's ability to induce autophagic cell death in cancer cells has been reported. This review examines the various molecular mechanisms of action elicited by fisetin leading to apoptosis and autophagic cell death as evidenced from cancer cell lines. In addition, the increased bioavailability and sustained release of fisetin improved through conjugation and enhanced effect of fisetin through synergism on various cancers are also highlighted. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Development of inductively coupled plasma atomic emission spectrometry for palladium and Rhodium determination in platinum-based alloy

International Nuclear Information System (INIS)

Kovacevic, R.; Todorovic, M.; Manojlovic, D.; Mutic, J.

2008-01-01

Inductively coupled plasma atomic emission spectroscopy with internal standardization was applied for the analysis of an in-house reference platinum alloy containing palladium and rhodium (approximately 5% by weight). In order to compensate for variations in signal recovery due to matrix interferences, and therefore to improve the precision, platinum. the major component, was chosen as an internal standard. Quantitative analysis was based on calibration using a set of matrix-matched calibration standards with and without employing the internal standard. These results were compared with those obtained by X-ray fluorescence spectroscopy. The results for both techniques were in a good agreement, although the precision was slightly better in the inductively coupled plasma atomic emission spectroscopy technique, with or without the internal standard

Stability of Porous Platinum Nanoparticles: Combined In Situ TEM and Theoretical Study

DEFF Research Database (Denmark)

Chang, Shery L. Y.; Barnard, Amanda S.; Dwyer, Christian

2012-01-01

Porous platinum nanoparticles provide a route for the development of catalysts that use less platinum without sacrificing catalytic performance. Here, we examine porous platinum nanoparticles using a combination of in situ transmission electron microscopy and calculations based on a first-principles......-parametrized thermodynamic model. Our experimental observations show that the initially irregular morphologies of the as-sythesized porous nanoparticles undergo changes at high temperatures to morphologies having faceted external surfaces with voids present in the interior of the particles. The increasing size of stable...

The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma.

Science.gov (United States)

Ak, Guntulu; Metintas, Selma; Akarsu, Muhittin; Metintas, Muzaffer

2015-07-09

.470). The treatment was generally well tolerated, and the side effects were similar in both groups. The study indicates that platinum-based gemcitabine is effective and a safe schema in malignant pleural mesothelioma. Further research should include large randomized phase III trials comparing these agents.

EGCG Enhances Cisplatin Sensitivity by Regulating Expression of the Copper and Cisplatin Influx Transporter CTR1 in Ovary Cancer.

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Xuemin Wang

Full Text Available Cisplatin is one of the first-line platinum-based chemotherapeutic agents for treatment of many types of cancer, including ovary cancer. CTR1 (copper transporter 1, a transmembrane solute carrier transporter, has previously been shown to increase the cellular uptake and sensitivity of cisplatin. It is hypothesized that increased CTR1 expression would enhance the sensitivity of cancer cells to cisplatin (cDDP. The present study demonstrates for the first time that (--epigallocatechin-3-gallate (EGCG, a major polyphenol from green tea, can enhance CTR1 mRNA and protein expression in ovarian cancer cells and xenograft mice. EGCG inhibits the rapid degradation of CTR1 induced by cDDP. The combination of EGCG and cDDP increases the accumulation of cDDP and DNA-Pt adducts, and subsequently enhances the sensitivity of ovarian cancer SKOV3 and OVCAR3 cells to the chemotherapeutic agent. In the OVCAR3 ovarian cancer xenograft nude mice model, the combination of the lower concentration of cDDP and EGCG strongly repressed the tumor growth and exhibited protective effect on the nephrotoxicity induced by cisplatin. Overall, these findings uncover a novel chemotherapy mechanism of EGCG as an adjuvant for the treatment of ovarian cancer.

Activation analysis for platinum in gold and metals of the platinum group through 199Au

International Nuclear Information System (INIS)

Foerster, H.

1976-01-01

Platinum was determined in gold and in metals of the platinum group through 199 Au by activation analysis. The matrix was separated at the end of irradiation before the daughter nuclide was formed. Gold was separated by extraction with MIBK from 1

Low platinum catalyst and method of preparation

Energy Technology Data Exchange (ETDEWEB)

Liu, Di-Jia; Chong, Lina

2017-11-21

A low platinum catalyst and method for making same. The catalyst comprises platinum-transition metal bimetallic alloy microcrystallites over a transition metal-nitrogen-carbon composite. A method of making a catalyst comprises preparation of transition metal organic frameworks, infusion of platinum, thermal treatment, and reduction to form the microcrystallites and composite.

Cytotoxic evaluation upon cis-platinum aminodiacetic acid complexes

International Nuclear Information System (INIS)

Almah binti Awaluddin; Parsons, Peter G.; Lean, Jenny M.; Jacobs, Jeffrey J.

1990-01-01

Cytoxic study of cis-platinum aminodiacetic acid complexes. Three novel platinum complexes have been synthesised and characterised by Awaluddin et. al (1987). This introduces a new area of radiopharmaceuticals based on technician and platinum. Cytotoxic studies were conducted on these complexes using four different types of cell lines. The para amina was found to be highly active against multi-resistant ovarian tumor cells compared to normal cells (fibroblast) and other tumor cells. The chemical structure of para-amina appears to be devoid of any functional group resembling current antitumor drugs except for a distant similarity to metotrexate with respect to the p-aminobenzoic type structure. However cell lines such as Hela and MM 253c-1, which is sensitive to metotrexate, were not sensitive to the para amina. Preliminary studies have shown that cells are blocked in the G phase of the cell cycle, suggesting an antimetabolite effect

Biosensors Based on Urease Adsorbed on Nickel, Platinum, and Gold Conductometric Transducers Modified with Silicalite and Nanozeolites

Science.gov (United States)

Kucherenko, Ivan S.; Soldatkin, Oleksandr O.; Kasap, Berna Ozansoy; Kurç, Burcu Akata; Melnyk, Volodymir G.; Semenycheva, Lyudmila M.; Dzyadevych, Sergei V.; Soldatkin, Alexei P.

This work describes urease-based conductometric biosensors that were created using nontypical method of urease immobilization via adsorption on micro- and nanoporous particles: silicalite and nanocrystalline zeolites Beta (BEA) and L. Conductometric transducers with nickel, gold, and platinum interdigitated electrodes were used. Active regions of the nickel transducers were modified with microparticles using two procedures—spin coating and drop coating. Gold and platinum transducers were modified with silicalite using drop coating since it was more effective. Scanning electron microscopy was used to evaluate effectiveness of these procedures. The procedure of spin coating produced more uniform layers of particles (and biosensors had good reproducibility of preparation), but it was more complicated, drop coating was easier and led to formation of a bulk of particles; thus, biosensors had bigger sensitivity but worse reproducibility of preparation. Urease was immobilized onto transducers modified with particles by physical adsorption. Analytical characteristics of the obtained biosensors for determination of urea (calibration curves, sensitivity, limit of detection, linear concentration range, noise of responses, reproducibility of signal during a day, and operational stability during 3 days) were compared. Biosensors with all three particles deposited by spin coating showed similar characteristics; however, silicalite was a bit more effective. Biosensors based on nickel transducers modified by drop coating had better characteristics in comparison with modification by spin coating (except reproducibility of preparation). Transducers with gold electrodes showed best characteristics while creating biosensors, platinum electrodes were slightly inferior to them, and nickel electrodes were the worst.

The role of support and promoter on the oxidation of sulfur dioxide using platinum based catalysts

DEFF Research Database (Denmark)

Koutsopoulos, Sotiris; Rasmussen, Søren Birk; Eriksen, Kim Michael

2006-01-01

The catalytic oxidation of SO2 to SO3 was studied over platinum based catalysts in the absence and the presence of dopants. The active metal was supported on silica gel or titania (anatase) by impregnation. The activities of the silica supported catalysts were found to follow the order PtRh/SiO2 ...

Microstructural Study on Oxidation Resistance of Nonmodified and Platinum Modified Aluminide Coating

Science.gov (United States)

Zagula-Yavorska, Maryana; Sieniawski, Jan

2014-03-01

Platinum electroplating layers (3 and 7 μm thick) were deposited on the surface of the Inconel 713 LC, CMSX 4, and Inconel 625 Ni-base superalloys. Diffusion treatment at 1050°C for 2 h under argon atmosphere was performed after electroplating. Diffusion treated samples were aluminized according to the low activity CVD process at 1050°C for 8 h. The nonmodified aluminide coatings consist of NiAl phase. Platinum modification let to obtain the (Ni,Pt)Al phase in coatings. The coated samples were subjected to cyclic oxidation testing at 1100°C. It was discovered that increase of the platinum electroplating thickness from 3 to 7 μm provides the improvement of oxidation resistance of aluminide coatings. Increase of the platinum thickness causes decreases in weight change and decreases in parabolic constant during oxidation. The platinum provides the pure Al2O3 oxide formation, slow growth oxide layer, and delay the oxide spalling during heating-cooling thermal cycles.

Platinum recycling in the United States in 1998

Science.gov (United States)

Hilliard, Henry E.

2001-01-01

In the United States, catalytic converters are the major source of secondary platinum for recycling. Other sources of platinum scrap include reforming and chemical process catalysts. The glass industry is a small but significant source of platinum scrap. In North America, it has been estimated that in 1998 more than 20,000 kilograms per year of platinum-group metals from automobile catalysts were available for recycling. In 1998, an estimated 7,690 kilograms of platinum were recycled in the United States. U.S. recycling efficiency was calculated to have been 76 percent in 1998; the recycling rate was estimated at 16 percent.

Effects of chemotherapeutics on organotypic corticostriatal slice cultures identified by a panel of fluorescent and immunohistochemical markers

DEFF Research Database (Denmark)

Nørregaard, Annette; Jensen, Stine Skov; Kolenda, Jesper

2012-01-01

no toxicity was observed. Corresponding immunostaining showed loss of MAP2 and increased expression of GFAP and p25α for cultures exposed to 1,000 nM VCR. Cultures exposed to high concentrations of ACNU and IM disintegrated, leaving no tissue for histology. In conclusion, corticostriatal slice cultures...... specific neuronal and glial degeneration induced by chemotherapeutics in organotypic rat corticostriatal slice cultures. The slice cultures were exposed to the alkylating agents temozolomide (TMZ) and nimustine (ACNU), the tyrosine kinase inhibitor imatinib mesylate (IM) and the microtubule...

Reaction of a chemotherapeutic agent, 6-mercaptopurine, with a direct-acting, electrophilic carcinogen, benzo[a]pyrene-7,8-diol 9,10-epoxide.

Science.gov (United States)

MacLeod, M C; Stewart, E; Daylong, A; Lew, L K; Evans, F E

1991-01-01

The chemotherapeutic agent 6-mercaptopurine (6-MP) has been shown to react covalently with the ultimate carcinogenic metabolite of benzo[a]pyrene, 7-r,8-t-dihydroxy-9-t,10-t-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE), in aqueous solution, forming a single adduct. NMR studies of the HPLC-purified product were consistent with its identification as 10(S)-(6'-mercaptopurinyl)-7,8,9-trihydroxy-7,8,9,10- tetrahydrobenzo[a]pyrene. Reaction kinetics were analyzed by using both HPLC separation of the products formed and a spectrophotometric assay for adduct formation. A simple model in which direct reaction between 6-MP and BPDE takes place without formation of a physical complex was found to adequately predict the dependence of product ratios on 6-MP concentration. Variations in the observed rate constant for this reaction with changes in temperature, pH, and buffer concentration were determined and compared to the effects of these variables on the observed rate constant for BPDE hydrolysis. In each case, the processes were affected quite differently, suggesting that different rate-determining steps are involved. The data suggest that the reaction mechanism involves SN2 attack of the anion of 6-MP, formed by ionization of the sulfhydryl group, on carbon 10 of BPDE, resulting in a trans-9,10 reaction product.

A Meta-Analysis of Platinum Plus Gemcitabine or Vinorelbine for Advanced Non-small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Guanghui GAO

2009-01-01

Full Text Available Background and objective Platinum plus the third-generation agent doublet chemotherapy is the standard regimens and first line chemotherapy for advanced non-small cell lung cancer (NSCLC. The aim of this study is to determine the benefits and harms of platinum plus gemcitabine or vinorelbine for advanced NSCLC. Methods Thedatabases PubMed, CENTRAL, EMBASE and Chinese Biomedical Literature database were retrieved by using the key words "non small cell lung cancer" or "Carcinoma, Non Small Cell Lung" so as to search the studies about the randomized controlled clinical trials (RCT that had compared the gemcitabine plus platinum versus vinorelbine plus platinum for advanced NSCLC. A meta-analysis was conducted. Results Nine randomized controlled trials, with total 2 186 patients,were included. The overall response rate and one-year survival rate of the gemcitabine group were not significantly different from that of vinorelbine regimen (RR=0.91, 95%CI: 0.81-1.03, P =0.15; RR=1.06, 95%CI: 0.96-1.18, P =0.27, respectively. The incidence rate of grade 3-4 netropenia, constipation, phlebitis and grade 1-4 neuropathy were higher in vinorelbine group, just like higher incidence rate of grade 3-4 thrombocytopenia in the gemcitabine group. Conclusion The curative effects of the gemcitabine or vinorelbine plus platinum regimens are similar. The choice of gemcitabine or vinorelbine depends on the toxicity of the drugs and patients' tolerance.

Pilot study on developing a decision support tool for guiding re-administration of chemotherapeutic agent after a serious adverse drug reaction

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Chew Lita

2011-07-01

Full Text Available Abstract Background Currently, there are no standard guidelines for recommending re-administration of a chemotherapeutic drug to a patient after a serious adverse drug reaction (ADR incident. The decision on whether to rechallenge the patient is based on the experience of the clinician and is highly subjective. Thus the aim of this study is to develop a decision support tool to assist clinicians in this decision making process. Methods The inclusion criteria for patients in this study are: (1 had chemotherapy at National Cancer Centre Singapore between 2004 to 2009, (2 suffered from serious ADRs, and (3 were rechallenged. A total of 46 patients fulfilled the inclusion criteria. A genetic algorithm attribute selection method was used to identify clinical predictors for patients' rechallenge status. A Naïve Bayes model was then developed using 35 patients and externally validated using 11 patients. Results Eight patient attributes (age, chemotherapeutic drug, albumin level, red blood cell level, platelet level, abnormal white blood cell level, abnormal alkaline phosphatase level and abnormal alanine aminotransferase level were identified as clinical predictors for rechallenge status of patients. The Naïve Bayes model had an AUC of 0.767 and was found to be useful for assisting clinical decision making after clinicians had identified a group of patients for rechallenge. A platform independent version and an online version of the model is available to facilitate independent validation of the model. Conclusion Due to the limited size of the validation set, a more extensive validation of the model is necessary before it can be adopted for routine clinical use. Once validated, the model can be used to assist clinicians in deciding whether to rechallenge patients by determining if their initial assessment of rechallenge status of patients is accurate.

Irinotecan and oxaliplatin: an overview of the novel chemotherapeutic options for the treatment of advanced colorectal cancer

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I. Grivicich

2001-09-01

Full Text Available Colorectal cancer is one of the most frequent malignancies in humans and an important cause of cancer death. Metastatic colorectal cancer remains incurable with available systemic therapeutic options. The most active cytotoxic drug against this malignancy, the antimetabolite 5-fluorouracil, was developed more than forty years ago, and as a single agent produces responses in only 10 to 15% of patients which in general last less than one year. Efforts to ameliorate these poor results resulted in the 5-fluorouracil/leucovorin combination, which enhances response rates about two-fold, without, however, significantly improving survival rates. The recent emergence of a handful of new 5-fluorouracil analogues and folate antagonists, as well as the topoisomerase I inhibitor irinotecan, and the third-generation platinum compound oxaliplatin, is likely to alter this gloomy scenario. These agents are at least as effective as 5-fluorouracil in patients with advanced colorectal carcinoma, both untreated and previously treated with 5-fluorouracil-based regimens. This has led to the approval of irinotecan as second-line treatment for 5-fluorouracil-refractory disease, while the use of oxaliplatin has been suggested for patients having a defective 5-fluorouracil catabolism. Recently, FDA approved the combination of irinotecan with 5-fluorouracil and leucovorin for first-line treatment of advanced colon cancer. Based on the synergistic preclinical antitumor effects of some of these agents, their meaningful single-agent activity, distinct mechanisms of cytotoxicity and resistance, and only partially overlapping toxicity profiles, effective combination regimens are now being developed, which are likely to lead to a new, more hopeful era for patients suffering from advanced colorectal carcinoma.

Determination of microquantities of silver in platinum by isotope dilution

International Nuclear Information System (INIS)

Yedinakova, V.; Sladkovska, Y.

1980-01-01

A method is described for determining microquantities of silver in platinum. It is based on isotope dilution by means of substoichiometric extraction of dithizonates with carbon tetrachloride. The determination of silver according to this technique is not interfered by zinc or gold in quantities exceeding the silver content by one order of magnitude nor by a great excess of platinum. In the presence of copper the addition of complexon is necessary. (author)

SINGLE AGENT DOCETAXEL AS SECOND- LINE CHEMOTHERAPY FOR PRETREATED PATIENTS WITH RECURRENT NON- SMALL CELL LUNG CANCER

Directory of Open Access Journals (Sweden)

Deyan N. Davidov

2013-04-01

Full Text Available Objective: Single agent Docetaxel is a standard therapy for patients with non- small cell lung cancer after the failure of platinum- containing regimens. The aim of this study was to explore the efficacy and safety of Docetaxel monotherapy as second- line chemotherapy in pretreated patient with inoperable non- small cell lung cancer. Methods: From January 2005 to May 2008 thirty- six consecutive patients with locally advanced or metastatic morphologically proven stage IIIB/ IV non- small cell lung cancer entered the study after failure of previous platinum- based regimens. Treatment schedule consist of Docetaxel 75 mg/m2 administered every three weeks with repetition after 21 days with Dexamethasone premedication. Results: Overall response rate, median time to progression and median survival was 16,6 %, 4,5 months and 5,6 months respectively. The main hematological toxicity was neutropenia. Conclusions: That data suggest that single agent Docetaxel remain reasonable choices for the chemotherapy in pretreated patients with non- small cell lung cancer.

Agent-based modeling and network dynamics

CERN Document Server

Namatame, Akira

2016-01-01

The book integrates agent-based modeling and network science. It is divided into three parts, namely, foundations, primary dynamics on and of social networks, and applications. The book begins with the network origin of agent-based models, known as cellular automata, and introduce a number of classic models, such as Schelling’s segregation model and Axelrod’s spatial game. The essence of the foundation part is the network-based agent-based models in which agents follow network-based decision rules. Under the influence of the substantial progress in network science in late 1990s, these models have been extended from using lattices into using small-world networks, scale-free networks, etc. The book also shows that the modern network science mainly driven by game-theorists and sociophysicists has inspired agent-based social scientists to develop alternative formation algorithms, known as agent-based social networks. The book reviews a number of pioneering and representative models in this family. Upon the gi...

Renal function and urological complications after radical hysterectomy with postoperative radiotherapy and platinum-based chemotherapy for cervical cancer.

Science.gov (United States)

Okadome, Masao; Saito, Toshiaki; Kitade, Shoko; Ariyoshi, Kazuya; Shimamoto, Kumi; Kawano, Hiroyuki; Minami, Kazuhito; Nakamura, Motonobu; Shimokawa, Mototsugu; Okushima, Kazuhiro; Kubo, Yuichiro; Kunitake, Naonobu

2018-02-01

We aimed to clarify renal functional changes long term and serious urological complications in women with cervical cancer who undergo radical hysterectomy followed by pelvic radiotherapy and/or platinum-based chemotherapy to treat the initial disease. Data on 380 women who underwent radical hysterectomy at the National Kyushu Cancer Center from January 1997 to December 2013 were reviewed. Main outcome measures were the estimated glomerular filtration rate (eGFR) and monitored abnormal urological findings. Postoperative eGFR was significantly lower than preoperative eGFR in 179 women with surgery alone and in 201 women with additional pelvic radiotherapy and/or chemotherapy (both P types of univariate analyses for eGFR reduction in women after treatment showed that older age, advanced stage, pelvic radiotherapy, and platinum-based chemotherapy were significant variables on both analyses. Two types of multivariate analyses showed that platinum-based chemotherapy or pelvic radiotherapy were associated with impaired renal function (odds ratio 1.96, 95% confidence interval 1.08-3.54 and odds ratio 2.85, 95% confidence interval 1.12-7.24, for the respective analyses). There was a higher rate of bladder wall thickening in women with pelvic radiotherapy had than those without it (17.4% vs. 2.7%, P chemotherapy and/or postoperative pelvic radiotherapy. Serious and life-threatening urological complications are rare, but surgeons should be aware of the possibility during the long follow-up. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of platinum in biological systems - toxicology and pharmaceutical applications; Wirkungen von Platin in biologischen Systemen - Toxikologie und pharmazeutische Anwendung

Energy Technology Data Exchange (ETDEWEB)

Nachtigall, D [Fraunhofer-Institut fuer Toxikologie und Aerosolforschung, Hannover (Germany)

1998-12-31

The title of this lecture has intentionally been worded rather vaguely with ``biological systems`` to do justice to the fact that there are meanwhile extensive data available on diverse levels of the toxicology and structure-effect relationships of some platinum compounds. These range from epidemiological descriptions over toxicity studies to molecular biological reaction mechanisms. Any discussion on the toxicity of a substance implies that the substance poses a direct or indirect hazard to humans. In the case of platinum and its compounds there are three main categories of exposure: platinum production including workplaces in the platinum processing industries; clinical treatment with antineoplastic platinum-containing agents; and, finally, the environment, where platinum levels are known to be rising since some years. The association between these exposures becomes clear when one considers the platinum pollution caused by automobile catalytic converters, hospital effluents, and by platinum-containing industrial products in the widest sense. [Deutsch] Der Titel des Vortrages ist mit `biologischen Systemen` sehr allgemein gehalten, da ueber die Toxikologie und die Struktur-Wirkungsbeziehungen einiger Platinverbindungen auf den verschiedensten Ebenen umfangreiche Daten vorliegen. Diese reichen von epidemiologischen Beschreibungen ueber Toxizitaetsstudien bis hin zu molekularbiologischen Reaktionsmechanismen. Die Diskussion um die Toxizitaet von Substanzen impliziert immer die direkte oder indirekte Gefaehrdung des Menschen. Im Falle des Platins und seiner Verbindungen existieren drei wesentliche Expositionsbereiche: Die Platingewinnung sowie die Arbeitsplaetze in der Platin verarbeitenden Industrie, die klinische Behandlung mit antineoplastischen Platinwirkstoffen und schliesslich die Umwelt, in der seit einigen Jahren ansteigende Platinkonzentrationen verzeichnet werden. Die Verbindung zwischen diesen Bereichen wird deutlich, wenn man die Platinimmissionen durch

Effects of platinum in biological systems - toxicology and pharmaceutical applications; Wirkungen von Platin in biologischen Systemen - Toxikologie und pharmazeutische Anwendung

Energy Technology Data Exchange (ETDEWEB)

Nachtigall, D. [Fraunhofer-Institut fuer Toxikologie und Aerosolforschung, Hannover (Germany)

1997-12-31

The title of this lecture has intentionally been worded rather vaguely with ``biological systems`` to do justice to the fact that there are meanwhile extensive data available on diverse levels of the toxicology and structure-effect relationships of some platinum compounds. These range from epidemiological descriptions over toxicity studies to molecular biological reaction mechanisms. Any discussion on the toxicity of a substance implies that the substance poses a direct or indirect hazard to humans. In the case of platinum and its compounds there are three main categories of exposure: platinum production including workplaces in the platinum processing industries; clinical treatment with antineoplastic platinum-containing agents; and, finally, the environment, where platinum levels are known to be rising since some years. The association between these exposures becomes clear when one considers the platinum pollution caused by automobile catalytic converters, hospital effluents, and by platinum-containing industrial products in the widest sense. [Deutsch] Der Titel des Vortrages ist mit `biologischen Systemen` sehr allgemein gehalten, da ueber die Toxikologie und die Struktur-Wirkungsbeziehungen einiger Platinverbindungen auf den verschiedensten Ebenen umfangreiche Daten vorliegen. Diese reichen von epidemiologischen Beschreibungen ueber Toxizitaetsstudien bis hin zu molekularbiologischen Reaktionsmechanismen. Die Diskussion um die Toxizitaet von Substanzen impliziert immer die direkte oder indirekte Gefaehrdung des Menschen. Im Falle des Platins und seiner Verbindungen existieren drei wesentliche Expositionsbereiche: Die Platingewinnung sowie die Arbeitsplaetze in der Platin verarbeitenden Industrie, die klinische Behandlung mit antineoplastischen Platinwirkstoffen und schliesslich die Umwelt, in der seit einigen Jahren ansteigende Platinkonzentrationen verzeichnet werden. Die Verbindung zwischen diesen Bereichen wird deutlich, wenn man die Platinimmissionen durch

The effects of thermal-neutron irradiation on platinum and dilute platinum-gold alloys

International Nuclear Information System (INIS)

Piani, C.S.B.

1978-12-01

The effect of varying defect concentrations on the recovery spectrum of thermal-neutron-irradiated pure platinum after isochronal anneals was investigated. The dose-independence of substages I(A), I(B) and I(C), and the dose dependence of substage I(D) and I(E), were observed to be in agreement with electron-irradiated studies. The 120 K substage in pure platinum was shown not to be due to interstitial-interstitial reactions, but could possibly be accounted for in terms of detrapping of interstitials from impurities or intrinsic immobile defects. The 360 K stage was shown to shift and was suppressed with increasing defect concentration. The possible conversion of the crowdion to a dumbbell near 160 K in Stage ll in platinum, as predicted by the two-interstitial model, was investigated by consideration of the initial slopes of the production curves between 80 K and 300 K. A minimum in these slopes was observed near 160 K and could be interpreted as due to the conversion of the highly mobile crowdion to an immobile dumbbell at this temperature. The influence of varying gold concentrations on the recovery spectrum of platinum was investigated in dilute platinum-gold alloys. The characteristics of several additional substages in Stage ll, due to the gold alloying were comparable to the results of electron-irradiation experiments. The observations made with regard to the impurity (gold) dependence of these substages could be interpreted in terms of the concentrations of the interstitials, vacancies and impurities present in the material. The interpretation of these substages was found to be consistent, if the recovery spectrum was investigated as a function of defect concentration [af

Novel 3-(aminomethyl)naphthoquinone mannich base-platinum(IV) complexes: synthesis, characterization, electrochemical and cytotoxic studies

International Nuclear Information System (INIS)

Silva, Gustavo B. da; Neves, Amanda P.; Vargas, Maria D.; Alves, Wagner A.; Marinho-Filho, Jose D.B.; Pessoa, Claudia; Moraes, Manoel O.; Costa-Lotufo, Leticia V.

2013-01-01

Three novel platinum(IV) complexes cis,cis,trans-[Pt(HL1-3)Cl 2 (OH) 2 ] 1b-3b(HL = 2-hydroxy-3-[(R 1 -amino)(pyridin-2-yl)methyl]-1,4-naphthoquinone, R 1 = n-butyl, HL1; n-heptyl, HL2 and n-decyl, HL3) have been obtained from the oxidation of the respective precursors cis-[Pt(HL1-3)Cl 2 ] 1a-3a. Cyclic voltammetry studies of 1b-3b in MeCN showed the quasi reversible naphthoquinonate (NQO - , i.e., L - ) redox process and irreversible process attributed to the reduction of the Pt 4+ /Pt 2+ pair, at potentials about 400 mV less negative than for the cisplatin precursor cis,cis,trans-[Pt(NH 3 ) 2 Cl 2 (OH) 2 ]. Hydrogen bond interaction between the naphthoquinone 2-hydroxyl group and an axially coordinated hydroxide ligand in 1b-3b has been proposed to favor the Pt 4+ /Pt 2+ reduction. The cytotoxicity studies against four human cancer cell lines have shown that in general the platinum(IV) and platinum(II)derivatives exhibit the same cytotoxic profile and are all more active than cisplatin. The lowest in vitro IC 50 values have been observed for 2b-3b, which bear ligands with the largest R 1 groups (HL2-HL3) being the most lipophilic. Furthermore similar IC 50 values for platinum(II) and platinum(IV) complexes of the same ligands have been associated with rapid in vitro reduction of the latter complexes to afford 1a-3a. (author)

Role of Reactive Oxygen Species and Nitric Oxide in Mediating Chemotherapeutic Drug Induced Bystander Response in Human Cancer Cells Exposed In-Vitro

Science.gov (United States)

Chinnadurai, Mani; Rao, Bhavna S; Deepika, Ramasamy; Paul, Solomon F.D.; Venkatachalam, Perumal

2012-01-01

Background The intention of cancer chemotherapy is to control the growth of cancer cells using chemical agents. However, the occurrence of second malignancies has raised concerns, leading to re-evaluation of the current strategy in use for chemotherapeutic agents. Although the mechanisms involved in second malignancy remain ambiguous, therapeutic-agent-induced non-DNA targeted effects like bystander response and genomic instability cannot be eliminated completely. Hence, Bleomycin (BLM) and Neocarzinostatin (NCS), chemotherapeutic drugs with a mode of action similar to ionizing radiation, were used to study the mechanism of bystander response in human cancer cells (A549, CCRF-CEM and HL-60) by employing co-culture methodology. Methods Bystander effect was quantified using micronucleus (MN) assay and in-situ immunofluorescence(γH2AX assay).The role of reactive oxygen species (ROS) and nitric oxide (NO) in mediating the bystander response was explored by pre-treating bystander cells with dimethylsulphoxide (DMSO) and C-PTIO respectively. Results Bystander response was observed only in CCRF-CEM and A549 cells (P bystander response on treatment with DMSO, suggests that ROS has a more significant role in mediating the bystander response.Since the possibility of the ROS and NO in mediating these bystander effect was confirmed, mechanistic control of these signaling molecules could either reduce radiation damage and potential carcinogenicity of normal tissues (by reducing bystander signaling) or maximize cell sterilization during chemotherapy (by amplifying bystander responses in tumors). PMID:29147282

Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

Science.gov (United States)

Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

2005-12-15

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

New in vitro system to predict chemotherapeutic efficacy of drug combinations in fresh tumor samples

Directory of Open Access Journals (Sweden)

Frank Christian Kischkel

2017-03-01

Full Text Available Background To find the best individual chemotherapy for cancer patients, the efficacy of different chemotherapeutic drugs can be predicted by pretesting tumor samples in vitro via the chemotherapy-resistance (CTR-Test®. Although drug combinations are widely used among cancer therapy, so far only single drugs are tested by this and other tests. However, several first line chemotherapies are combining two or more chemotherapeutics, leading to the necessity of drug combination testing methods. Methods We established a system to measure and predict the efficacy of chemotherapeutic drug combinations with the help of the Loewe additivity concept in combination with the CTR-test. A combination is measured by using half of the monotherapy’s concentration of both drugs simultaneously. With this method, the efficacy of a combination can also be calculated based on single drug measurements. Results The established system was tested on a data set of ovarian carcinoma samples using the combination carboplatin and paclitaxel and confirmed by using other tumor species and chemotherapeutics. Comparing the measured and the calculated values of the combination testings revealed a high correlation. Additionally, in 70% of the cases the measured and the calculated values lead to the same chemotherapeutic resistance category of the tumor. Conclusion Our data suggest that the best drug combination consists of the most efficient single drugs and the worst drug combination of the least efficient single drugs. Our results showed that single measurements are sufficient to predict combinations in specific cases but there are exceptions in which it is necessary to measure combinations, which is possible with the presented system.

Biological role in the transformation of platinum-group mineral grains

Science.gov (United States)

Reith, Frank; Zammit, Carla M.; Shar, Sahar S.; Etschmann, Barbara; Bottrill, Ralph; Southam, Gordon; Ta, Christine; Kilburn, Matthew; Oberthür, Thomas; Ball, Andrew S.; Brugger, Joël

2016-04-01

Platinum-group elements are strategically important metals. Finding new deposits is becoming increasingly difficult owing to our limited understanding of the processes that affect their mobility in surface environments. Microorganisms have been shown to promote the mobility of metals around ore deposits. Here we show that microorganisms influence the mobility of platinum-group elements in mineral grains collected from Brazil, Australia and Colombia. Scanning electron microscopy showed biofilms covering the platinum-group mineral grains. The biofilms contained abundant platinum-group element nanoparticles and microcrystalline aggregates, and were dominated by Proteobacteria, many of which were closely related to known metal-resistant species. Some platinum-group mineral grains contained carbon, nitrogen, sulfur, selenium and iodine, suggesting the grains may be biogenic in origin. Molecular analyses show that Brazilian platinum-palladium grains hosted specific bacterial communities, which were different in composition from communities associated with gold grains, or communities in surrounding soils and sediments. Nano-phase metallic platinum accumulated when a metallophillic bacterium was incubated with a percolating platinum-containing medium, suggesting that biofilms can cause the precipitation of mobile platinum complexes. We conclude that biofilms are capable of forming or transforming platinum-group mineral grains, and may play an important role for platinum-group element dispersion and re-concentration in surface environments.

Protein phosphatase 2A inhibition and circumvention of cisplatin cross-resistance by novel TCM-platinum anticancer agents containing demethylcantharidin.

Science.gov (United States)

To, Kenneth K W; Wang, Xinning; Yu, Chun Wing; Ho, Yee-Ping; Au-Yeung, Steve C F

2004-09-01

Novel TCM-platinum compounds [Pt(C(8)H(8)O(5))(NH(2)R)(2)] 1-5, derived from integrating demethylcantharidin, a modified component from a traditional Chinese medicine (TCM) with a platinum moiety, possess anticancer and protein phosphatase 2A inhibition properties. The compounds are able to circumvent cisplatin resistance by apparently targeting the DNA repair mechanism. Novel isosteric analogues [Pt(C(9)H(10)O(4))(NH(2)R)(2)] A and B, devoid of PP2A-inhibitory activity, were found to suffer from an enhanced DNA repair and were cross-resistant to cisplatin. The results advocate a well-defined structure-activity requirement associating the PP2A-inhibiting demethylcantharidin with the circumvention of cisplatin cross-resistance demonstrated by TCM-Pt compounds 1-5.

Biodistribution and pharamacokinetics of /sup 195m/Pt-labeled cis-dichlorotrans-dihydroxo-bis(isopropylamine)platinum(IV), CHIP, in normal female Fischer 344 rat

International Nuclear Information System (INIS)

Hoeschele, J.D.; Ferren, L.A.; Roberts, J.A.; Whitfield, L.R.

1983-01-01

The discovery and successful clinical application of the potent anti-tumor compound, cis-Dichlorodiammineplatinum(II), cis-DDP* has stimulated considerable interest in developing effective but less toxic second-generation platinum antitumor drugs. One such candidate drug is cis-Dichloro-trans-dihydroxo-bis-(isopropylamine)platinum(IV), cis-trans-[PtCl 2 (OH) 2 (i-PrNH 2 ) 2 ], (CHIP). An important feature of this Pt(IV) agent is that in addition to exhibiting a generally milder clinical toxicity than cisplatin, the dose-limiting toxicity of CHIP is the more common myelosuppression rather than the less desirable nephrotoxicity. Also, CHIP has been reported recently to be more effective than cisplatin against both alkylating agent sensitive and resistant strains of the Yoshida sarcoms. A microscale synthesis for /sup 195m/Pt-labelled CHIP and the tissue distribution and pharmacokinetic properties of this agent in normal female Fischer 344 rats are reported. A comparison with similar data for /sup 195m/Pt-cis-DDP is included

A rapid method for testing in vivo the susceptibility of different strains of Trypanosoma cruzi to active chemotherapeutic agents

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Leny S. Filardi

1984-06-01

Full Text Available A method is described which permits to determine in vivo an in a short period of time (4-6 hours the sensitivity of T. cruzo strains to known active chemotherapeutic agents. By using resistant- and sensitive T. cruzi stains a fairly good correlation was observed between the results obtained with this rapid method (which detects activity against the circulating blood forms and those obtained with long-term schedules which involve drug adminstration for at least 20 consecutive days and a prolonged period of assessment. This method may be used to characterize susceptibility to active drugs used clinically, provide infomation on the specific action against circulating trypomastigotes and screen active compounds. Differences in the natural susceptibility of Trypanosoma cruzi strains to active drugs have been already reported using different criteria, mostly demanding long-term study of the animal (Hauschka, 1949; Bock, Gonnert & Haberkorn, 1969; Brener, Costa & Chiari, 1976; Andrade & Figueira, 1977; Schlemper, 1982. In this paper we report a method which detects in 4-6 hours the effect of drugs on bloodstream forms in mice with established T. cruzi infections. The results obtained with this method show a fairly good correlation with those obtained by prolonged treatment schedules used to assess the action of drugs in experimental Chagas' disease and may be used to study the sensitivity of T. cruzi strains to active drugs.No presente trabalho descreve-se um metodo que permite determinar in vivo e em curto espaço de tempo (4-6 horas a sensibilidade de cepas de T. cruzi a agentes terapeuticos ativos na doença de Chagas. Usando-se cepas sensíveis e resistentes aos medicamentos foi possível observar uma boa correlação entre os resultados obtidos com o método rápido (que detecta atividade contra as formas circulantes do parasita e aqueles obtidos com esquema de acao prolongada que envolve a administração da droga por 20 dias e posterior avalia

In vitro chemosensitivity based on depth of invasion in advanced colorectal cancer using ATP-based chemotherapy response assay (ATP-CRA).

Science.gov (United States)

Cho, Y B; Lee, W Y; Song, S Y; Choi, S H; Shin, H J; Ahn, K-D; Lee, J M; Kim, H C; Yun, S H; Chun, H-K

2009-09-01

Tumors are composed of subpopulations of cells with heterogeneous characteristics that allow for tumor progression and development of treatment resistance. The purpose of this study was to determine if there is heterogeneity in the in vitro chemosensitivity in different invasive sections of a single tumor. Chemosensitivity in advanced colorectal cancer specimens was examined using an ATP-based chemotherapy response assay. Four chemotherapeutic agents (5-fluorouracil (5-FU), oxaliplatin, irinotecan, and mitomycin) were used for chemosensitivity studies. Tumor tissues were obtained from the superficial (mucosa/submucosa) and deep parts (muscle/subserosa/serosa), respectively. Twenty patients who had results for both the superficial and deep parts were evaluated. The chemosensitivity study showed variable cell death rates in both parts of the tumor. Regression analysis showed some correlations with 5-FU and irinotecan, but not with oxaliplatin or mitomycin. With the exception of three patients in whom no drug was recommended, at least one chemotherapeutic drug showed some consistency between the superficial and deep parts of the tumor. Mitomycin was the most frequently active agent for the superficial part. In the deep part, oxaliplatin and mitomycin were the most active agents. There may be heterogeneity in the responses to anti-chemotherapeutic agents in advanced colorectal cancer, according to the depth of invasion. Therefore, in clinical situations, chemosensitivity test specimens should be mixed with various parts of the whole tumor in order to obtain representative chemosensitivity and chemoresistance profiles.

Novel 3-(aminomethyl)naphthoquinone mannich base-platinum(IV) complexes: synthesis, characterization, electrochemical and cytotoxic studies

Energy Technology Data Exchange (ETDEWEB)

Silva, Gustavo B. da; Neves, Amanda P.; Vargas, Maria D., E-mail: mdvargas@vm.uff.br [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Instituto de Quimica; Alves, Wagner A. [Universidade Federal Rural do Rio de Janeiro (UFRRJ), Seropedica, RJ (Brazil). Departamento de Quimica; Marinho-Filho, Jose D.B.; Pessoa, Claudia; Moraes, Manoel O.; Costa-Lotufo, Leticia V. [Universidade Federal do Ceara (UFCE), Fortaleza, CE (Brazil). Centro de Ciencias da Saude. Departamento de Fisiologia e Farmacologia

2013-04-15

Three novel platinum(IV) complexes cis,cis,trans-[Pt(HL1-3)Cl{sub 2}(OH){sub 2}] 1b-3b(HL = 2-hydroxy-3-[(R{sup 1} -amino)(pyridin-2-yl)methyl]-1,4-naphthoquinone, R{sup 1} = n-butyl, HL1; n-heptyl, HL2 and n-decyl, HL3) have been obtained from the oxidation of the respective precursors cis-[Pt(HL1-3)Cl{sub 2}] 1a-3a. Cyclic voltammetry studies of 1b-3b in MeCN showed the quasi reversible naphthoquinonate (NQO{sup -}, i.e., L{sup -}) redox process and irreversible process attributed to the reduction of the Pt{sup 4+}/Pt{sup 2+} pair, at potentials about 400 mV less negative than for the cisplatin precursor cis,cis,trans-[Pt(NH{sub 3}){sub 2}Cl{sub 2}(OH){sub 2}]. Hydrogen bond interaction between the naphthoquinone 2-hydroxyl group and an axially coordinated hydroxide ligand in 1b-3b has been proposed to favor the Pt{sup 4+}/Pt{sup 2+} reduction. The cytotoxicity studies against four human cancer cell lines have shown that in general the platinum(IV) and platinum(II)derivatives exhibit the same cytotoxic profile and are all more active than cisplatin. The lowest in vitro IC{sub 50} values have been observed for 2b-3b, which bear ligands with the largest R{sup 1} groups (HL2-HL3) being the most lipophilic. Furthermore similar IC{sub 50} values for platinum(II) and platinum(IV) complexes of the same ligands have been associated with rapid in vitro reduction of the latter complexes to afford 1a-3a. (author)

Assurance in Agent-Based Systems

Energy Technology Data Exchange (ETDEWEB)

Gilliom, Laura R.; Goldsmith, Steven Y.

1999-05-10

Our vision of the future of information systems is one that includes engineered collectives of software agents which are situated in an environment over years and which increasingly improve the performance of the overall system of which they are a part. At a minimum, the movement of agent and multi-agent technology into National Security applications, including their use in information assurance, is apparent today. The use of deliberative, autonomous agents in high-consequence/high-security applications will require a commensurate level of protection and confidence in the predictability of system-level behavior. At Sandia National Laboratories, we have defined and are addressing a research agenda that integrates the surety (safety, security, and reliability) into agent-based systems at a deep level. Surety is addressed at multiple levels: The integrity of individual agents must be protected by addressing potential failure modes and vulnerabilities to malevolent threats. Providing for the surety of the collective requires attention to communications surety issues and mechanisms for identifying and working with trusted collaborators. At the highest level, using agent-based collectives within a large-scale distributed system requires the development of principled design methods to deliver the desired emergent performance or surety characteristics. This position paper will outline the research directions underway at Sandia, will discuss relevant work being performed elsewhere, and will report progress to date toward assurance in agent-based systems.

Assurance in Agent-Based Systems

International Nuclear Information System (INIS)

Gilliom, Laura R.; Goldsmith, Steven Y.

1999-01-01

Our vision of the future of information systems is one that includes engineered collectives of software agents which are situated in an environment over years and which increasingly improve the performance of the overall system of which they are a part. At a minimum, the movement of agent and multi-agent technology into National Security applications, including their use in information assurance, is apparent today. The use of deliberative, autonomous agents in high-consequence/high-security applications will require a commensurate level of protection and confidence in the predictability of system-level behavior. At Sandia National Laboratories, we have defined and are addressing a research agenda that integrates the surety (safety, security, and reliability) into agent-based systems at a deep level. Surety is addressed at multiple levels: The integrity of individual agents must be protected by addressing potential failure modes and vulnerabilities to malevolent threats. Providing for the surety of the collective requires attention to communications surety issues and mechanisms for identifying and working with trusted collaborators. At the highest level, using agent-based collectives within a large-scale distributed system requires the development of principled design methods to deliver the desired emergent performance or surety characteristics. This position paper will outline the research directions underway at Sandia, will discuss relevant work being performed elsewhere, and will report progress to date toward assurance in agent-based systems

Plant-Derived Urease Inhibitors as Alternative Chemotherapeutic Agents.

Science.gov (United States)

Hassan, Sherif T S; Žemlička, Milan

2016-07-01

Inhibition of the metalloenzyme urease has important pharmacologic applications in the field of antiulcer and antigastric cancer agents. Urease is involved in many serious infections caused by Helicobacter pylori in the gastric tract as well as by Proteus and related species in the urinary tract. Although numerous studies have described several novel urease inhibitors (UIs) used for the treatment of gastric and urinary infections, all these compounds have exhibited severe side effects, toxicity, and instability. Therefore, to overcome such problems, it is necessary to search for new sources of UIs, such as natural products, that provide reduced side effects, low toxicity, greater stability, and bioavailability. As limited studies have been conducted on plant-derived UIs, this paper aims to highlight and summarize the most promising compounds isolated and identified from plants, such as terpenoids, phenolic compounds, alkaloids, and other substances with inhibitory activities against plant and bacterial ureases; these are in vitro and in vivo studies with an emphasis on structure-activity relationship studies and types of inhibition that show high and promising levels of anti-urease activity. This will aid medicinal chemists in the design and synthesis of novel and pharmacologically potent UIs useful for the development of antiulcer drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

SERIES: Genomic instability in cancer Balancing repair and tolerance of DNA damage caused by alkylating agents

OpenAIRE

Fu, Dragony; Calvo, Jennifer A.; Samson, Leona D

2012-01-01

Alkylating agents comprise a major class of frontline chemotherapeutic drugs that inflict cytotoxic DNA damage as their main mode of action, in addition to collateral mutagenic damage. Numerous cellular pathways, including direct DNA damage reversal, base excision repair (BER), and mismatch repair (MMR) respond to alkylation damage to defend against alkylation-induced cell death or mutation. However, maintaining a proper balance of activity both within and between these pathways is crucial fo...

Agent-based modeling of sustainable behaviors

CERN Document Server

Sánchez-Maroño, Noelia; Fontenla-Romero, Oscar; Polhill, J; Craig, Tony; Bajo, Javier; Corchado, Juan

2017-01-01

Using the O.D.D. (Overview, Design concepts, Detail) protocol, this title explores the role of agent-based modeling in predicting the feasibility of various approaches to sustainability. The chapters incorporated in this volume consist of real case studies to illustrate the utility of agent-based modeling and complexity theory in discovering a path to more efficient and sustainable lifestyles. The topics covered within include: households' attitudes toward recycling, designing decision trees for representing sustainable behaviors, negotiation-based parking allocation, auction-based traffic signal control, and others. This selection of papers will be of interest to social scientists who wish to learn more about agent-based modeling as well as experts in the field of agent-based modeling.

Synthesis and characterization of Cu(II)-based anticancer chemotherapeutic agent targeting topoisomerase Iα: in vitro DNA binding, pBR322 cleavage, molecular docking studies and cytotoxicity against human cancer cell lines.

Science.gov (United States)

Tabassum, Sartaj; Zaki, Mehvash; Afzal, Mohd; Arjmand, Farukh

2014-03-03

New metal-based anticancer chemotherapeutic drug candidates [Cu(phen)L](NO₃)₂ (1) and [Zn(phen)L](NO₃)₂ (2) were synthesized from ligand L (derived from pharmacophore scaffold barbituric acid and pyrazole). In vitro DNA binding studies of the L, 1 and 2 were carried out by various biophysical techniques revealing electrostatic mode. Complex 1 cleaves pBR322 DNA via oxidative pathway and recognizes major groove of DNA double helix. The molecular docking study was carried out to ascertain the mode of action towards the molecular target DNA and enzymes. The complex 1 exhibited remarkably good anticancer activity on a panel of human cancer cell lines (GI₅₀ values < 10 μg/ml), and to elucidate the mechanism of cancer inhibition, Topo-I enzymatic activity was carried out. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Pharmacological agents and impairment of fracture healing: what is the evidence?

NARCIS (Netherlands)

Pountos, I.; Georgouli, T.; Blokhuis, T.J.; Pape, H.C.; Giannoudis, P.V.

2008-01-01

Bone healing is an extremely complex process which depends on the coordinated action of several cell lineages on a cascade of biological events, and has always been a major medical concern. The use of several drugs such as corticosteroids, chemotherapeutic agents, non-steroidal anti-inflammatory

Agent-Based Optimization

CERN Document Server

Jędrzejowicz, Piotr; Kacprzyk, Janusz

2013-01-01

This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

Characterization of electrochemically modified polycrystalline platinum surfaces

Energy Technology Data Exchange (ETDEWEB)

Krebs, L.C.; Ishida, Takanobu.

1991-12-01

The characterization of electrochemically modified polycrystalline platinum surfaces has been accomplished through the use of four major electrochemical techniques. These were chronoamperometry, chronopotentiommetry, cyclic voltammetry, and linear sweep voltammetry. A systematic study on the under-potential deposition of several transition metals has been performed. The most interesting of these were: Ag, Cu, Cd, and Pb. It was determined, by subjecting the platinum electrode surface to a single potential scan between {minus}0.24 and +1.25 V{sub SCE} while stirring the solution, that the electrocatalytic activity would be regenerated. As a consequence of this study, a much simpler method for producing ultra high purity water from acidic permanganate has been developed. This method results in water that surpasses the water produced by pyrocatalytic distillation. It has also been seen that the wettability of polycrystalline platinum surfaces is greatly dependent on the quantity of oxide present. Oxide-free platinum is hydrophobic and gives a contact angle in the range of 55 to 62 degrees. We have also modified polycrystalline platinum surface with the electrically conducting polymer poly-{rho}-phenylene. This polymer is very stable in dilute sulfuric acid solutions, even under applied oxidative potentials. It is also highly resistant to electrochemical hydrogenation. The wettability of the polymer modified platinum surface is severely dependent on the choice of supporting electrolyte chosen for the electrochemical polymerization. Tetraethylammonium tetrafluoroborate produces a film that is as hydrophobic as Teflon, whereas tetraethylammonium perchlorate produces a film that is more hydrophilic than oxide-free platinum.

Characterization of electrochemically modified polycrystalline platinum surfaces

Energy Technology Data Exchange (ETDEWEB)

Krebs, Leonard C. [State Univ. of New York (SUNY), Stony Brook, NY (United States); Ishida, Takanobu [State Univ. of New York (SUNY), Stony Brook, NY (United States)

1991-12-01

The characterization of electrochemically modified polycrystalline platinum surfaces has been accomplished through the use of four major electrochemical techniques. These were chronoamperometry, chronopotentiommetry, cyclic voltammetry, and linear sweep voltammetry. A systematic study on the under-potential deposition of several transition metals has been performed. The most interesting of these were: Ag, Cu, Cd, and Pb. It was determined, by subjecting the platinum electrode surface to a single potential scan between -0.24 and +1.25 V_SCE while stirring the solution, that the electrocatalytic activity would be regenerated. As a consequence of this study, a much simpler method for producing ultra high purity water from acidic permanganate has been developed. This method results in water that surpasses the water produced by pyrocatalytic distillation. It has also been seen that the wettability of polycrystalline platinum surfaces is greatly dependent on the quantity of oxide present. Oxide-free platinum is hydrophobic and gives a contact angle in the range of 55 to 62 degrees. We have also modified polycrystalline platinum surface with the electrically conducting polymer poly-ρ-phenylene. This polymer is very stable in dilute sulfuric acid solutions, even under applied oxidative potentials. It is also highly resistant to electrochemical hydrogenation. The wettability of the polymer modified platinum surface is severely dependent on the choice of supporting electrolyte chosen for the electrochemical polymerization. Tetraethylammonium tetrafluoroborate produces a film that is as hydrophobic as Teflon, whereas tetraethylammonium perchlorate produces a film that is more hydrophilic than oxide-free platinum.

Down-regulation of DNA mismatch repair proteins in human and murine tumor spheroids: implications for multicellular resistance to alkylating agents.

Science.gov (United States)

Francia, Giulio; Green, Shane K; Bocci, Guido; Man, Shan; Emmenegger, Urban; Ebos, John M L; Weinerman, Adina; Shaked, Yuval; Kerbel, Robert S

2005-10-01

Similar to other anticancer agents, intrinsic or acquired resistance to DNA-damaging chemotherapeutics is a major obstacle for cancer therapy. Current strategies aimed at overcoming this problem are mostly based on the premise that tumor cells acquire heritable genetic mutations that contribute to drug resistance. Here, we present evidence for an epigenetic, tumor cell adhesion-mediated, and reversible form of drug resistance that is associated with a reduction of DNA mismatch repair proteins PMS2 and/or MLH1 as well as other members of this DNA repair process. Growth of human breast cancer, human melanoma, and murine EMT-6 breast cancer cell lines as multicellular spheroids in vitro, which is associated with increased resistance to many chemotherapeutic drugs, including alkylating agents, is shown to lead to a reproducible down-regulation of PMS2, MLH1, or, in some cases, both as well as MHS6, MSH3, and MSH2. The observed down-regulation is in part reversible by treatment of tumor spheroids with the DNA-demethylating agent, 5-azacytidine. Thus, treatment of EMT-6 mouse mammary carcinoma spheroids with 5-azacytidine resulted in reduced and/or disrupted cell-cell adhesion, which in turn sensitized tumor spheroids to cisplatin-mediated killing in vitro. Our results suggest that antiadhesive agents might sensitize tumor spheroids to alkylating agents in part by reversing or preventing reduced DNA mismatch repair activity and that the chemosensitization properties of 5-azacytidine may conceivably reflect its role as a potential antiadhesive agent as well as reversal agent for MLH1 gene silencing in human tumors.

Repurposing the FDA-approved pinworm drug pyrvinium as a novel chemotherapeutic agent for intestinal polyposis.

Directory of Open Access Journals (Sweden)

Bin Li

Full Text Available Mutations in the WNT-pathway regulator ADENOMATOUS POLYPOSIS COLI (APC promote aberrant activation of the WNT pathway that is responsible for APC-associated diseases such as Familial Adenomatous Polyposis (FAP and 85% of spontaneous colorectal cancers (CRC. FAP is characterized by multiple intestinal adenomas, which inexorably result in CRC. Surprisingly, given their common occurrence, there are few effective chemotherapeutic drugs for FAP. Here we show that the FDA-approved, anti-helminthic drug Pyrvinium attenuates the growth of WNT-dependent CRC cells and does so via activation of CK1α. Furthermore, we show that Pyrvinium can function as an in vivo inhibitor of WNT-signaling and polyposis in a mouse model of FAP: APCmin mice. Oral administration of Pyrvinium, a CK1α agonist, attenuated the levels of WNT-driven biomarkers and inhibited adenoma formation in APCmin mice. Considering its well-documented safe use for treating enterobiasis in humans, our findings suggest that Pyrvinium could be repurposed for the clinical treatment of APC-associated polyposes.

Corrosion Studies of Platinum Nano-Particles for Fuel Cells

DEFF Research Database (Denmark)

Shim, Signe Sarah

The main focus of the present thesis is on corrosion and prevention of corrosion of platinum particles supported on carbon. This is important for instance in connection with start up and shutdown of fuel cells. The degradation mechanism of platinum particles supported on carbon has been character......The main focus of the present thesis is on corrosion and prevention of corrosion of platinum particles supported on carbon. This is important for instance in connection with start up and shutdown of fuel cells. The degradation mechanism of platinum particles supported on carbon has been...... characterized during oxygen reduction reaction (ORR) condition using identical location (IL) transmission electron microscopy (TEM). A TEM grid was used as the working electrode in an electrochemical setup allowing a direct correlation between the electrochemical response and the TEM analysis. The main results...... thirds and one monolayer of gold on platinum supported on carbon were synthesized by an inverse micelle method. The results obtained appear independent of the gold coverage. It has been shown that the electrochemical active surface areas of the platinum and platinum gold particles synthesized...

Reaction pathways for reduction of nitrate ions on platinum, rhodium, and platinum-rhodium alloy electrodes

International Nuclear Information System (INIS)

Cunha, M.C.P.M. da; De Souza, J.P.I.; Nart, F.C.

2000-01-01

The reduction of nitrate ions on platinum, rhodium, and platinum-rhodium alloy electrodes has been investigated using differential electrochemical mass spectrometry and in situ FTIR measurements. For 3 M HNO 3 concentration it has been found that nitrate starts the reduction with partial N-O bond dissociation and N-N bond formation generating NO and N 2 O. At potentials lower than 0.2 V the reaction proceeds forming dissolved NH 4 + . For potentials lower than 0 V the reduction continues via a multiple pathway reaction leading to the nonselective production of N 2 , NH 2 OH, and N 2 H 2 . On the alloyed electrodes, the production of NO and N 2 O has been observed in both cathodic and anodic scans, while on pure platinum and rhodium electrodes the reaction has been observed only during the cathodic scan. Contrasting with the pure platinum and rhodium alloys, where the N-O bond break starts forming NO and N 2 O, on the alloys HNO 2 has been observed as the first reaction step. For alloys with higher rhodium composition, like Pt 75 Rh 25 , no N 2 has been detected for potentials lower than 0 V

Fluoropyrimidine and platinum toxicity pharmacogenetics: an umbrella review of systematic reviews and meta-analyses.

Science.gov (United States)

Campbell, Jared M; Bateman, Emma; Peters, Micah Dj; Bowen, Joanne M; Keefe, Dorothy M; Stephenson, Matthew D

2016-03-01

Fluoropyrimidine (FU) and platinum-based chemotherapies are greatly complicated by their associated toxicities. This umbrella systematic review synthesized all systematic reviews that investigated associations between germline variations and toxicity, with the aim of informing personalized medicine. Systematic reviews are important in pharmacogenetics where false positives are common. Four systematic reviews were identified for FU-induced toxicity and three for platinum. Polymorphisms of DPYD and TYMS, but not MTHFR, were statistically significantly associated with FU-induced toxicity (although only DPYD had clinical significance). For platinum, GSTP1 was found to not be associated with toxicity. This umbrella systematic review has synthesized the best available evidence on the pharmacogenetics of FU and platinum toxicity. It provides a useful reference for clinicians and identifies important research gaps.

Comparison of clinical outcome after first-line platinum-based chemotherapy in different types of KRAS mutated advanced non-small-cell lung cancer.

Science.gov (United States)

Mellema, Wouter W; Masen-Poos, Lucie; Smit, Egbert F; Hendriks, Lizza E L; Aerts, Joachim G; Termeer, Arien; Goosens, Martijn J; Smit, Hans J M; van den Heuvel, Michel M; van der Wekken, Anthonie J; Herder, Gerarda J M; Krouwels, Frans H; Stigt, Jos A; van den Borne, Ben E E M; Haitjema, Tjeerd J; Staal-Van den Brekel, Agnes J; van Heemst, Robbert C; Pouw, Ellen; Dingemans, Anne-Marie C

2015-11-01

As suggested by in-vitro data, we hypothesize that subtypes of KRAS mutated non-small cell lung cancer (NSCLC) respond differently to chemotherapy regimens. Patients with advanced NSCLC and known KRAS mutation, treated with first-line platinum-based chemotherapy, were retrieved from hospital databases. to investigate overall response rate (ORR), progression free survival (PFS) and overall survival (OS) between different types of platinum-based chemotherapy per type of KRAS mutation. 464 patients from 17 hospitals, treated between 2000 and 2013, were included. The majority of patients had stage IV disease (93%), had a history of smoking (98%) and known with an adenocarcinoma (91%). Most common types of KRAS mutation were G12C (46%), G12V (20%) and G12D (10%). Platinum was combined with pemetrexed (n=334), taxanes (n=68) or gemcitabine (n=62). Patients treated with taxanes had a significant improved ORR (50%) compared to pemetrexed (21%) or gemcitabine (25%; pchemotherapy had best ORR. Response to chemotherapy regimens was different in types of KRAS mutation. Especially patients with G12V had better response to taxane treatment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Major Clinical Impact of Platinum-Based Chemotherapy in a Patient with a Borderline Ovarian Cancer

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Jian Chen

2009-09-01

Full Text Available A patient with extensive and painful chest wall involvement from a metastatic borderline cancer of the ovary was treated with a carboplatin plus paclitaxel chemotherapy regimen. She achieved a rather dramatic improvement of pain control, a significant biochemical response with 75% reduction of the CA-125 antigen level, but only limited radiographic tumor regression. This experience emphasizes the potential clinical utility of platinum-based cytotoxic chemotherapy in the setting of symptomatic advanced borderline ovarian cancer.

A matched-pair comparison of intensity-modulated radiation therapy with cetuximab versus intensity-modulated radiation therapy with platinum-based chemotherapy for locally advanced head neck cancer

International Nuclear Information System (INIS)

Huang, J.; Baschnagel, A.M.; Chen, P.; Ye, H.; Krauss, D.; Gustafson, G.; Jaiyesmi, I.; Folbe, M.; Akervall, J.

2014-01-01

We retrospectively compared the efficacy of intensity-modulated radiotherapy (IMRT) and cetuximab (IMRT/cetuximab) versus IMRT and platinum-based chemotherapy (IMRT/platinum) for locally advanced head neck squamous cell carcinoma (LAHNSCC). Thirty-one IMRT/cetuximab patients were matched 1:2 with 62 IMRT/platinum patients according to primary site and clinical stage. The primary endpoint was locoregional recurrence (LRR), and secondary endpoints included distant metastasis (DM), cause-specific survival (CSS), and overall survival (OS). Because of inherent selection bias, the IMRT/cetuximab cohort was significantly older and with a higher Charlson Comorbidity Index. IMRT/cetuximab and IMRT/platinum did not have significantly different LRR and DM (33 vs. 23% at 2 years, P=0.22; 17 vs. 11% at 2 years, P=0.40; respectively). IMRT/cetuximab had significantly worse CSS and OS (67 vs. 84%, P=0.04; 58 vs. 83%, P=0.001; respectively). However, for the subset of elderly patients ≥65 years old, there is no difference between the two cohorts for all endpoints (all P=NS). IMRT/platinum should remain the preferred choice of chemoradiotherapy for LAHNSCC, but IMRT/cetuximab may be a reasonable alternative for elderly patients. (author)

Security Framework for Agent-Based Cloud Computing

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K Venkateshwaran

2015-06-01

Full Text Available Agent can play a key role in bringing suitable cloud services to the customer based on their requirements. In agent based cloud computing, agent does negotiation, coordination, cooperation and collaboration on behalf of the customer to make the decisions in efficient manner. However the agent based cloud computing have some security issues like (a. addition of malicious agent in the cloud environment which could demolish the process by attacking other agents, (b. denial of service by creating flooding attacks on other involved agents. (c. Some of the exceptions in the agent interaction protocol such as Not-Understood and Cancel_Meta protocol can be misused and may lead to terminating the connection of all the other agents participating in the negotiating services. Also, this paper proposes algorithms to solve these issues to ensure that there will be no intervention of any malicious activities during the agent interaction.

Developing Inhibitors of Translesion DNA Synthesis as Therapeutic Agents Against Lung Cancer

Science.gov (United States)

2014-10-01

pol eta when replicating damaged DNA. 1S. SUBJECT TERMS: Mutagenesis, DNA polymerases, nucleoside analogs, chemotherapeutic agents 16. SECURITY ...such as polymerase eta, iota , and kappa that are involved in replicating damaged DNA. Our kinetic data obtained under Task 1B indicates that pol eta

Platinum stable isotopes in ferromanganese crust and nodules

Science.gov (United States)

Corcoran, Loretta; Seward, Terry; Handler, Monica R.

2015-04-01

Hydrogenetic ferromanganese (Fe-Mn) crust and nodules are slow-growing chemical sediments that form by direct precipitation from seawater, resulting in a record of changing seawater chemistry. These sediments are the primary sink for platinum in the modern oxic marine environment, hosting well-documented enrichments over other platinum-group elements (PGEs): the Pt anomaly [1]. Platinum is a non-bio-essential, highly siderophile, transition metal with six stable isotopes (190Pt, 192Pt, 194Pt, 195Pt, 196Pt, and 198Pt) with several oxidation states (Pt0, Pt2+ and Pt4+). Platinum is generally considered to exist in the hydrosphere as Pt2+ although its behaviour in the marine environment is poorly constrained, and Pt4+may also be present. Variations in ocean redox state, together with changes in source fluxes to the oceans, may therefore lead to small variations (Leaching experiments conducted on platinum rich terrestrial materials underwent platinum stable isotopic measurement as an analogue for the Pt isotopic fractionation associated with continental weathering. [1] Hodge, V.F. et al. (1985) Earth and Planetary Science Letters, 72, 158-162. [2] Creech, J. et al. (2013) Journal of Analytical Atomic Spectrometry, 28. 853-865.

The influence of toxicity constraints in models of chemotherapeutic protocol escalation

KAUST Repository

Boston, E. A. J.

2011-04-06

The prospect of exploiting mathematical and computational models to gain insight into the influence of scheduling on cancer chemotherapeutic effectiveness is increasingly being considered. However, the question of whether such models are robust to the inclusion of additional tumour biology is relatively unexplored. In this paper, we consider a common strategy for improving protocol scheduling that has foundations in mathematical modelling, namely the concept of dose densification, whereby rest phases between drug administrations are reduced. To maintain a manageable scope in our studies, we focus on a single cell cycle phase-specific agent with uncomplicated pharmacokinetics, as motivated by 5-Fluorouracil-based adjuvant treatments of liver micrometastases. In particular, we explore predictions of the effectiveness of dose densification and other escalations of the protocol scheduling when the influence of toxicity constraints, cell cycle phase specificity and the evolution of drug resistance are all represented within the modelling. For our specific focus, we observe that the cell cycle and toxicity should not simply be neglected in modelling studies. Our explorations also reveal the prediction that dose densification is often, but not universally, effective. Furthermore, adjustments in the duration of drug administrations are predicted to be important, especially when dose densification in isolation does not yield improvements in protocol outcomes. © The author 2011. Published by Oxford University Press on behalf of the Institute of Mathematics and its Applications. All rights reserved.

Sustained platelet-sparing effect of weekly low dose paclitaxel allows effective, tolerable delivery of extended dose dense weekly carboplatin in platinum resistant/refractory epithelial ovarian cancer

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Blagden Sarah

2011-07-01

Full Text Available Abstract Background Platinum agents have shown demonstrable activity in the treatment of patients with platinum resistant, recurrent ovarian cancer when delivered in a "dose-dense" fashion. However, the development of thrombocytopenia limits the weekly administration of carboplatin to no greater than AUC 2. Paclitaxel has a well-described platelet sparing effect however its use to explicitly provide thromboprotection in the context of dose dense carboplatin has not been explored. Methods We treated seven patients with platinum resistant ovarian cancer who had previously received paclitaxel or who had developed significant peripheral neuropathy precluding the use of further full dose weekly paclitaxel. Results We were able to deliver carboplatin AUC 3 and paclitaxel 20 mg/m2 with no thrombocytopenia or worsening of neuropathic side-effects, and with good activity. Conclusions We conclude that this regimen may be feasible and active, and could be formally developed as a "platinum-focussed dose-dense scaffold" into which targeted therapies that reverse platinum resistance can be incorporated, and merits further evaluation.

Phosphorescent Organic Light Emitting Diodes Implementing Platinum Complexes

Science.gov (United States)

Ecton, Jeremy Exton

Organic light emitting diodes (OLEDs) are a promising approach for display and solid state lighting applications. However, further work is needed in establishing the availability of efficient and stable materials for OLEDs with high external quantum efficiency's (EQE) and high operational lifetimes. Recently, significant improvements in the internal quantum efficiency or ratio of generated photons to injected electrons have been achieved with the advent of phosphorescent complexes with the ability to harvest both singlet and triplet excitons. Since then, a variety of phosphorescent complexes containing heavy metal centers including Os, Ni, Ir, Pd, and Pt have been developed. Thus far, the majority of the work in the field has focused on iridium based complexes. Platinum based complexes, however, have received considerably less attention despite demonstrating efficiency's equal to or better than their iridium analogs. In this study, a series of OLEDs implementing newly developed platinum based complexes were demonstrated with efficiency's or operational lifetimes equal to or better than their iridium analogs for select cases. In addition to demonstrating excellent device performance in OLEDs, platinum based complexes exhibit unique photophysical properties including the ability to form excimer emission capable of generating broad white light emission from a single emitter and the ability to form narrow band emission from a rigid, tetradentate molecular structure for select cases. These unique photophysical properties were exploited and their optical and electrical properties in a device setting were elucidated. Utilizing the unique properties of a tridentate Pt complex, Pt-16, a highly efficient white device employing a single emissive layer exhibited a peak EQE of over 20% and high color quality with a CRI of 80 and color coordinates CIE(x=0.33, y=0.33). Furthermore, by employing a rigid, tetradentate platinum complex, PtN1N, with a narrow band emission into a

Nanomedicine for cancer therapy from chemotherapeutic to hyperthermia-based therapy

CERN Document Server

Kumar, Piyush

2017-01-01

This Brief focuses on the cancer therapy available till date, from conventional drug delivery to nanomedicine in clinical trial. In addition, it reports on future generation based nanotherapeutics and cancer theranostic agent for effective therapeutic diagnosis and treatment. Breast cancer was chosen as the model system in this review. The authors give emphasis to multiple drug resistance (MDR) and its mechanism and how to overcome it using the nanoparticle approach. .

Econophysics of agent-based models

CERN Document Server

Aoyama, Hideaki; Chakrabarti, Bikas; Chakraborti, Anirban; Ghosh, Asim

2014-01-01

The primary goal of this book is to present the research findings and conclusions of physicists, economists, mathematicians and financial engineers working in the field of "Econophysics" who have undertaken agent-based modelling, comparison with empirical studies and related investigations. Most standard economic models assume the existence of the representative agent, who is “perfectly rational” and applies the utility maximization principle when taking action. One reason for this is the desire to keep models mathematically tractable: no tools are available to economists for solving non-linear models of heterogeneous adaptive agents without explicit optimization. In contrast, multi-agent models, which originated from statistical physics considerations, allow us to go beyond the prototype theories of traditional economics involving the representative agent. This book is based on the Econophys-Kolkata VII Workshop, at which many such modelling efforts were presented. In the book, leading researchers in the...

Iodometric determination of platinum(4) using amperometry

International Nuclear Information System (INIS)

Zakharov, V.A.; Gavva, N.F.; Songina, O.A.

1976-01-01

The possibility of iodometric determination of platinum (4) by amperometric titration has been investigated. Titration has been conducted at zero potential of platinum reference electrode. Voltampere curves and absorption spectra of the solutions have been recorded to elucidate the nature of platinum (4) interaction with iodide-ion. It has been established that in the case of small excess of iodide complex [PtI 6 ] 2- is formed. When there is a considerable excess of KI, platinum (4) is reduced to Pt(2) with the formation of [PtI 4 ] 2 - and liberation of free iodine. Optimal for iodometric titration of Pt(4) is the use of acetate ot phosphate background solution with pH 6-8 with respect to 1M KI which is attained by adding 3 g of solid KI to 20 ml of the solution being titrated. Under these conditions the limit of platinum detection is 0.5 mkg/ml. Determination of Pt (4) is not hindered by the presence of 200-fold amounts of Cr(6), V(5), and Ni(2) as well as by 20-10-fold amounts of As(5), Sb(5), Se(4), Te(4), Rh(3), and Ir(3), Determination is hindered by the presence of Pd(2), Fe(3), Ir(4), and Cu(2) which, however, can easily be overcome. The possibility has been shown of using the developed technique for analysis of platinum catalysts and alloys

Elevated serum levels of vascular endothelial growth factor predict a poor prognosis of platinum-based chemotherapy in non-small cell lung cancer

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Zang JL

2017-01-01

Full Text Available Jialan Zang,1–3,* Yong Hu,1,2,* Xiaoyue Xu,1,2 Jie Ni,1,2 Dali Yan,1,2 Siwen Liu,4 Jieyu He,5 Jing Xue,4 Jianzhong Wu,4 Jifeng Feng2 1The Fourth Clinical School of Nanjing Medical University, 2Department of Chemotherapy, Nanjing Medical University Affiliated Cancer Hospital, Nanjing, 3Department of Oncology, The First Hospital of Harbin City, Harbin, 4Center of Clinical Laboratory, Nanjing Medical University Affiliated Cancer Hospital, 5Department of Public Health, Southeast University, Nanjing, People’s Republic of China *These authors contributed equally to this work Aim: This study was designed to investigate the predictive and prognostic values of serum vascular endothelial growth factor (VEGF level in non-small cell lung cancer (NSCLC patients treated with platinum-based chemotherapy. Methods: Patients’ peripheral blood samples were collected prior to chemotherapy and after 1 week of the third cycle of combination chemotherapy. Serum VEGF levels were evaluated through Luminex multiplex technique. Between September 2011 and August 2015, a total of 135 consecutive advanced or recurrent histologically verified NSCLC patients were enrolled in the study. Moreover, all the patients received platinum-based combination chemotherapy as a first-line treatment. Results: No significant associations were found between pretreatment serum VEGF levels and clinical characteristics, such as sex (P=0.0975, age (P=0.2522, stage (P=0.1407, lymph node metastasis (P=0.6409, tumor location (P=0.3520, differentiated degree (P=0.5608, pathological (histological type (P=0.4885, and response to treatment (P=0.9859. The VEGF load per platelet (VEGFPLT levels were not correlated with sex, age, primary tumor site, and pathological type in NSCLC patients (all P>0.05. The median survival time of progression-free survival (PFS was 6.407 and 5.29 months in the low and high groups, respectively, when using 280 pg/mL VEGF level as the cutoff point (P=0.024. Conclusion

Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic-induced neuropathic pain.

Science.gov (United States)

Tomohisa, Mori; Junpei, Ohya; Aki, Masumoto; Masato, Harumiya; Mika, Fukase; Kazumi, Yoshizawa; Teruo, Hayashi; Tsutomu, Suzuki

2015-11-01

Previous studies have shown that ligands of the sigma-1 receptor chaperone (Sig-1R) regulate pain-related behaviors. Clinical use of chemotherapeutics is often compromised due to their adverse side effects, particularly those related to neuropathy. Previous studies have shown that repeated administration of oxaliplatin and paclitaxel produces neuropathy in rodents. Therefore, the aim of the present study was to clarify the involvement of the Sig-1R in chemotherapeutic-induced neuropathy by examining the effects of oxaliplatin and paclitaxel on the Sig-1R levels in the spinal cord, and by examining the effects of Sig-1R agonist and antagonist on oxaliplatin- and paclitaxel-induced neuropathy in rats. Chemotherapeutic-induced neuropathic pain was accompanied by a significant reduction of the Sig-1R level in the spinal cord. Furthermore, the administration of paclitaxel to CHO cells that stably overexpressed Sig-1Rs induced the clustering of Sig-1Rs. We also found that the Sig-1R agonist SA4503 potently inhibited the neuropathy induced by oxaliplatin- and paclitaxel, whereas this action was abolished by the Sig-1R antagonist NE-100. These results suggest that the reduction of Sig-1R activity is involved in chemotherapeutic-induced neuropathy, and the Sig-1R agonist SA4503 could serve as a potential candidate for the treatment of chemotherapeutic-induced neuropathy. © 2015 Wiley Periodicals, Inc.

A NEW EMPIRICAL INVESTIGATION OF THE PLATINUM SPOT RETURNS

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Simone Kruse

2017-08-01

Full Text Available The global platinum market has been in downturn and unstable for five consecutive years, and thus market participants are demanding effective quantitative risk management tools. Since platinum is so widely used and serves as an important investment vehicle, the importance of risk management of platinum spot returns cannot be understated. In this paper, we take advantage of a very popular econometric model, the generalized autoregressive conditional heteroscedasticity (GARCH model, for platinum returns. We received two important findings by using the conventional GARCH models in explain daily platinum spot returns. First, it is crucial to introduce heavy-tailed distribution to explain conditional heavy tails; and second, the NRIG distribution performs better than the most widely-used heavy-tailed distribution, the Student’s t distribution.

Aberrant DNA damage response pathways may predict the outcome of platinum chemotherapy in ovarian cancer.

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Dimitra T Stefanou

Full Text Available Ovarian carcinoma (OC is the most lethal gynecological malignancy. Despite the advances in the treatment of OC with combinatorial regimens, including surgery and platinum-based chemotherapy, patients generally exhibit poor prognosis due to high chemotherapy resistance. Herein, we tested the hypothesis that DNA damage response (DDR pathways are involved in resistance of OC patients to platinum chemotherapy. Selected DDR signals were evaluated in two human ovarian carcinoma cell lines, one sensitive (A2780 and one resistant (A2780/C30 to platinum treatment as well as in peripheral blood mononuclear cells (PBMCs from OC patients, sensitive (n = 7 or resistant (n = 4 to subsequent chemotherapy. PBMCs from healthy volunteers (n = 9 were studied in parallel. DNA damage was evaluated by immunofluorescence γH2AX staining and comet assay. Higher levels of intrinsic DNA damage were found in A2780 than in A2780/C30 cells. Moreover, the intrinsic DNA damage levels were significantly higher in OC patients relative to healthy volunteers, as well as in platinum-sensitive patients relative to platinum-resistant ones (all P<0.05. Following carboplatin treatment, A2780 cells showed lower DNA repair efficiency than A2780/C30 cells. Also, following carboplatin treatment of PBMCs ex vivo, the DNA repair efficiency was significantly higher in healthy volunteers than in platinum-resistant patients and lowest in platinum-sensitive ones (t1/2 for loss of γH2AX foci: 2.7±0.5h, 8.8±1.9h and 15.4±3.2h, respectively; using comet assay, t1/2 of platinum-induced damage repair: 4.8±1.4h, 12.9±1.9h and 21.4±2.6h, respectively; all P<0.03. Additionally, the carboplatin-induced apoptosis rate was higher in A2780 than in A2780/C30 cells. In PBMCs, apoptosis rates were inversely correlated with DNA repair efficiencies of these cells, being significantly higher in platinum-sensitive than in platinum-resistant patients and lowest in healthy volunteers (all P<0.05. We conclude

Assessment of genetic integrity, splenic phagocytosis and cell death potential of (Z-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl amino-4-oxobut-2-enoic acid and its effect when combined with commercial chemotherapeutics

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Rodrigo Juliano Oliveira

2018-02-01

Full Text Available Abstract The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl amino-4-oxobut-2-enoic acid (IR-01 and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment.

Collective Behavior of Water on Platinum

Science.gov (United States)

Limmer, David; Willard, Adam; Chandler, David

2012-02-01

We present the results of molecular dynamics simulations of a interface between water and a platinum electrode. Using importance sampling techniques we probe a variety of collective phenomenon that emerge at the interface. We consider platinum electrodes with two different geometries and discuss how different behaviors result from a competition between geometrical frustration and favorable local interactions.

Study of gold-platinum and platinum-gold surface modification and its influence on hydrogen evolution and oxygen reduction

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BRANIMIR N. GRGUR

2005-02-01

Full Text Available Surface modification of the electrodes was conducted from sulfuric acid solutions containing the corresponding metal–chloride complexes using cyclic voltammetry. Comparing the charges of the hydrogen underpotential deposition region, and the corresponding oxide reduction regions, it is concluded that a platinum overlayer on gold forms 3D islands, while gold on platinum forms 2D islands. Foreign metals present in an amount of up to one monolayer exert an influence on the change in reaction rate with respect to both hydrogen evolution (HER and oxygen reduction (ORR reactions. Aplatinum overlayer on a gold substrate increases the activity forHER and for ORR, compared with pure gold. These results can be understood in terms of a simple model, in which the change in the H and OH binding energies are directly proportional to the shift of the d-bond center of the overlayer. On the contrary, a gold layer on platinum slightly decreases the activity for both reactions compared with pure platinum.

Telomeric Allelic Imbalance Indicates Defective DNA Repair and Sensitivity to DNA-Damaging Agents

DEFF Research Database (Denmark)

Birkbak, Nicolai J.; Wang, Zhigang C.; Kim, Ji-Young

2012-01-01

with triple-negative breast cancer (TNBC). In serous ovarian cancer treated with platinum-based chemotherapy, higher levels of NtAI forecast a better initial response. We found an inverse relationship between BRCA1 expression and NtAI in sporadic TNBC and serous ovarian cancers without BRCA1 or BRCA2 mutation...... of defective DNA repair in cell lines and tumors and correlated these signatures to platinum sensitivity. The number of subchromosomal regions with allelic imbalance extending to the telomere (NtAI) predicted cisplatin sensitivity in vitro and pathologic response to preoperative cisplatin treatment in patients...... also benefit from these agents. NtAI, a genomic measure of unfaithfully repaired DNA, may identify cancer patients likely to benefit from treatments targeting defective DNA repair. Cancer Discov; 2(4); 366–75. ©2012 AACR. This article is highlighted in the In This Issue feature, p. 288...

Potentiometric sulfite biosensor based on entrapment of sulfite oxidase in a polypyrrole film on a platinum electrode modified with platinum nanoparticles

International Nuclear Information System (INIS)

Adeloju, Samuel B.; Hussain, Shahid

2016-01-01

The surface of a platinum electrode has been modified with platinum nanoparticles (PtNPs) and the enzyme sulfite oxidase (SOx), was entrapped on its surface in an ultrathin polypyrrole (PPy) film. The PtNPs, with a diameter of 30-40 nm, were deposited on the Pt electrode by cycling the electrode potential 20 times from -200 to 200 mV at a sweep rate of 50 mV.s"-"1. Morphological evidence of the successful incorporation of SOx and the presence of PtNPs were obtained by scanning electron microscopy. Also, the electrochemical behavior of the PtNPs/PPy-SOx film was examined by cyclic voltammetry, chronopotentiometry, electrochemical impedance spectroscopy and potentiometry. Under optimized conditions, the biosensor achieved a sensitivity of 57.5 mV.decade"-"1, a linear response that extends from 0.75 to 65 μM of sulfite, a detection limit of 12.4 nM, and a response time of 3-5 s. The biosensor was successfully applied to the determination of sulfite in wine and beer samples. (author)

Evaluation of chemotherapeutic sequelae and quality of life in survivors of malignant sacrococcygeal teratoma

NARCIS (Netherlands)

Kremer, Marijke E B; Derikx, Joep P M; Kremer, Leontien C M; van Baren, Robertine; Heij, Hugo A.; Wijnen, Marc H W A; Wijnen, René M H; van der Zee, David C.; van Heurn, L. W Ernest

2016-01-01

Purpose: The impact of chemotherapeutic sequelae on long-term quality of life (QoL) for survivors of malignant sacrococcygeal teratoma (SCT) is unknown. The incidence of chemotherapeutic toxicity in patients treated for malignant SCT and possible effects on the QoL were analyzed. Methods:

Optimising the treatment of the partially platinum-sensitive relapsed ovarian cancer patient

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Nicoletta Colombo

2014-12-01

Full Text Available The choice of second-line chemotherapy in patients with recurrent ovarian cancer (ROC is complex, with several factors to be considered, the most important of which is the length of the platinum-free treatment interval (PFI. Recently ROC patients have been further stratified into platinum sensitive (PS, partially platinum sensitive (PPS and platinum resistant (PR subgroups depending on the length of the PFI. Response to second-line therapy, progression-free survival (PFS and overall survival (OS are linked to the PFI, all of them improving as the PFI increases. Consequently, there is increasing interest in PFI extension strategies with platinum-free therapeutic options. Such strategies are currently being studied in patients with partially platinum-sensitive disease (PFI 6-12 months, as the treatment of these patients remains clinically challenging. A non-platinum option, trabectedin + pegylated liposomal doxorubicin (PLD combination, has been evaluated in ROC patients in the pivotal phase III OVA-301 study. The OVA-301 study differed from previous trials in the same setting as it included only patients who were not expected to benefit from or who were ineligible for or who were unwilling to receive re-treatment with platinum-based chemotherapy, including those with PPS and PR disease. Subset analysis of patients with PPS disease in OVA-301 showed that the trabectedin + PLD combination significantly improved PFS compared with PLD alone; median PFS 7.4 versus 5.5 months, p=0.0152. Final survival data from the same subset of patients, showed that trabectedin + PLD also achieved a significant 36% decrease in the risk of death compared with PLD alone (HR=0.64; 95% CI, 0.47–0.88; p=0.0027. Median overall survival (OS was 22.4 months in the trabectedin + PLD arm versus 16.4 months in the PLD arm. This represents a statistically significant 6-month improvement in median OS in patients treated with trabectedin + PLD compared to those treated with PLD

N-acetylaspartate (NAA) induces neuronal differentiation of SH-SY5Y neuroblastoma cell line and sensitizes it to chemotherapeutic agents.

Science.gov (United States)

Mazzoccoli, Carmela; Ruggieri, Vitalba; Tataranni, Tiziana; Agriesti, Francesca; Laurenzana, Ilaria; Fratello, Angelo; Capitanio, Nazzareno; Piccoli, Claudia

2016-05-03

Neuroblastoma is the most commonly extra-cranial solid tumor of childhood frequently diagnosed. The nervous system-specific metabolite N-acetylaspartate (NAA) is synthesized from aspartate and acetyl-CoA in neurons, it is among the most abundant metabolites present in the central nervous system (CNS) and appears to be involved in many CNS disorders. The functional significance of the high NAA concentration in the brain remains uncertain, but it confers to NAA a unique clinical significance exploited in magnetic resonance spectroscopy. In the current study, we show that treatment of SH-SY5Y neuroblastoma-derived cell line with sub-cytotoxic physiological concentrations of NAA inhibits cell growth. This effect is partly due to enhanced apoptosis, shown by decrease of the anti-apoptotic factors survivin and Bcl-xL, and partly to arrest of the cell-cycle progression, linked to enhanced expression of the cyclin-inhibitors p53, p21Cip1/Waf1 and p27Kip1. Moreover, NAA-treated SH-SY5Y cells exhibited morphological changes accompanied with increase of the neurogenic markers TH and MAP2 and down-regulation of the pluripotency markers OCT4 and CXCR4/CD184. Finally, NAA-pre-treated SH-SY5Y cells resulted more sensitive to the cytotoxic effect of the chemotherapeutic drugs Cisplatin and 5-fluorouracil.To our knowledge, this is the first study demonstrating the neuronal differentiating effects of NAA in neuroblastoma cells. NAA may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment.

Three essays in agent-based macroeconomics

OpenAIRE

Canzian, Giulia

2009-01-01

The dissertation is aimed at offering an insight into the agent-based methodology and its possible application to the macroeconomic analysis. Relying on this methodology, I deal with three different issues concerning heterogeneity of economic agents, bounded rationality and interaction. Specifically, the first chapter is devoted to describe the distinctive characteristics of agent-based economics and its advantages-disadvantages. In the second chapter I propose a credit market framework c...

Pemetrexed With Platinum Combination as a Backbone for Targeted Therapy in Non-Small-Cell Lung Cancer.

Science.gov (United States)

Stinchcombe, Thomas E; Borghaei, Hossein; Barker, Scott S; Treat, Joseph Anthony; Obasaju, Coleman

2016-01-01

Standard platinum-based chemotherapy combinations for advanced non-small-cell lung cancer (NSCLC) have reached a plateau in terms of the survival benefit they offer for patients. In addition, the emerging clinical trend of tailored treatment based on patient characteristics has led to the development of therapeutic strategies that target specific cancer-related molecular pathways, including epidermal growth factor receptor (EGFR), angiogenesis, and anaplastic lymphoma kinase inhibitors. Current research is focused on combining targeted therapy with platinum-based chemotherapy in an endeavor to achieve an additional benefit in specific patient populations. Currently, pemetrexed is indicated for use in the first-line, maintenance, and second-line settings for the treatment of nonsquamous NSCLC. The combination of pemetrexed and cisplatin is well tolerated and is the approved standard first-line therapy. Thus, the pemetrexed-platinum backbone provides an attractive option for combination with targeted therapies. This review aims to summarize the current knowledge and future prospects of the use of pemetrexed-platinum as a backbone for combination with targeted therapies for NSCLC. Copyright © 2016 Elsevier Inc. All rights reserved.

Recovery of Platinum from Dilute Chloride Media Using Biosorbents

Science.gov (United States)

Zeytuncu, B.; Morcali, M. H.; Yucel, O.

Pistachio nut shells and Rice husk, a biomass residue, were investigated as adsorbents for the platinum uptake from synthetically prepared dilute chloroplatinic acid solutions. The effects of the different uptake parameters on platinum uptake (%) were studied in detail on a batch sorption. Before the pistachio nut shell material was activated, platinum uptake (%) was poor compared with rice husk. However, after the pistachio nut shell material was activated at 1000°C under an argon atmosphere, the platinum uptake (%) increased two-fold. The pistachio nut shell (inactivated and activated) and rice husk were characterized by Attenuated Total Reflection-Fourier transform infrared spectroscopy (ATR-FTIR).

Bio-inspired routes for synthesizing efficient nanoscale platinum electrocatalysts

Energy Technology Data Exchange (ETDEWEB)

Cha, Jennifer N. [Univ. of California, San Diego, CA (United States); Wang, Joseph [Univ. of California, San Diego, CA (United States)

2014-08-31

The overall objective of the proposed research is to use fundamental advances in bionanotechnology to design powerful platinum nanocrystal electrocatalysts for fuel cell applications. The new economically-viable, environmentally-friendly, bottom-up biochemical synthetic strategy will produce platinum nanocrystals with tailored size, shape and crystal orientation, hence leading to a maximum electrochemical reactivity. There are five specific aims to the proposed bio-inspired strategy for synthesizing efficient electrocatalytic platinum nanocrystals: (1) isolate peptides that both selectively bind particular crystal faces of platinum and promote the nucleation and growth of particular nanocrystal morphologies, (2) pattern nanoscale 2-dimensional arrays of platinum nucleating peptides from DNA scaffolds, (3) investigate the combined use of substrate patterned peptides and soluble peptides on nanocrystal morphology and growth (4) synthesize platinum crystals on planar and large-area carbon electrode supports, and (5) perform detailed characterization of the electrocatalytic behavior as a function of catalyst size, shape and morphology. Project Description and Impact: This bio-inspired collaborative research effort will address key challenges in designing powerful electrocatalysts for fuel cell applications by employing nucleic acid scaffolds in combination with peptides to perform specific, environmentally-friendly, simultaneous bottom-up biochemical synthesis and patterned assembly of highly uniform and efficient platinum nanocrystal catalysts. Bulk synthesis of nanoparticles usually produces a range of sizes, accessible catalytic sites, crystal morphologies, and orientations, all of which lead to inconsistent catalytic activities. In contrast, biological systems routinely demonstrate exquisite control over inorganic syntheses at neutral pH and ambient temperature and pressures. Because the orientation and arrangement of the templating biomolecules can be precisely

Chemotherapeutic drug delivery by tumoral extracellular matrix targeting

NARCIS (Netherlands)

Raavé , R.; Kuppevelt, T.H. van; Daamen, W.F.

2018-01-01

Systemic chemotherapy is a primary strategy in the treatment of cancer, but comes with a number of limitations such as toxicity and unfavorable biodistribution. To overcome these issues, numerous targeting systems for specific delivery of chemotherapeutics to tumor cells have been designed and

Modelling and sensitivity analysis of urinary platinum excretion in anticancer chemotherapy for the recovery of platinum

DEFF Research Database (Denmark)

Folens, Karel; Mortier, Séverine Thérèse F C; Baeten, Janis

2016-01-01

Platinum (Pt) based antineoplastics are important in cancer therapy. To date the Pt which is urinary excreted by the patients ends up in wastewater. This is disadvantageous from both an economic as from an ecological point of view because Pt is a valuable material and the excretion products...... are toxic for aquatic organisms. Therefore, efforts should be made to recover the Pt. The urinary excretion of Pt from two antineoplastics are taken under consideration, i.e. cisplatin and carboplatin. Using these reference compounds, a scenario analysis based on administration statistics from Ghent...

Structures of 38-atom gold-platinum nanoalloy clusters

Energy Technology Data Exchange (ETDEWEB)

Ong, Yee Pin; Yoon, Tiem Leong [School of Physics, Universiti Sains Malaysia, 11800 USM, Penang (Malaysia); Lim, Thong Leng [Faculty of Engineering and Technology, Multimedia University, Melaka Campus, 75450 Melaka (Malaysia)

2015-04-24

Bimetallic nanoclusters, such as gold-platinum nanoclusters, are nanomaterials promising wide range of applications. We perform a numerical study of 38-atom gold-platinum nanoalloy clusters, Au{sub n}Pt{sub 38−n} (0 ≤ n ≤ 38), to elucidate the geometrical structures of these clusters. The lowest-energy structures of these bimetallic nanoclusters at the semi-empirical level are obtained via a global-minimum search algorithm known as parallel tempering multi-canonical basin hopping plus genetic algorithm (PTMBHGA), in which empirical Gupta many-body potential is used to describe the inter-atomic interactions among the constituent atoms. The structures of gold-platinum nanoalloy clusters are predicted to be core-shell segregated nanoclusters. Gold atoms are observed to preferentially occupy the surface of the clusters, while platinum atoms tend to occupy the core due to the slightly smaller atomic radius of platinum as compared to gold’s. The evolution of the geometrical structure of 38-atom Au-Pt clusters displays striking similarity with that of 38-atom Au-Cu nanoalloy clusters as reported in the literature.

The impact of whole human blood on the kinetic inertness of platinum(iv) prodrugs - an HPLC-ICP-MS study.

Science.gov (United States)

Theiner, Sarah; Grabarics, Márkó; Galvez, Luis; Varbanov, Hristo P; Sommerfeld, Nadine S; Galanski, Markus; Keppler, Bernhard K; Koellensperger, Gunda

2018-04-17

The potential advantage of platinum(iv) complexes as alternatives to classical platinum(ii)-based drugs relies on their kinetic stability in the body before reaching the tumor site and on their activation by reduction inside cancer cells. In this study, an analytical workflow has been developed to investigate the reductive biotransformation and kinetic inertness of platinum(iv) prodrugs comprising different ligand coordination spheres (respectively, lipophilicity and redox behavior) in whole human blood. The distribution of platinum(iv) complexes in blood pellets and plasma was determined by inductively coupled plasma-mass spectrometry (ICP-MS) after microwave digestion. An analytical approach based on reversed-phase (RP)-ICP-MS was used to monitor the parent compound and the formation of metabolites using two different extraction procedures. The ligand coordination sphere of the platinum(iv) complexes had a significant impact on their accumulation in red blood cells and on their degree of kinetic inertness in whole human blood. The most lipophilic platinum(iv) compound featuring equatorial chlorido ligands showed a pronounced penetration into blood cells and a rapid reductive biotransformation. In contrast, the more hydrophilic platinum(iv) complexes with a carboplatin- and oxaliplatin-core exerted kinetic inertness on a pharmacologically relevant time scale with notable amounts of the compound accumulated in the plasma fraction.

The predictive value of 53BP1 and BRCA1 mRNA expression in advanced non-small-cell lung cancer patients treated with first-line platinum-based chemotherapy

Science.gov (United States)

Bonanno, Laura; Costa, Carlota; Majem, Margarita; Sanchez, Jose Javier; Gimenez-Capitan, Ana; Rodriguez, Ignacio; Vergenegre, Alain; Massuti, Bartomeu; Favaretto, Adolfo; Rugge, Massimo; Pallares, Cinta; Taron, Miquel; Rosell, Rafael

2013-01-01

Platinum-based chemotherapy is the standard first-line treatment for non-oncogene-addicted non-small cell lung cancers (NSCLCs) and the analysis of multiple DNA repair genes could improve current models for predicting chemosensitivity. We investigated the potential predictive role of components of the 53BP1 pathway in conjunction with BRCA1. The mRNA expression of BRCA1, MDC1, CASPASE3, UBC13, RNF8, 53BP1, PIAS4, UBC9 and MMSET was analyzed by real-time PCR in 115 advanced NSCLC patients treated with first-line platinum-based chemotherapy. Patients expressing low levels of both BRCA1 and 53BP1 obtained a median progression-free survival of 10.3 months and overall survival of 19.3 months, while among those with low BRCA1 and high 53BP1 progression-free survival was 5.9 months (P <0.0001) and overall survival was 8.2 months (P=0.001). The expression of 53BP1 refines BRCA1-based predictive modeling to identify patients most likely to benefit from platinum-based chemotherapy. PMID:24197907

Nanofiber-deposited porous platinum enables glucose fuel cell anodes with high current density in body fluids

Science.gov (United States)

Frei, Maxi; Erben, Johannes; Martin, Julian; Zengerle, Roland; Kerzenmacher, Sven

2017-09-01

The poisoning of platinum anodes by body-fluid constituents such as amino acids is currently the main hurdle preventing the application of abiotic glucose fuel cells as battery-independent power supply for medical implants. We present a novel anode material that enables continuous operation of glucose oxidation anodes in horse serum for at least 30 days at a current density of (7.2 ± 1.9) μA cm-2. The fabrication process is based on the electro-deposition of highly porous platinum onto a 3-dimensional carbon nanofiber support, leading to approximately 2-fold increased electrode roughness factors (up to 16500 ± 2300). The material's superior performance is not only related to its high specific surface area, but also to an improved catalytic activity and/or poisoning resistance. Presumably, this results from the micro- and nanostructure of the platinum deposits. This represents a major step forward in the development of implantable glucose fuel cells based on long-term stable platinum electrodes.

[Pt(O,O'-acac)(γ-acac)(DMS)] versus cisplatin: apoptotic effects in B50 neuroblastoma cells.

Science.gov (United States)

Grimaldi, Maddalena; Santin, Giada; Insolia, Violetta; Dal Bo, Veronica; Piccolini, Valeria Maria; Veneroni, Paola; Barni, Sergio; Verri, Manuela; De Pascali, Sandra Angelica; Fanizzi, Francesco Paolo; Bernocchi, Graziella; Bottone, Maria Grazia

2016-05-01

Cisplatin is one of the most active chemotherapeutic agents used in the treatment of childhood and adult malignancies. Cisplatin induces cell death through different pathways. Despite its effectiveness, the continued clinical use of cisplatin is limited by onset of severe side effects (nephrotoxicity, ototoxicity and neurotoxicity) and drug resistance. Therefore, one of the main experimental oncology purpose is related to the search for new platinum-based drugs to create different types of adducts or more specific and effective subcellular targets. Thus, [Pt(O,O'-acac)(γ-acac)(DMS)], which reacts preferentially with protein thiols or thioether, was synthesized. In our research, different approaches were used to compare cisplatin and [Pt(O,O'-acac)(γ-acac)(DMS)] effects in B50 rat neuroblastoma cells. Our results, using immunocytochemical, cytometric and morphological techniques, showed that these compounds exert a cytostatic action and activate apoptosis with different pathways. Long-term effects demonstrated that [Pt(O,O'-acac)(γ-acac)(DMS)] exerts cytotoxic effects in neuronal B50 cell line not inducing drug resistance. Analysis was performed both to compare the ability of these platinum compounds to induce cell death and to investigate the intracellular mechanisms at the basis of their cytotoxicity.

Analytical determination of plutonium in the presence of complexing agents

International Nuclear Information System (INIS)

Nebel', D.

1975-01-01

The complexing of Pu(4) and Pu(6) with citrate and lactate were studied to establish possibilities which are provided by the complexing for analytical determination of plutonium in a solution. Plutonium in the sample analyzed is preliminarily reduced up to trivalent state. Then trivalent plutonium is oxidized up to tetravalent on the platinum electrode at +1.05 V. To avoid further oxidation complexing agents are added. The value of pH=2-4 is maintained to stabilize the oxidation degree. If hexavalent plutonium should be obtained, the oxidation is performed at the voltage of +1.5 V in the absence of complexing agents. Based on a detailed study of absorption spectra of plutonium complexes of various oxidation degrees it is stated that the most suitable for analytical purposes is the oxidation degree of Pu=4

High performance platinum single atom electrocatalyst for oxygen reduction reaction

Science.gov (United States)

Liu, Jing; Jiao, Menggai; Lu, Lanlu; Barkholtz, Heather M.; Li, Yuping; Wang, Ying; Jiang, Luhua; Wu, Zhijian; Liu, Di-Jia; Zhuang, Lin; Ma, Chao; Zeng, Jie; Zhang, Bingsen; Su, Dangsheng; Song, Ping; Xing, Wei; Xu, Weilin; Wang, Ying; Jiang, Zheng; Sun, Gongquan

2017-07-01

For the large-scale sustainable implementation of polymer electrolyte membrane fuel cells in vehicles, high-performance electrocatalysts with low platinum consumption are desirable for use as cathode material during the oxygen reduction reaction in fuel cells. Here we report a carbon black-supported cost-effective, efficient and durable platinum single-atom electrocatalyst with carbon monoxide/methanol tolerance for the cathodic oxygen reduction reaction. The acidic single-cell with such a catalyst as cathode delivers high performance, with power density up to 680 mW cm-2 at 80 °C with a low platinum loading of 0.09 mgPt cm-2, corresponding to a platinum utilization of 0.13 gPt kW-1 in the fuel cell. Good fuel cell durability is also observed. Theoretical calculations reveal that the main effective sites on such platinum single-atom electrocatalysts are single-pyridinic-nitrogen-atom-anchored single-platinum-atom centres, which are tolerant to carbon monoxide/methanol, but highly active for the oxygen reduction reaction.

Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives

DEFF Research Database (Denmark)

Ewertz, Marianne; Qvortrup, Camilla; Eckhoff, Lise

2015-01-01

BACKGROUND: Chemotherapy with taxanes and platinum compounds has resulted in substantial survival benefits both in adjuvant and metastatic settings. However, as a side effect, such chemotherapy may cause peripheral neuropathy (CIPN) which may result in discontinuation of treatment...... or shortly after the infusion triggered by exposure to cold. Risks factors for CIPN include preexisting neuropathy, either from treatment with other neurotoxic agents, or from comorbid conditions. The incidence of CIPN is related to dose per cycle, cumulative dose, and duration of infusion. While cisplatin......-induced neuropathy is irreversible, CIPN induced by taxanes may persist for several years in about 30% of patients. Evidence from the literature is suggestive that CIPN is likely to be negatively associated with QoL. No agents have been identified to be recommended for the prevention of CIPN. For treatment of CIPN...

Platinum uptake from chloride solutions using biosorbents

Directory of Open Access Journals (Sweden)

Mehmet Hakan Morcali

2013-04-01

Full Text Available Present work investigates platinum uptake from synthetically prepared, dilute platinum-bearing solutions using biomass residues, i.e. pistachio nut shell and rice husk, which are abundant in Turkey, and provides a comparison between these two biosorbents. Effects of the different uptake parameters, sorbent dosage, contact time, temperature and pH of solution on platinum uptake (% were studied in detail on a batch sorption. Before the pistachio nut shell was activated, platinum uptake (% was poor compared to the rice husk. However, after the pistachio nut shell was activated at 1000 °C under an argon atmosphere, the platinum uptake (% increased two-fold. The pistachio nut shell (original and activated and rice husk were shown to be better than commercially available activated carbon in terms of adsorption capacity. These two sorbents have also been characterized by FTIR and SEM. Adsorption equilibrium data best complied with the Langmuir isotherm model. Maximum adsorption capacities, Qmax, at 25 °C were found to be 38.31 and 42.02 mg.g- 1for the activated pistachio nut shell and rice husk, respectively. Thermodynamic calculations using the measured ∆H°, ∆S° and ∆G° values indicate that the uptake process was spontaneous and endothermic. The experimental data were shown to be fit the pseudo-second-order kinetic model.

Delivery of chemotherapeutic drugs in tumour cell-derived microparticles.

Science.gov (United States)

Tang, Ke; Zhang, Yi; Zhang, Huafeng; Xu, Pingwei; Liu, Jing; Ma, Jingwei; Lv, Meng; Li, Dapeng; Katirai, Foad; Shen, Guan-Xin; Zhang, Guimei; Feng, Zuo-Hua; Ye, Duyun; Huang, Bo

2012-01-01

Cellular microparticles are vesicular plasma membrane fragments with a diameter of 100-1,000 nanometres that are shed by cells in response to various physiological and artificial stimuli. Here we demonstrate that tumour cell-derived microparticles can be used as vectors to deliver chemotherapeutic drugs. We show that tumour cells incubated with chemotherapeutic drugs package these drugs into microparticles, which can be collected and used to effectively kill tumour cells in murine tumour models without typical side effects. We describe several mechanisms involved in this process, including uptake of drug-containing microparticles by tumour cells, synthesis of additional drug-packaging microparticles by these cells that contribute to the cytotoxic effect and the inhibition of drug efflux from tumour cells. This study highlights a novel drug delivery strategy with potential clinical application.

Graphite-supported platinum catalysts: Effects of gas and aqueous phase treatments

Energy Technology Data Exchange (ETDEWEB)

Vleeming, J.H.; Kuster, B.F.M.; Marin, G.B. [Eindhoven Univ. of Technology (Netherlands)] [and others

1997-03-01

The effects on the platinum particle diameter and the available platinum surface area of a graphite-supported platinum catalyst resulting from pretreatments and from performing a selective oxidation reaction are investigated. In the gas phase considerable catalyst sintering occurs only in the presence of oxygen at 773 K due to extensive carbon burn-off, whereas in an aqueous phase platinum particle growth is limited upon oxidative treatment. A hydrogen treatment in aqueous phase at 363 K causes platinum particle growth, aggregate formation, and covering of metal sites. These phenomena become more important with increasing pH. Platinum particle growth and aggregate formation are attributed to platinum particle rather than platinum adatom mobility and is caused by the destruction of the oxygen-containing surface groups on the graphite support, which serve as anchorage sites for the platinum particles. Site covering is caused by products originating from the graphite support, which are formed as a result of the reductive treatments. When performing the aqueous phase oxidation of methyl {alpha}-D-glucopyranoside at 323 K and a pH of 9, catalyst modifications are small under oxidative conditions. Exposure of the catalyst for several hours to methyl {alpha}-D-glucopyranoside under the same conditions but in the absence of oxygen causes site covering. 50 refs., 9 figs., 1 tab.

Fresh garlic extract inhibits Staphylococcus aureus biofilm formation under chemopreventive and chemotherapeutic conditions

Directory of Open Access Journals (Sweden)

Panan Ratthawongjirakul

2016-08-01

Full Text Available Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA are the leading aetiological pathogens of nosocomial infections worldwide. These bacteria form biofilms on both biotic and abiotic surfaces causing biofilm-associated infections. Within the biofilm, these bacteria might develop persistent and antimicrobial resistant characteristics resulting in chronic infections and treatment failures. Garlic exhibits broad pharmaceutical properties and inhibitory activities against S. aureus. We investigated the effects of aqueous fresh garlic extract on biofilm formation in S. aureus ATCC25923 and MRSA strains under chemopreventive and chemotherapeutic conditions. The viable bacteria and biofilm levels were quantified through colony count and crystal violet staining, respectively. The use of fresh garlic extract under both conditions significantly inhibited biofilm formation in S. aureus strains ATCC25923 and MRSA. Garlic could be developed as either a prophylactic or therapeutic agent to manage S. aureus biofilm-associated infections.

Room temperature synthesis of colloidal platinum nanoparticles

Indian Academy of Sciences (India)

Unknown

platinum cation used. ... Particle size increased with low reagent concentration. ... 2,100) was added separately to the starting solution. Argon gas was bubbled in the solution for 20 min. Later, reduction of platinum ions was carried out by bubbling hydrogen gas ... plex to aquate (Cl– → H2O ligand exchange). ... copper grid.

Paclitaxel-loaded iron platinum stealth immunomicelles are potent MRI imaging agents that prevent prostate cancer growth in a PSMA-dependent manner

Directory of Open Access Journals (Sweden)

Taylor RM

2012-08-01

Full Text Available Robert M Taylor,1,2 Laurel O Sillerud1,31Department of Biochemistry and Molecular Biology, 2New Mexico Cancer Nanoscience and Microsystems Training Center, 3UNM Cancer Center, University of New Mexico, Albuquerque, NM, USABackground and methods: Problems with the clinical management of prostate cancer include the lack of both specific detection and efficient therapeutic intervention. We report the encapsulation of superparamagnetic iron platinum nanoparticles (SIPPs and paclitaxel in a mixture of polyethyleneglycolated, fluorescent, and biotin-functionalized phospholipids to create multifunctional SIPP-PTX micelles (SPMs that were conjugated to an antibody against prostate-specific membrane antigen (PSMA for the specific targeting, magnetic resonance imaging (MRI, and treatment of human prostate cancer xenografts in mice.Results: SPMs were 45.4 ± 24.9 nm in diameter and composed of 160.7 ± 22.9 µg/mL iron, 247.0 ± 33.4 µg/mL platinum, and 702.6 ± 206.0 µg/mL paclitaxel. Drug release measurements showed that, at 37°C, half of the paclitaxel was released in 30.2 hours in serum and two times faster in saline. Binding assays suggested that PSMA-targeted SPMs specifically bound to C4-2 human prostate cancer cells in vitro and released paclitaxel into the cells. In vitro, paclitaxel was 2.2 and 1.6 times more cytotoxic than SPMs to C4-2 cells at 24 and 48 hours of incubation, respectively. After 72 hours of incubation, paclitaxel and SPMs were equally cytotoxic. SPMs had MRI transverse relaxivities of 389 ± 15.5 Hz/mM iron, and SIPP micelles with and without drug caused MRI contrast enhancement in vivo.Conclusion: Only PSMA-targeted SPMs and paclitaxel significantly prevented growth of C4-2 prostate cancer xenografts in nude mice. Furthermore, mice injected with PSMA-targeted SPMs showed significantly more paclitaxel and platinum in tumors, compared with nontargeted SPM-injected and paclitaxel-injected mice.Keywords: iron platinum, MRI

Point defects in platinum

International Nuclear Information System (INIS)

Piercy, G.R.

1960-01-01

An investigation was made of the mobility and types of point defect introduced in platinum by deformation in liquid nitrogen, quenching into water from 1600 o C, or reactor irradiation at 50 o C. In all cases the activation energy for motion of the defect was determined from measurements of electrical resistivity. Measurements of density, hardness, and x-ray line broadening were also made there applicable. These experiments indicated that the principal defects remaining in platinum after irradiation were single vacant lattice sites and after quenching were pairs of vacant lattice sites. Those present after deformation In liquid nitrogen were single vacant lattice sites and another type of defect, perhaps interstitial atoms. (author)

Platinum uptake by the freshwater isopod Asellus Aquaticus in urban rivers

Energy Technology Data Exchange (ETDEWEB)

Rauch, S.; Morrison, G.M. [Department of Sanitary Engineering, Chalmers University of Technology, S-412 96 Goeteborg (Sweden)

1999-09-01

Platinum has been increasing in the environment as a result of emissions from catalytic converters. The platinum emitted is principally located in the vicinity of roads but might be transported to urban rivers through highway and urban run-off water. Platinum concentrations in the freshwater isopod Asellus aquaticus were measured for two urban rivers and a stormwater detention pond. Concentrations ranged from 0.04 to 12.4 {mu}g g{sup -1} for direct analysis and from 0.16 to 4.5 {mu}g g{sup -1} after depuration. Analyses of water, pore water and sediments indicate that platinum in urban rivers is mostly found in the sediments and these provide the major contribution of platinum to Asellus aquaticus. Exposure experiments showed the importance of platinum speciation for uptake.

Synthesis of platinum nanowheels using a bicellar template.

Science.gov (United States)

Song, Yujiang; Dorin, Rachel M; Garcia, Robert M; Jiang, Ying-Bing; Wang, Haorong; Li, Peng; Qiu, Yan; van Swol, Frank; Miller, James E; Shelnutt, John A

2008-09-24

Disk-like surfactant bicelles provide a unique meso-structured reaction environment for templating the wet-chemical reduction of platinum(II) salt by ascorbic acid to produce platinum nanowheels. The Pt wheels are 496 +/-55 nm in diameter and possess thickened centers and radial dendritic nanosheets (about 2-nm in thickness) culminating in flared dendritic rims. The structural features of the platinum wheels arise from confined growth of platinum within the bilayer that is also limited at edges of the bicelles. The size of CTAB/FC7 bicelles is observed to evolve with the addition of Pt(II) complex and ascorbic acid. Synthetic control is demonstrated by varying the reaction parameters including metal salt concentration, temperature, and total surfactant concentration. This study opens up opportunities for the use of other inhomogeneous soft templates for synthesizing metals, metal alloys, and possibly semiconductors with complex nanostructures.

Synthesis and In Vitro Performance of Polypyrrole-Coated Iron-Platinum Nanoparticles for Photothermal Therapy and Photoacoustic Imaging

Science.gov (United States)

Phan, Thi Tuong Vy; Bui, Nhat Quang; Moorthy, Madhappan Santha; Lee, Kang Dae; Oh, Junghwan

2017-10-01

Multifunctional nano-platform for the combination of photo-based therapy and photoacoustic imaging (PAI) for cancer treatment has recently attracted much attention to nanotechnology development. In this study, we developed iron-platinum nanoparticles (FePt NPs) with the polypyrrole (PPy) coating as novel agents for combined photothermal therapy (PTT) and PAI. The obtained PPy-coated FePt NPs (FePt@PPy NPs) showed excellent biocompatibility, photothermal stability, and high near-infrared (NIR) absorbance for the combination of PTT and PAI. In vitro investigation experimentally demonstrated the effectiveness of FePt@PPy NPs in killing cancer cells with NIR laser irradiation. Moreover, the phantom test of PAI used in conjunction with FePt@PPy NPs showed a strong photoacoustic signal. Thus, the novel FePt@PPy NPs could be considered as promising multifunctional nanoparticles for further applications of photo-based diagnosis and treatment.

An Emotional Agent Model Based on Granular Computing

Directory of Open Access Journals (Sweden)

Jun Hu

2012-01-01

Full Text Available Affective computing has a very important significance for fulfilling intelligent information processing and harmonious communication between human being and computers. A new model for emotional agent is proposed in this paper to make agent have the ability of handling emotions, based on the granular computing theory and the traditional BDI agent model. Firstly, a new emotion knowledge base based on granular computing for emotion expression is presented in the model. Secondly, a new emotional reasoning algorithm based on granular computing is proposed. Thirdly, a new emotional agent model based on granular computing is presented. Finally, based on the model, an emotional agent for patient assistant in hospital is realized, experiment results show that it is efficient to handle simple emotions.

Graphene–platinum nanocomposite as a sensitive and selective voltammetric sensor for trace level arsenic quantification

Directory of Open Access Journals (Sweden)

R. Kempegowda

2014-01-01

Full Text Available A simple protocol for the chemical modification of graphene with platinum nanoparticles and its subsequent electroanalytical application toward sensitive and selective determination of arsenic has been described. Chemical modification was carried out by the simultaneous and sequential chemical reduction of graphene oxide and hexachloroplatinic acid in the presence of ethylene glycol as a mild reducing agent. The synthesized graphene–platinum nanocomposite (Gr–nPt has been characterized through infrared spectroscopy, x-ray diffraction study, field emission scanning electron microscopy and cyclic voltammetry (CV techniques. CV and square-wave anodic stripping voltammetry have been used to quantify arsenic. The proposed nanostructure showed linearity in the concentration range 10–100 nM with a detection limit of 1.1 nM. The proposed sensor has been successfully applied to measure trace levels of arsenic present in natural sample matrices like borewell water, polluted lake water, agricultural soil, tomato and spinach leaves.

The role of interleukin-8 (IL-8) and IL-8 receptors in platinum response in high grade serous ovarian carcinoma.

Science.gov (United States)

Stronach, Euan A; Cunnea, Paula; Turner, Christina; Guney, Tankut; Aiyappa, Radhika; Jeyapalan, Senthuran; de Sousa, Camila H; Browne, Alacoque; Magdy, Nesreen; Studd, James B; Sriraksa, Ruethairat; Gabra, Hani; El-Bahrawy, Mona

2015-10-13

Platinum based drugs are the cornerstone of chemotherapy for ovarian cancer, however the development of chemoresistance hinders its success. IL-8 is involved in regulating several pro-survival pathways in cancer. We studied the expression of IL-8 and IL-8 receptors in platinum sensitive and resistant cell lines. Using qRT-PCR and immunohistochemistry, both platinum sensitive (PEA1, PEO14) and resistant (PEA2, PEO23) show increased expression of IL-8 and IL-8 receptors. IL-8RA shows nuclear and cytoplasmic expression, whilst IL-8RB is present solely in the cytoplasm. Knockdown of IL-8 increased sensitivity to cisplatin in platinum sensitive and reversed platinum resistance in resistant cell lines, decreased the expression of anti-apoptotic Bcl-2 and decreased inhibitory phosphorylation of pro-apoptotic Bad. IL-8 receptor antagonist treatment also enhanced platinum sensitivity. Nuclear localisation of IL-8RA was only detected in platinum resistant tumours. Inhibition of IL-8 signalling can enhance response in platinum sensitive and resistant disease. Nuclear IL-8RA may have potential as a biomarker of resistant disease.

Diffuse X-Ray Scattering from Several Platinum Chain Compounds

DEFF Research Database (Denmark)

Braude, A.; Lindegaard-Andersen, Asger; Carneiro, K.

1980-01-01

Values of the Fermi wavevector for several platinum based one-dimensional conductors were determined from diffuse X-ray scattering measurements. The values were compared with those expected from the chemical compositions. The importance of conclusive values of this parameter is stressed and the c...

Recent advances in nanoformulations for co-delivery of curcumin and chemotherapeutic drugs

Directory of Open Access Journals (Sweden)

Maryam Hashemi

2017-01-01

Full Text Available The application of chemotherapy in cancer treatment has been limited due to cause side effects such as toxicity against normal cells and drug resistance. In recent years, numerous studies have been focused on using natural products with chemotherapeutic drugs to enhance therapeutic efficiency and reduce cytotoxicity. On the other hand, encapsulation of drugs into nanoparticles (NPs can improve solubility of hydrophobic drug; circulation time in blood and the residence at the pathological site by enhance permeation and retention (EPR effect. It has been shown that curcumin (CUR has  wide range of pharmacological activities against many diseases such as cancer. CUR has been demonstrated to be a potent chemosensitizer that can induce additive or synergistic effects with chemotherapeutic drugs against different cancer cell lines.  Recently, various types of nanocarriers have been investigated for CUR.  In this review, different co-formulations containing Cur and chemotherapeutic drugs used in cancer therapy are discussed with emphasis on their pharmaceutical properties.

Plant-Derived Agents for Counteracting Cisplatin-Induced Nephrotoxicity

OpenAIRE

Ojha, Shreesh; Venkataraman, Balaji; Kurdi, Amani; Mahgoub, Eglal; Sadek, Bassem; Rajesh, Mohanraj

2016-01-01

Cisplatin (CSP) is a chemotherapeutic agent commonly used to treat a variety of malignancies. The major setback with CSP treatment is that its clinical efficacy is compromised by its induction of organ toxicity, particular to the kidneys and ears. Despite the significant strides that have been made in understanding the mechanisms underlying CSP-induced renal toxicity, advances in developing renoprotective strategies are still lacking. In addition, the renoprotective approaches described in th...

A Change to the Platinum Publications | Poster

Science.gov (United States)

Please be advised that the Poster will no longer publish the “Platinum Publications” series listing recent NCI at Frederick publications. All published research represents a valuable addition to the fight against cancer, AIDS, and infectious diseases—thus, the “Platinum Publications” did not adequately commend all of the important work done by NCI at Frederick researchers.

Innovative agents in cancer prevention.

Science.gov (United States)

Manson, Margaret M; Farmer, Peter B; Gescher, Andreas; Steward, William P

2005-01-01

There are many facets to cancer prevention: a good diet, weight control and physical activity, a healthy environment, avoidance of carcinogens such as those in tobacco smoke, and screening of populations at risk to allow early detection. But there is also the possibility of using drugs or naturally occurring compounds to prevent initiation of, or to suppress, tumour growth. Only a few such agents have been used to date in the clinic with any success, and these include non-steroidal anti-inflammatory drugs for colon, finasteride for prostate and tamoxifen or raloxifene for breast tumours. An ideal chemopreventive agent would restore normal growth control to a preneoplastic or cancerous cell population by modifying aberrant signalling pathways or inducing apoptosis (or both) in cells beyond repair. Characteristics for such an agent include selectivity for damaged or transformed cells, good bioavailability and more than one mechanism of action to foil redundancy or crosstalk in signalling pathways. As more research effort is being targeted towards this area, the distinction between chemotherapeutic and chemopreventive agents is blurring. Chemotherapeutic drugs are now being designed to target over- or under-active signalling molecules within cancer cells, a philosophy which is just as relevant in chemoprevention. Development of dietary agents is particularly attractive because of our long-standing exposure to them, their relative lack of toxicity, and encouraging indications from epidemiology. The carcinogenic process relies on the cell's ability to proliferate abnormally, evade apoptosis, induce angiogenesis and metastasise to distant sites. In vitro studies with a number of different diet-derived compounds suggest that there are molecules capable of modulating each of these aspects of tumour growth. However, on the negative side many of them have rather poor bioavailability. The challenge is to uncover their multiple mechanisms of action in order to predict their

Radiochemical neutron activation analysis of high pure palladium and platinum by ion exchange chromatography

International Nuclear Information System (INIS)

Sadikov, I.I.; Zinov'ev, V.G.; Sadikova, Z.O.; Salimov, M.I.

2006-01-01

volume was obtained by elution curve of the determined elements and distribution profile of the matrix elements. Chemical yields of determined elements were measured by 'entered - found' method. Chemical yields of Sn is 31.2%; Zn is 54.5%; Se is 74.%1, and for other elements it is more than 85 %. Based on the carried out researches the radiochemical neutron activation analysis techniques of a high pure palladium and platinum are developed. These techniques allow determination of more than 30 elements with detection limits 10 -5 -10 -9 % with S r 0.15-0.2. (author)

Dissolution of Platinum in Hydrochloric Acid Under Industrial-Scale Alternating Current Polarization

Science.gov (United States)

Myrzabekov, B. E.; Bayeshov, A. B.; Makhanbetov, A. B.; Mishra, B.; Baigenzhenov, O. S.

2018-02-01

The electrochemical behavior of platinum in a hydrochloric acid solution under polarization by an industrial-scale alternating current has been investigated. For the electrical dissolution of platinum, titanium is used as an auxiliary electrode, which increases the yield of platinum dissolution by 12.5 pct. The influence of the concentration of hydrochloric acid, the current densities of the platinum and titanium electrodes, and the temperature of the electrolyte on the efficiency of the process of dissolving platinum have all been studied.

Mechanooptic Regulation of Photoconduction in Functionalized Carbon Nanotubes Decorated with Platinum

Directory of Open Access Journals (Sweden)

C. Mercado-Zúñiga

2014-01-01

Full Text Available The observation of photoconduction and nonlinear optical absorption on functionalized multiwall carbon nanotubes decorated with platinum is reported. The samples were prepared by a chemical vapor deposition method. The electrical conductivity of the carbon nanotubes seems to be decreased by the functionalization process; but this property is strongly enhanced after the incorporation of platinum particles. Nonresonant photoconductive experiments at 532 nm and 445 nm wavelengths allow us to detect a selective participation of the platinum to the photoelectrical response. A mechanooptic effect based on Fresnel reflection was obtained through a photoconductive modulation induced by the rotation of a silica substrate where the samples were deposited as a thin film. A two-photon absorption process was identified as the main physical mechanism responsible for the nonlinear optical absorption. We consider that important changes in the nonlinear photon interactions with carbon nanotubes can be related to the population losses derived from phonons and the detuning of the frequency originated by functionalization.

Methods for Model-Based Reasoning within Agent-Based Ambient Intelligence Applications

NARCIS (Netherlands)

Bosse, T.; Both, F.; Gerritsen, C.; Hoogendoorn, M.; Treur, J.

2012-01-01

Within agent-based Ambient Intelligence applications agents react to humans based on information obtained by sensoring and their knowledge about human functioning. Appropriate types of reactions depend on the extent to which an agent understands the human and is able to interpret the available

Chemotherapeutic agents attenuate CXCL12-mediated migration of colon cancer cells by selecting for CXCR4-negative cells and increasing peptidase CD26

International Nuclear Information System (INIS)

Cutler, Murray J.; Lowthers, Erica L.; Richard, Cynthia L.; Hajducek, Dagmar M.; Spagnuolo, Paul A.; Blay, Jonathan

2015-01-01

Recurrence of colorectal cancer (CRC) may arise due to the persistence of drug-resistant and cancer-initiating cells that survive exposure to chemotherapy. Proteins responsible for this recurrence include the chemokine receptor CXCR4, which is known to enable CRC metastasis, as well as the cancer-initiating cell marker and peptidase CD26, which terminates activity of its chemokine CXCL12. We evaluated the expression and function of CXCR4 and CD26 in colon cancer cell lines and xenografts following treatment with common chemotherapies using radioligand binding, flow cytometry, immunofluorescence, and enzymatic assays. 5-Fluorouracil, oxaliplatin and SN-38 (the active metabolite of irinotecan), as well as cisplatin, methotrexate and vinblastine, each caused decreases in cell-surface CXCR4 and concomitant increases in CD26 on HT-29, T84, HRT-18, SW480 and SW620 CRC cell lines. Flow cytometry indicated that the decline in CXCR4 was associated with a significant loss of CXCR4+/CD26- cells. Elevations in CD26 were paralleled by increases in both the intrinsic dipeptidyl peptidase activity of CD26 as well as its capacity to bind extracellular adenosine deaminase. Orthotopic HT-29 xenografts treated with standard CRC chemotherapeutics 5-fluorouracil, irinotecan, or oxaliplatin showed dramatic increases in CD26 compared to untreated tumors. Consistent with the loss of CXCR4 and gain in CD26, migratory responses to exogenous CXCL12 were eliminated in cells pretreated with cytotoxic agents, although cells retained basal motility. Analysis of cancer-initiating cell CD44 and CD133 subsets revealed drug-dependent responses of CD26/CD44/CD133 populations, suggesting that the benefits of combining standard chemotherapies 5-fluoruracil and oxaliplatin may be derived from their complementary elimination of cell populations. Our results indicate that conventional anticancer agents may act to inhibit chemokine-mediated migration through eradication of CXCR4+ cells and attenuation of

A robust and rapid xenograft model to assess efficacy of chemotherapeutic agents for human acute myeloid leukemia

International Nuclear Information System (INIS)

Saland, E; Boutzen, H; Castellano, R; Pouyet, L; Griessinger, E; Larrue, C; Toni, F de; Scotland, S; David, M; Danet-Desnoyers, G; Vergez, F; Barreira, Y; Collette, Y; Récher, C; Sarry, J-E

2015-01-01

Relevant preclinical mouse models are crucial to screen new therapeutic agents for acute myeloid leukemia (AML). Current in vivo models based on the use of patient samples are not easy to establish and manipulate in the laboratory. Our objective was to develop robust xenograft models of human AML using well-characterized cell lines as a more accessible and faster alternative to those incorporating the use of patient-derived AML cells. Five widely used AML cell lines representing various AML subtypes were transplanted and expanded into highly immunodeficient non-obese diabetic/LtSz-severe combined immunodeficiency IL2Rγ c null mice (for example, cell line-derived xenografts). We show here that bone marrow sublethal conditioning with busulfan or irradiation has equal efficiency for the xenotransplantation of AML cell lines. Although higher number of injected AML cells did not change tumor engraftment in bone marrow and spleen, it significantly reduced the overall survival in mice for all tested AML cell lines. On the basis of AML cell characteristics, these models also exhibited a broad range of overall mouse survival, engraftment, tissue infiltration and aggressiveness. Thus, we have established a robust, rapid and straightforward in vivo model based on engraftment behavior of AML cell lines, all vital prerequisites for testing new therapeutic agents in preclinical studies

An Agent-Based Monetary Production Simulation Model

DEFF Research Database (Denmark)

Bruun, Charlotte

2006-01-01

An Agent-Based Simulation Model Programmed in Objective Borland Pascal. Program and source code is downloadable......An Agent-Based Simulation Model Programmed in Objective Borland Pascal. Program and source code is downloadable...

Story telling engine based on agent interaction

OpenAIRE

Porcel, Juan Carlos

2008-01-01

Comics have been used as a programming tool for agents, giving them instructions on how to act. In this thesis I do this in reverse, I use comics to describe the actions of agents already interacting with each other to create a storytelling engine that dynamically generate stories, based on the interaction of said agents. The model for the agent behaviours is based on the improvisational puppets model of Barbara Hayes-Roth. This model is chosen due to the nature of comics themselves. Comics ...

Preparation of platinum/iridium scanning probe microscopy tips

DEFF Research Database (Denmark)

Sørensen, Alexis Hammer; Hvid, U.; Mortensen, M.W.

1999-01-01

oxide layer. In order to explain the relatively high etching rates observed for the otherwise noble metal platinum we suggest that besides anodic corrosion of the platinum by the electrolyte containing chloride ions, a different etching mechanism causes a substantial increase of the etching rate...

New exploration methods for platinum and rhodium deposits poor in base-metal sulphides

DEFF Research Database (Denmark)

Ohnenstetter, M.; Johan, Z.; Cocherie, A.

1999-01-01

Platinum-group elements (PGE) are typically associated with mafic and ultramafic intrusive rocks and the main exploration targets are layers and zones rich in PGE-bearing sulphides. Some PGE occurences, however, are in sulphide-poor situations and this raises the possibility that PGE deposits may...

Peroxide bleaching agent effects on enamel surface microhardness, roughness and morphology Efeitos de agentes clareadores à base de peróxidos na microdureza, rugosidade e morfologia superficial do esmalte

Directory of Open Access Journals (Sweden)

Cristiane Franco Pinto

2004-12-01

Full Text Available The aim of this study was to evaluate the surface roughness, microhardness and morphology of human enamel exposed to six bleaching agents (at baseline and post-treatment. Human dental enamel samples were obtained from human third molars and randomly divided into seven groups (n = 11: control, Whiteness Perfect - 10% carbamide peroxide (10% CP, Colgate Platinum - 10% CP, Day White 2Z - 7.5% hydrogen peroxide (7.5% HP, Whiteness Super - 37% CP, Opalescence Quick - 35% CP and Whiteness HP - 35% HP. Bleaching agents were applied according to manufacturers' instructions. The control group remained not treated and stored in artificial saliva. Microhardness testing was performed with a Knoop indentor and surface roughness was analyzed with a profilometer. Morphologic observations were carried out with scanning electron microscopy (SEM. Results were statistically analyzed by two-way analysis of variance and Tukey's test (5%, and revealed a significant decrease in microhardness values and a significant increase in surface roughness post-bleaching. Changes in enamel morphology after bleaching were observed under SEM. It was concluded that bleaching agents can alter the microhardness, roughness and morphology of dental enamel surface.O objetivo deste estudo foi avaliar a rugosidade, microdureza e morfologia superficial do esmalte dental humano tratado com seis agentes clareadores (antes e depois do tratamento. Amostras de esmalte dental humano foram obtidas de terceiros molares e aleatoriamente distribuídas em sete grupos (n = 11: controle, Whiteness Perfect - peróxido de carbamida a 10% (PC 10%, Colgate Platinum - PC 10%, Day White 2Z - peróxido de hidrogênio a 7,5% (PH 7,5%, Whiteness Super - PC 37%, Opalescence Quick - PC 35% e Whiteness HP - PH 35%. Os agentes clareadores foram aplicados de acordo com as instruções dos fabricantes. O grupo controle permaneceu sem tratamento e armazenado em saliva artificial. O teste de microdureza foi realizado

A Secure Protocol Based on a Sedentary Agent for Mobile Agent Environments

OpenAIRE

Abdelmorhit E. Rhazi; Samuel Pierre; Hanifa Boucheneb

2007-01-01

The main challenge when deploying mobile agent environments pertains to security issues concerning mobile agents and their executive platform. This paper proposes a secure protocol which protects mobile agents against attacks from malicious hosts in these environments. Protection is based on the perfect cooperation of a sedentary agent running inside a trusted third host. Results show that the protocol detects several attacks, such as denial of service, incorrect execution and re-execution of...

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database.

Science.gov (United States)

Naganuma, Misa; Motooka, Yumi; Sasaoka, Sayaka; Hatahira, Haruna; Hasegawa, Shiori; Fukuda, Akiho; Nakao, Satoshi; Shimada, Kazuyo; Hirade, Koseki; Mori, Takayuki; Yoshimura, Tomoaki; Kato, Takeshi; Nakamura, Mitsuhiro

2018-01-01

Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database. We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence. We evaluated the time-to-onset profile of renal impairment and assessed the hazard type using Weibull shape parameter and used the applied association rule mining technique to discover undetected relationships such as possible risk factor. In total, 430,587 reports in the Japanese Adverse Drug Event Report database were analyzed. The reporting odds ratios (95% confidence interval) for renal impairment resulting from the use of cisplatin, oxaliplatin, carboplatin, and nedaplatin were 2.7 (2.5-3.0), 0.6 (0.5-0.7), 0.8 (0.7-1.0), and 1.3 (0.8-2.1), respectively. The lower limit of the reporting odds ratio (95% confidence interval) for cisplatin was >1. The median (lower-upper quartile) onset time of renal impairment following the use of platinum-based compounds was 6.0-8.0 days. The Weibull shape parameter β and 95% confidence interval upper limit of oxaliplatin were impairment during cisplatin use in real-world setting. The present findings demonstrate that the incidence of renal impairment following cisplatin use should be closely monitored when patients are hypertensive or diabetic, or when they are co-administered furosemide, loxoprofen, or pemetrexed. In addition, healthcare professionals should closely assess a patient's background prior to treatment.

Evolutionary game theory using agent-based methods.

Science.gov (United States)

Adami, Christoph; Schossau, Jory; Hintze, Arend

2016-12-01

Evolutionary game theory is a successful mathematical framework geared towards understanding the selective pressures that affect the evolution of the strategies of agents engaged in interactions with potential conflicts. While a mathematical treatment of the costs and benefits of decisions can predict the optimal strategy in simple settings, more realistic settings such as finite populations, non-vanishing mutations rates, stochastic decisions, communication between agents, and spatial interactions, require agent-based methods where each agent is modeled as an individual, carries its own genes that determine its decisions, and where the evolutionary outcome can only be ascertained by evolving the population of agents forward in time. While highlighting standard mathematical results, we compare those to agent-based methods that can go beyond the limitations of equations and simulate the complexity of heterogeneous populations and an ever-changing set of interactors. We conclude that agent-based methods can predict evolutionary outcomes where purely mathematical treatments cannot tread (for example in the weak selection-strong mutation limit), but that mathematics is crucial to validate the computational simulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Fuzzy Constraint-Based Agent Negotiation

Institute of Scientific and Technical Information of China (English)

Menq-Wen Lin; K. Robert Lai; Ting-Jung Yu

2005-01-01

Conflicts between two or more parties arise for various reasons and perspectives. Thus, resolution of conflicts frequently relies on some form of negotiation. This paper presents a general problem-solving framework for modeling multi-issue multilateral negotiation using fuzzy constraints. Agent negotiation is formulated as a distributed fuzzy constraint satisfaction problem (DFCSP). Fuzzy constrains are thus used to naturally represent each agent's desires involving imprecision and human conceptualization, particularly when lexical imprecision and subjective matters are concerned. On the other hand, based on fuzzy constraint-based problem-solving, our approach enables an agent not only to systematically relax fuzzy constraints to generate a proposal, but also to employ fuzzy similarity to select the alternative that is subject to its acceptability by the opponents. This task of problem-solving is to reach an agreement that benefits all agents with a high satisfaction degree of fuzzy constraints, and move towards the deal more quickly since their search focuses only on the feasible solution space. An application to multilateral negotiation of a travel planning is provided to demonstrate the usefulness and effectiveness of our framework.

Exosomes as mediators of platinum resistance in ovarian cancer.

Science.gov (United States)

Crow, Jennifer; Atay, Safinur; Banskota, Samagya; Artale, Brittany; Schmitt, Sarah; Godwin, Andrew K

2017-02-14

Exosomes have been implicated in the cell-cell transfer of oncogenic proteins and genetic material. We speculated this may be one mechanism by which an intrinsically platinum-resistant population of epithelial ovarian cancer (EOC) cells imparts its influence on surrounding tumor cells. To explore this possibility we utilized a platinum-sensitive cell line, A2780 and exosomes derived from its resistant subclones, and an unselected, platinum-resistant EOC line, OVCAR10. A2780 cells demonstrate a ~2-fold increase in viability upon treatment with carboplatin when pre-exposed to exosomes from platinum-resistant cells as compared to controls. This coincided with increased epithelial to mesenchymal transition (EMT). DNA sequencing of EOC cell lines revealed previously unreported somatic mutations in the Mothers Against Decapentaplegic Homolog 4 (SMAD4) within platinum-resistant cells. A2780 cells engineered to exogenously express these SMAD4 mutations demonstrate up-regulation of EMT markers following carboplatin treatment, are more resistant to carboplatin, and release exosomes which impart a ~1.7-fold increase in resistance in naive A2780 recipient cells as compared to controls. These studies provide the first evidence that acquired SMAD4 mutations enhance the chemo-resistance profile of EOC and present a novel mechanism in which exchange of tumor-derived exosomes perpetuates an EMT phenotype, leading to the development of subpopulations of platinum-refractory cells.

Agent-based land markets: Heterogeneous agents, land proces and urban land use change

NARCIS (Netherlands)

Filatova, Tatiana; Parker, Dawn C.; van der Veen, A.; Amblard, F.

2007-01-01

We construct a spatially explicit agent-based model of a bilateral land market. Heterogeneous agents form their bid and ask prices for land based on the utility that they obtain from a certain location (houte/land) and base on the state of the market (an excess of demand or supply). We underline the

One-step electrochemically-codeposited polyaniline-platinum for dye-sensitized solar cell applications

Energy Technology Data Exchange (ETDEWEB)

Thiangkaew, Anongnad; Keothongkham, Khamsone; Maiaugree, Wasan; Jarernboon, Wirat [Khon Kaen University, Khon Kaen (Thailand); Kamwanna, Teerasak; Pimanpang, Samuk; Amornkitbamrung, Vittaya [Khon Kaen University, Khon Kaen (Thailand); Nanotec-KKU Center of Excellence on Advanced Nanomaterials for Energy Production and Storage, Khon Kaen (Thailand)

2014-05-15

Platinum, polyaniline and composite polyaniline-platinum films were coated on conductive glass by using electrochemical deposition. They were then used as dye-sensitized solar cell counter electrodes. The efficiencies of platinum, polyaniline and composite polyaniline-platinum cells were 2.47, 4.47 and 6.62%, respectively. The improvement of composite polyaniline-platinum solar cell efficiency over pure polyaniline and platinum cells is because of an increase in the film's catalytic activity and a decrease in charge-transfer resistance between its counter electrode and electrolyte, as observed by using cyclic voltammogram and electrochemical impedance spectroscopy measurements, respectively. Co-deposition of polyaniline and Pt catalysts was confirmed by the presence of Pt and N peaks in the X-ray photoelectron spectroscopy spectrum.

Platinum Concentration and Pathologic Response to Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer.

Directory of Open Access Journals (Sweden)

Elizabeth A Guancial

Full Text Available Platinum (Pt-based chemotherapy is the standard of care for muscle-invasive bladder cancer (MIBC. However, resistance is a major limitation. Reduced intratumoral drug accumulation is an important mechanism of platinum resistance. Our group previously demonstrated a significant correlation between tissue Pt concentration and tumor response to Pt-based neoadjuvant chemotherapy (NAC in lung cancer. We hypothesized that increased Pt concentration in radical cystectomy (RC specimens would correlate with improved pathologic response to Pt-based NAC in MIBC.A cohort of 19 clinically annotated, archived, fresh frozen RC specimens from patients with MIBC treated with Pt-based NAC was identified [ypT0 (pathologic complete response, pCR, N = 4; ≤ypT1N0M0 (pathologic partial response, pPR, N = 6; ≥ypT2 (minimal pathologic response/progression, N = 9]. RC specimens from 2 patients with MIBC who did not receive NAC and 1 treated with a non-Pt containing NAC regimen were used as negative controls. Total Pt concentration in normal adjacent urothelial tissue and bladder tumors from RC specimens was measured by flameless atomic absorption spectrophotometry.Total Pt concentration in normal urothelium differed by tumor pathologic response (P = 0.011. Specimens with pCR had the highest Pt concentrations compared to those with pPR (P = 0.0095 or no response/progression (P = 0.020. There was no significant difference in Pt levels in normal urothelium and tumor between pPR and no response/progression groups (P = 0.37; P = 0.25, respectively.Our finding of increased intracellular Pt in RC specimens with pCR following NAC for MIBC compared to those with residual disease suggests that enhanced Pt accumulation may be an important determinant of Pt sensitivity. Factors that modulate intracellular Pt concentration, such as expression of Pt transporters, warrant further investigation as predictive biomarkers of response to Pt-based NAC in MIBC.

Phase-field model for deposition process of platinum nanoparticles on carbon substrate

International Nuclear Information System (INIS)

Yamakawa, S; Hyodo, S; Okazaki-Maeda, K; Kohyama, M

2008-01-01

Platinum supported on a carbon carrier is widely used as a catalyst for polymer electrolyte membrane fuel cells. The catalytic activity is significantly affected by the size distribution and morphologies of the platinum particles. The objective of this study is to extend the phase-field approach to describe the formation process of platinum particles onto the substrate. The microstructural evolution of a nanoparticle was represented by the temporal evolution of the field variables related to the platinum concentration, long-range crystallographic ordering and phase transition. First-principles calculations were performed in order to estimate the interaction energies between several different types of platinum clusters and a graphene sheet. The platinum density profile concentrated over the substrate surface led to the formation of three-dimensional islands in accordance with the Volmer-Weber mode of growth. The size distributions of the platinum particles were sensitive to the heterogeneity of the substrate surface and to the competitive nucleation and growth processes

Recent advances in agent-based complex automated negotiation

CERN Document Server

Ito, Takayuki; Zhang, Minjie; Fujita, Katsuhide; Robu, Valentin

2016-01-01

This book covers recent advances in Complex Automated Negotiations as a widely studied emerging area in the field of Autonomous Agents and Multi-Agent Systems. The book includes selected revised and extended papers from the 7th International Workshop on Agent-Based Complex Automated Negotiation (ACAN2014), which was held in Paris, France, in May 2014. The book also includes brief introductions about Agent-based Complex Automated Negotiation which are based on tutorials provided in the workshop, and brief summaries and descriptions about the ANAC'14 (Automated Negotiating Agents Competition) competition, where authors of selected finalist agents explain the strategies and the ideas used by them. The book is targeted to academic and industrial researchers in various communities of autonomous agents and multi-agent systems, such as agreement technology, mechanism design, electronic commerce, related areas, as well as graduate, undergraduate, and PhD students working in those areas or having interest in them.

An impending platinum crisis and its implications for the future of the automobile

International Nuclear Information System (INIS)

Yang, C.-J.

2009-01-01

The global demand for platinum has consistently outgrown supply in the past decade. This trend likely will continue and the imbalance may possibly escalate into a crisis. Platinum plays pivotal roles in both conventional automobile emissions control and the envisioned hydrogen economy. A platinum crisis would have profound implications on energy and environment. On the one hand, inadequate platinum supply will prevent widespread commercialization of hydrogen fuel-cell vehicles. On the other hand, expensive platinum may enhance the competitiveness of hybrid, plug-in hybrid, and battery-powered electric cars. Policymakers should weigh the potential impacts of a platinum crisis in energy policy.

Agent Based Reasoning in Multilevel Flow Modeling

DEFF Research Database (Denmark)

Lind, Morten; Zhang, Xinxin

2012-01-01

to launch the MFM Workbench into an agent based environment, which can complement disadvantages of the original software. The agent-based MFM Workbench is centered on a concept called “Blackboard System” and use an event based mechanism to arrange the reasoning tasks. This design will support the new...

Polymorphisms in XPD gene could predict clinical outcome of platinum-based chemotherapy for non-small cell lung cancer patients: a meta-analysis of 24 studies.

Directory of Open Access Journals (Sweden)

Qin Qin

Full Text Available OBJECTIVE: Xeroderma pigmentosum group D (XPD is an essential gene involved in the nucleotide excision repair (NER pathway. Two commonly studied single nucleotide polymorphisms (SNPs of XPD (Lys751Gln, A>C, rs13181; Asp312Asn, G>A, rs1799793 are implicated in the modulation of DNA repair capacity, thus related to the responses to platinum-based chemotherapy. Here we performed a meta-analysis to better evaluate the association between the two XPD SNPs and clinical outcome of platinum-based chemotherapy in non-small cell lung cancer (NSCLC patients. METHODS: A comprehensive search of PubMed database was conducted to identify relevant articles. Primary outcomes included objective response (i.e., complete response + partial response vs. stable disease + progressive disease, progression-free survival (PFS and overall survival (OS. The pooled and 95% confidence intervals (CIs of ORs (odds ratios and HRs (hazard ratios were estimated using the fixed or random effect model. RESULTS: Twenty-four studies were eligible according to the inclusion criteria. None of the XPD Lys751Gln/Asp312Asn polymorphisms was associated with objective response, PFS or OS in NSCLC patients treated with platinum drugs. However, in stratified analysis by ethnicity, the XPD Lys751Gln (A>C polymorphism was not significantly associated with increased response in Caucasians (OR=1.35, 95%CI=1.0-1.83, P=0.122 for heterogeneity but was associated with decreased PFS in Asians (HR=1.39, 95%CI=1.07-1.81, P=0.879 for heterogeneity. Furthermore, a statistically significant difference existed in the estimates of effect between the two ethnicities (P=0.014 for TR; PC may have inverse predictive and prognostic role in platinum-based treatment of NSCLC according to different ethnicities. Further studies are needed to validate our findings.

Agent Based Modeling Applications for Geosciences

Science.gov (United States)

Stein, J. S.

2004-12-01

Agent-based modeling techniques have successfully been applied to systems in which complex behaviors or outcomes arise from varied interactions between individuals in the system. Each individual interacts with its environment, as well as with other individuals, by following a set of relatively simple rules. Traditionally this "bottom-up" modeling approach has been applied to problems in the fields of economics and sociology, but more recently has been introduced to various disciplines in the geosciences. This technique can help explain the origin of complex processes from a relatively simple set of rules, incorporate large and detailed datasets when they exist, and simulate the effects of extreme events on system-wide behavior. Some of the challenges associated with this modeling method include: significant computational requirements in order to keep track of thousands to millions of agents, methods and strategies of model validation are lacking, as is a formal methodology for evaluating model uncertainty. Challenges specific to the geosciences, include how to define agents that control water, contaminant fluxes, climate forcing and other physical processes and how to link these "geo-agents" into larger agent-based simulations that include social systems such as demographics economics and regulations. Effective management of limited natural resources (such as water, hydrocarbons, or land) requires an understanding of what factors influence the demand for these resources on a regional and temporal scale. Agent-based models can be used to simulate this demand across a variety of sectors under a range of conditions and determine effective and robust management policies and monitoring strategies. The recent focus on the role of biological processes in the geosciences is another example of an area that could benefit from agent-based applications. A typical approach to modeling the effect of biological processes in geologic media has been to represent these processes in

Photophysics of organometallic platinum(II) derivatives of the diketopyrrolopyrrole chromophore

KAUST Repository

Goswami, Subhadip; Winkel, Russell W.; Alarousu, Erkki; Ghiviriga, Ion; Mohammed, Omar F.; Schanze, Kirk S.

2014-01-01

A pair of diketopyrrolopyrrole (DPP) chromophores that are end-functionalized with platinum containing "auxochromes" were subjected to electrochemical and photophysical study. The chromophores contain either platinum acetylide or ortho-metalated 2-thienylpyridinyl(platinum) end-groups (DPP-Pt(CC) and DPP-Pt(acac), respectively). The ground state redox potentials of the chromophores were determined by solution electrochemistry, and the HOMO and LUMO levels were estimated. The chromophores' photophysical properties were characterized by absorption, photoluminescence, and time-resolved absorption spectroscopy on time scales from sub-picoseconds to microseconds. Density functional theory (DFT) computations were performed to understand the molecular orbitals involved in both the singlet and triplet excited state photophysics. The results reveal that in both platinum DPP derivatives the organometallic auxochromes have a significant effect on the chromophores' photophysics. The most profound effect is a reduction in the fluorescence yields accompanied by enhanced triplet yields due to spin-orbit coupling induced by the metal centers. The effects are most pronounced in DPP-Pt(acac), indicating that the orthometalated platinum auxochrome is able to induce spin-orbital coupling to a greater extent compared to the platinum acetylide units. (Figure Presented).

In vitro permeation of platinum and rhodium through Caucasian skin.

Science.gov (United States)

Franken, A; Eloff, F C; Du Plessis, J; Badenhorst, C J; Jordaan, A; Du Plessis, J L

2014-12-01

During platinum group metals (PGMs) refining the possibility exists for dermal exposure to PGM salts. The dermal route has been questioned as an alternative route of exposure that could contribute to employee sensitisation, even though literature has been focused on respiratory exposure. This study aimed to investigate the in vitro permeation of platinum and rhodium through intact Caucasian skin. A donor solution of 0.3mg/ml of metal, K2PtCl4 and RhCl3 respectively, was applied to the vertical Franz diffusion cells with full thickness abdominal skin. The receptor solution was removed at various intervals during the 24h experiment, and analysed with high resolution ICP-MS. Skin was digested and analysed by ICP-OES. Results indicated cumulative permeation with prolonged exposure, with a significantly higher mass of platinum permeating after 24h when compared to rhodium. The mass of platinum retained inside the skin and the flux of platinum across the skin was significantly higher than that of rhodium. Permeated and skin retained platinum and rhodium may therefore contribute to sensitisation and indicates a health risk associated with dermal exposure in the workplace. Copyright © 2014 Elsevier Ltd. All rights reserved.

Photophysics of organometallic platinum(II) derivatives of the diketopyrrolopyrrole chromophore

KAUST Repository

Goswami, Subhadip

2014-12-18

A pair of diketopyrrolopyrrole (DPP) chromophores that are end-functionalized with platinum containing "auxochromes" were subjected to electrochemical and photophysical study. The chromophores contain either platinum acetylide or ortho-metalated 2-thienylpyridinyl(platinum) end-groups (DPP-Pt(CC) and DPP-Pt(acac), respectively). The ground state redox potentials of the chromophores were determined by solution electrochemistry, and the HOMO and LUMO levels were estimated. The chromophores\\' photophysical properties were characterized by absorption, photoluminescence, and time-resolved absorption spectroscopy on time scales from sub-picoseconds to microseconds. Density functional theory (DFT) computations were performed to understand the molecular orbitals involved in both the singlet and triplet excited state photophysics. The results reveal that in both platinum DPP derivatives the organometallic auxochromes have a significant effect on the chromophores\\' photophysics. The most profound effect is a reduction in the fluorescence yields accompanied by enhanced triplet yields due to spin-orbit coupling induced by the metal centers. The effects are most pronounced in DPP-Pt(acac), indicating that the orthometalated platinum auxochrome is able to induce spin-orbital coupling to a greater extent compared to the platinum acetylide units. (Figure Presented).

Systemic use of tumor necrosis factor alpha as an anticancer agent

Science.gov (United States)

Roberts, Nicholas J.; Zhou, Shibin; Diaz, Luis A.; Holdhoff, Matthias

2011-01-01

Tumor necrosis factor-α (TNF-α) has been discussed as a potential anticancer agent for many years, however initial enthusiasm about its clinical use as a systemic agent was curbed due to significant toxicities and lack of efficacy. Combination of TNF-α with chemotherapy in the setting of hyperthermic isolated limb perfusion (ILP), has provided new insights into a potential therapeutic role of this agent. The therapeutic benefit from TNF-α in ILP is thought to be not only due to its direct anti-proliferative effect, but also due to its ability to increase penetration of the chemotherapeutic agents into the tumor tissue. New concepts for the use of TNF-α as a facilitator rather than as a direct actor are currently being explored with the goal to exploit the ability of this agent to increase drug delivery and to simultaneously reduce systemic toxicity. This review article provides a comprehensive overview on the published previous experience with systemic TNF-α. Data from 18 phase I and 10 phase II single agent as well as 18 combination therapy studies illustrate previously used treatment and dose schedules, response data as well as the most prominently observed adverse effects. Also discussed, based on recent preclinical data, is a potential future role of systemic TNF-α in combination with liposomal chemotherapy to facilitate increased drug uptake into tumors. PMID:22036896

Multi-issue Agent Negotiation Based on Fairness

Science.gov (United States)

Zuo, Baohe; Zheng, Sue; Wu, Hong

Agent-based e-commerce service has become a hotspot now. How to make the agent negotiation process quickly and high-efficiently is the main research direction of this area. In the multi-issue model, MAUT(Multi-attribute Utility Theory) or its derived theory usually consider little about the fairness of both negotiators. This work presents a general model of agent negotiation which considered the satisfaction of both negotiators via autonomous learning. The model can evaluate offers from the opponent agent based on the satisfaction degree, learn online to get the opponent's knowledge from interactive instances of history and negotiation of this time, make concessions dynamically based on fair object. Through building the optimal negotiation model, the bilateral negotiation achieved a higher efficiency and fairer deal.

Permeation of platinum and rhodium nanoparticles through intact and damaged human skin

International Nuclear Information System (INIS)

Mauro, Marcella; Crosera, Matteo; Bianco, Carlotta; Adami, Gianpiero; Montini, Tiziano; Fornasiero, Paolo; Jaganjac, Morana; Bovenzi, Massimo; Filon, Francesca Larese

2015-01-01

The aim of the study was to evaluate percutaneous penetration of platinum and rhodium nanoparticles (PtNPs: 5.8 ± 0.9 nm, RhNPs: 5.3 ± 1.9 nm) through human skin. Salts compounds of these metals are sensitizers and some also carcinogenic agents. In vitro permeation experiments were performed using Franz diffusion cells with intact and damaged skin. PtNPs and RhNPs, stabilized with polyvinylpyrrolidone, were synthesized by reduction of Na 2 PtC l6 and RhCl 3 ·3H 2 O respectively. Suspensions with a concentration of 2.0 g/L of PtNPs and RhNPs were dispersed separately in synthetic sweat at pH 4.5 and applied as donor phases to the outer surface of the skin for 24 h. Measurements of the content of the metals in the receiving solution and in the skin were performed subsequently. Rhodium skin permeation was demonstrated through damaged skin, with a permeation flux of 0.04 ± 0.04 μg cm −2  h −1 and a lag time of 7.9 ± 1.1 h, while no traces of platinum were found in receiving solutions. Platinum and rhodium skin-analysis showed significantly higher concentrations of the metals in damaged skin. Rh and Pt applied as NPs can penetrate the skin barrier and Rh can be found in receiving solutions. These experiments pointed out the need for skin contamination prevention, since even a minor injury to the skin barrier can significantly increase penetration

Permeation of platinum and rhodium nanoparticles through intact and damaged human skin

Energy Technology Data Exchange (ETDEWEB)

Mauro, Marcella [University of Trieste, Clinical Unit of Occupational Medicine, Department of Medical Sciences (Italy); Crosera, Matteo; Bianco, Carlotta; Adami, Gianpiero; Montini, Tiziano; Fornasiero, Paolo [University of Trieste, Department of Chemical and Pharmaceutical Sciences (Italy); Jaganjac, Morana [Rudjer Boskovic Institute, Laboratory for Oxidative Stress, Department of Molecular Medicine (Croatia); Bovenzi, Massimo; Filon, Francesca Larese, E-mail: larese@units.it [University of Trieste, Clinical Unit of Occupational Medicine, Department of Medical Sciences (Italy)

2015-06-15

The aim of the study was to evaluate percutaneous penetration of platinum and rhodium nanoparticles (PtNPs: 5.8 ± 0.9 nm, RhNPs: 5.3 ± 1.9 nm) through human skin. Salts compounds of these metals are sensitizers and some also carcinogenic agents. In vitro permeation experiments were performed using Franz diffusion cells with intact and damaged skin. PtNPs and RhNPs, stabilized with polyvinylpyrrolidone, were synthesized by reduction of Na{sub 2}PtC{sub l6} and RhCl{sub 3}·3H{sub 2}O respectively. Suspensions with a concentration of 2.0 g/L of PtNPs and RhNPs were dispersed separately in synthetic sweat at pH 4.5 and applied as donor phases to the outer surface of the skin for 24 h. Measurements of the content of the metals in the receiving solution and in the skin were performed subsequently. Rhodium skin permeation was demonstrated through damaged skin, with a permeation flux of 0.04 ± 0.04 μg cm{sup −2} h{sup −1} and a lag time of 7.9 ± 1.1 h, while no traces of platinum were found in receiving solutions. Platinum and rhodium skin-analysis showed significantly higher concentrations of the metals in damaged skin. Rh and Pt applied as NPs can penetrate the skin barrier and Rh can be found in receiving solutions. These experiments pointed out the need for skin contamination prevention, since even a minor injury to the skin barrier can significantly increase penetration.

Gallium a unique anti-resorptive agent in bone: Preclinical studies on its mechanisms of action

International Nuclear Information System (INIS)

Bockman, R.; Adelman, R.; Donnelly, R.; Brody, L.; Warrell, R.; Jones, K.W.

1990-01-01

The discovery of gallium as a new and unique agent for the treatment of metabolic bone disorders was in part fortuitous. Gallium is an exciting new therapeutic agent for the treatment of pathologic states characterized by accelerated bone resorption. Compared to other therapeutic metal compounds containing platinum or germanium, gallium affects its antiresorptive action without any evidence of a cytotoxic effect on bone cells. Gallium is unique amongst all therapeutically available antiresorptive agents in that it favors bone formation. 18 refs., 1 fig

Experimental FT-IR, Laser-Raman and DFT spectroscopic analysis of a potential chemotherapeutic agent 6-(2-methylpropyl)-4-oxo-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile.

Science.gov (United States)

Sert, Yusuf; Al-Turkistani, Abdulghafoor A; Al-Deeb, Omar A; El-Emam, Ali A; Ucun, Fatih; Çırak, Çağrı

2014-01-01

In this study, the experimental and theoretical vibrational frequencies of a newly synthesized potential chemotherapeutic agent namely, 6-(2-methylpropyl)-4-oxo-2-sulfanylidene-1,2,3,4-tetrahydropyrimidine-5-carbonitrile have been investigated. The experimental FT-IR (4000-400 cm(-1)) and Laser-Raman spectra (4000-100 cm(-1)) of the molecule in solid phase have been recorded. The theoretical vibrational frequencies and optimized geometric parameters (bond lengths and bond angles) have been calculated by using density functional theory (DFT/B3LYP: Becke, 3-parameter, Lee-Yang-Parr) and M06-2X (the highly parametrized, empirical exchange correlation function) quantum chemical methods with 6-311++G(d,p) basis set by Gaussian 09 W software, for the first time. The assignments of the vibrational frequencies have been done by potential energy distribution (PED) analysis by using VEDA 4 software. The theoretical optimized geometric parameters and vibrational frequencies have been found to be in good agreement with the corresponding experimental data, and with the results in the literature. In addition, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energies and the other related molecular energy values have been calculated and depicted. Copyright © 2013 Elsevier B.V. All rights reserved.

CYB5D2 requires heme-binding to regulate HeLa cell growth and confer survival from chemotherapeutic agents.

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Anthony Bruce

Full Text Available The cytochrome b5 domain containing 2 (CYB5D2; Neuferricin protein has been reported to bind heme, however, the critical residues responsible for heme-binding are undefined. Furthermore, the relationship between heme-binding and CYB5D2-mediated intracellular functions remains unknown. Previous studies examining heme-binding in two cytochrome b5 heme-binding domain-containing proteins, damage-associated protein 1 (Dap1; Saccharomyces cerevisiae and human progesterone receptor membrane component 1 (PGRMC1, have revealed that conserved tyrosine (Y 73, Y79, aspartic acid (D 86, and Y127 residues present in human CYB5D2 may be involved in heme-binding. CYB5D2 binds to type b heme, however, only the substitution of glycine (G at D86 (D86G within its cytochrome b5 heme-binding (cyt-b5 domain abolished its heme-binding ability. Both CYB5D2 and CYB5D2(D86G localize to the endoplasmic reticulum. Ectopic CYB5D2 expression inhibited cell proliferation and anchorage-independent colony growth of HeLa cells. Conversely, CYB5D2 knockdown and ectopic CYB5D2(D86G expression increased cell proliferation and colony growth. As PGRMC1 has been reported to regulate the expression and activities of cytochrome P450 proteins (CYPs, we examined the role of CYB5D2 in regulating the activities of CYPs involved in sterol synthesis (CYP51A1 and drug metabolism (CYP3A4. CYB5D2 co-localizes with cytochrome P450 reductase (CYPOR, while CYB5D2 knockdown reduced lanosterol demethylase (CYP51A1 levels and rendered HeLa cells sensitive to mevalonate. Additionally, knockdown of CYB5D2 reduced CYP3A4 activity. Lastly, CYB5D2 expression conferred HeLa cell survival from chemotherapeutic agents (paclitaxel, cisplatin and doxorubicin, with its ability to promote survival being dependent on its heme-binding ability. Taken together, this study provides evidence that heme-binding is critical for CYB5D2 in regulating HeLa cell growth and survival, with endogenous CYB5D2 being required to

Modeling of Platinum-Aryl Interaction with Amyloid-β Peptide.

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Turner, Matthew; Platts, James A; Deeth, Robert J

2016-03-08

Ligand field molecular mechanics (LFMM), density functional theory (DFT), and semiempirical PM7 methods are used to study the binding of two Pt(II)-L systems to an N-terminal fragment of the amyloid-β peptide, where L = 2,2-bipyridyl or 1,10-phenanthroline. Molecular dynamics simulations are used to explore the conformational freedom of the peptide using LFMM combined with AMBER molecular mechanics parameters. We establish a modeling protocol, allowing for identification and analysis of favorable platinum-binding modes and peptide conformations. Preferred binding modes are identified for each ligand investigated; metal coordination occurs via Nε in His residues for both ligands--His6ε-His13ε and His6ε-His14ε for the bipyridyl and phenanthroline ligands, respectively. The observed change in binding mode for the different ligands suggests that the binding mode of these platinum-based structures can be controlled by the choice of ligand. In the bipy systems, Boltzmann population at 310 K is dominated by a single conformer, while in the phenanthroline case, three conformations make significant contributions to the ensemble. The relative stability of these conformations is due to the inherent stability of binding platinum via Nε in addition to subtle H-bonding effects.

Agent-based models in economics a toolkit

CERN Document Server

Fagiolo, Giorgio; Gallegati, Mauro; Richiardi, Matteo; Russo, Alberto

2018-01-01

In contrast to mainstream economics, complexity theory conceives the economy as a complex system of heterogeneous interacting agents characterised by limited information and bounded rationality. Agent Based Models (ABMs) are the analytical and computational tools developed by the proponents of this emerging methodology. Aimed at students and scholars of contemporary economics, this book includes a comprehensive toolkit for agent-based computational economics, now quickly becoming the new way to study evolving economic systems. Leading scholars in the field explain how ABMs can be applied fruitfully to many real-world economic examples and represent a great advancement over mainstream approaches. The essays discuss the methodological bases of agent-based approaches and demonstrate step-by-step how to build, simulate and analyse ABMs and how to validate their outputs empirically using the data. They also present a wide set of applications of these models to key economic topics, including the business cycle, lab...

Electrochemical behavior of platinum nanoparticles on a carbon xerogel support modified with a [(trifluoromethyl)-benzenesulfonyl]imide electrolyte.

Science.gov (United States)

Liu, Bing; Mei, Hua; DesMarteau, Darryl; Creager, Stephen E

2014-12-11

A monoprotic [(trifluoromethyl)benzenesulfonyl]imide (SI) superacid electrolyte was used to covalently modify a mesoporous carbon xerogel (CX) support via reaction of the corresponding trifluoromethyl aryl sulfonimide diazonium zwitterion with the carbon surface. Electrolyte attachment was demonstrated by elemental analysis, acid-base titration, and thermogravimetric analysis. The ion-exchange capacity of the fluoroalkyl-aryl-sulfonimide-grafted carbon xerogel (SI-CX) was ∼0.18 mequiv g(-1), as indicated by acid-base titration. Platinum nanoparticles were deposited onto the SI-grafted carbon xerogel samples by the impregnation and reduction method, and these materials were employed to fabricate polyelectrolyte membrane fuel-cell (PEMFC) electrodes by the decal transfer method. The SI-grafted carbon-xerogel-supported platinum (Pt/SI-CX) was characterized by X-ray diffraction and transmission electron microscopy to determine platinum nanoparticle size and distribution, and the findings are compared with CX-supported platinum catalyst without the grafted SI electrolyte (Pt/CX). Platinum nanoparticle sizes are consistently larger on Pt/SI-CX than on Pt/CX. The electrochemically active surface area (ESA) of platinum catalyst on the Pt/SI-CX and Pt/CX samples was measured with ex situ cyclic voltammetry (CV) using both hydrogen adsorption/desorption and carbon monoxide stripping methods and by in situ CV within membrane electrode assemblies (MEAs). The ESA values for Pt/SI-CX are consistently lower than those for Pt/CX. Some possible reasons for the behavior of samples with and without grafted SI layers and implications for the possible use of SI-grafted carbon layers in PEMFC devices are discussed.

1 ALPHA-Hydroxyvitamin D5 as a Chemotherapeutic and Possibly Chemopreventive Agent

Science.gov (United States)

2004-09-01

cancer cells. TTT TG. The primer -for the housekeeping gene G3PDH was purchased from ClonTech. The touchdown 3.2. Induction of differentiation of breast...the housekeeping gene The effects of vitamin D analogues as differentiating G3PDH (C) was identical for all the cDNAs, indicating . agents and...control housekeeping gene. "* G. Lazzaro et al. / European Journal of Cancer 36 (2000) 780-786 785 levels of VDR, do not respond to active vitamin D p53

The RSC Faraday prize lecture of 1989 on platinum.

Science.gov (United States)

Thomas, John Meurig

2017-08-25

In 1861, Michael Faraday gave one of his last Friday Evening Discourses at the Royal Institution of Great Britain, London, on platinum, which he described as "this beautiful, magnificent and valuable metal". More than a hundred and twenty years later (in 1989), the author re-enacted, at the Royal Institution, many of the demonstrations that Faraday carried out in his memorable Discourse. This article outlines many of Faraday's views on, and experiments with, platinum. It also describes the continuing importance and utilization of platinum, both as perceived in 1989 and from present perspectives.

Bioactive albumin-based carriers for tumour chemotherapy.

Science.gov (United States)

Shahzad, Yasser; Khan, Ikram Ullah; Hussain, Talib; Alamgeer; Serra, Christophe A; Rizvi, Syed A A; Gerber, Minja; du Plessis, Jeanetta

2014-01-01

Proteins are posed as the natural counterpart of the synthetic polymers for the development of drug delivery systems and few of them, have been regarded safe for drug delivery purposes by the United States Food and Drug Administration (FDA). Serum albumin is the most abundant protein in human blood. Interest in the exploration of pharmaceutical applications of albumin-based drug delivery carriers, especially for the delivery of chemotherapeutic agents, has increased in recent years. Albumin has several advantages over synthetic polymers, as it is biocompatible, biodegradable, has low cytotoxicity and has an excellent binding capacity with various drugs. Micro- and nano-carriers not only protect active pharmaceutical ingredients against degradation, but also offer a prolonged release of drugs in a controlled fashion. Since existing tumour chemotherapeutic agents neither target tumour cells, nor are they specific to tumour cells, a slow release of drugs from carriers would be beneficial in targeting carcinogenic cells intracellularly. This article aims at providing an overview of pharmaceutical applications of albumin as a drug delivery carrier in tumour chemotherapy.

An aCGH classifier derived from BRCA1-mutated breast cancer and benefit of high-dose platinum-based chemotherapy in HER2-negative breast cancer patients

NARCIS (Netherlands)

Vollebergh, M. A.; Lips, E. H.; Nederlof, P. M.; Wessels, L. F. A.; Schmidt, M. K.; van Beers, E. H.; Cornelissen, S.; Holtkamp, M.; Froklage, F. E.; de Vries, E. G. E.; Schrama, J. G.; Wesseling, J.; van de Vijver, M. J.; van Tinteren, H.; de Bruin, M.; Hauptmann, M.; Rodenhuis, S.; Linn, S. C.

Patients and methods: We evaluated this classifier in stage III breast cancer patients, who had been randomly assigned between adjuvant high-dose platinum-based (HD-PB) chemotherapy, a DSB-inducing regimen, and conventional anthracycline-based chemotherapy. Additionally, we assessed BRCA1 loss

Single-Atom Catalyst of Platinum Supported on Titanium Nitride for Selective Electrochemical Reactions.

Science.gov (United States)

Yang, Sungeun; Kim, Jiwhan; Tak, Young Joo; Soon, Aloysius; Lee, Hyunjoo

2016-02-05

As a catalyst, single-atom platinum may provide an ideal structure for platinum minimization. Herein, a single-atom catalyst of platinum supported on titanium nitride nanoparticles were successfully prepared with the aid of chlorine ligands. Unlike platinum nanoparticles, the single-atom active sites predominantly produced hydrogen peroxide in the electrochemical oxygen reduction with the highest mass activity reported so far. The electrocatalytic oxidation of small organic molecules, such as formic acid and methanol, also exhibited unique selectivity on the single-atom platinum catalyst. A lack of platinum ensemble sites changed the reaction pathway for the oxygen-reduction reaction toward a two-electron pathway and formic acid oxidation toward direct dehydrogenation, and also induced no activity for the methanol oxidation. This work demonstrates that single-atom platinum can be an efficient electrocatalyst with high mass activity and unique selectivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Coatings of Different Carbon Nanotubes on Platinum Electrodes for Neuronal Devices: Preparation, Cytocompatibility and Interaction with Spiral Ganglion Cells.

Science.gov (United States)

Burblies, Niklas; Schulze, Jennifer; Schwarz, Hans-Christoph; Kranz, Katharina; Motz, Damian; Vogt, Carla; Lenarz, Thomas; Warnecke, Athanasia; Behrens, Peter

2016-01-01

Cochlear and deep brain implants are prominent examples for neuronal prostheses with clinical relevance. Current research focuses on the improvement of the long-term functionality and the size reduction of neural interface electrodes. A promising approach is the application of carbon nanotubes (CNTs), either as pure electrodes but especially as coating material for electrodes. The interaction of CNTs with neuronal cells has shown promising results in various studies, but these appear to depend on the specific type of neurons as well as on the kind of nanotubes. To evaluate a potential application of carbon nanotube coatings for cochlear electrodes, it is necessary to investigate the cytocompatibility of carbon nanotube coatings on platinum for the specific type of neuron in the inner ear, namely spiral ganglion neurons. In this study we have combined the chemical processing of as-delivered CNTs, the fabrication of coatings on platinum, and the characterization of the electrical properties of the coatings as well as a general cytocompatibility testing and the first cell culture investigations of CNTs with spiral ganglion neurons. By applying a modification process to three different as-received CNTs via a reflux treatment with nitric acid, long-term stable aqueous CNT dispersions free of dispersing agents were obtained. These were used to coat platinum substrates by an automated spray-coating process. These coatings enhance the electrical properties of platinum electrodes, decreasing the impedance values and raising the capacitances. Cell culture investigations of the different CNT coatings on platinum with NIH3T3 fibroblasts attest an overall good cytocompatibility of these coatings. For spiral ganglion neurons, this can also be observed but a desired positive effect of the CNTs on the neurons is absent. Furthermore, we found that the well-established DAPI staining assay does not function on the coatings prepared from single-wall nanotubes.

Bimetallic alloy electrocatalysts with multilayered platinum-skin surfaces

Science.gov (United States)

Stamenkovic, Vojislav R.; Wang, Chao; Markovic, Nenad M.

2016-01-26

Compositions and methods of preparing a bimetallic alloy having enhanced electrocatalytic properties are provided. The composition comprises a PtNi substrate having a surface layer, a near-surface layer, and an inner layer, where the surface layer comprises a nickel-depleted composition, such that the surface layer comprises a platinum skin having at least one atomic layer of platinum.

Contrast agent based on nano-emulsion for targeted biomedical imaging

International Nuclear Information System (INIS)

Attia, Mohamed

2016-01-01

poly(maleic anhydride-alt-1-octadecene) (PMAO). The in vitro results and in vivo evaluations were completely coherent approving that the neutral charged NPs are less toxic compared to the negatively charged ones that were highly up-taken in the cells causing stress to the cells and thereby affecting the toxicity. As a result they are different in biodistribution and pharmacokinetics. In this context, for the first time, we were able to functionalize the nano-emulsion droplets with ligand molecules by covalent bonds. Likewise we designed nano-droplets and coated by silica shell ended by amino groups and then followed by formation of amide bonds with grafting to dye ligand model (coumarin blue dye). The quantification of amino groups was performed by using spectroscopic and microscopic techniques, with a grafting efficiency as high as 41%. This process improves the targeting properties of such chemotherapeutic agents to the location of interest following active targeting mechanism (ligand receptor strategy). One of our achieved objectives was to engineer multifunctional polymer-based NPs encapsulating hydrophobic drug model as DDs and iron oxide NPs as a theranostic model. To conclude, novel contrast agents and delivering systems were synthesized with outstanding physicochemical characteristics and suitable for in vivo medium with high efficacy and low toxicity [fr

Tunable morphological properties of silver enriched platinum allied nanoparticles and their catalysed reduction of p-nitrophenol

International Nuclear Information System (INIS)

Adekoya, Joseph Adeyemi; Dare, Enock Olugbenga; Mesubi, Michael Adediran

2014-01-01

A robust polymer based and polyol mediated procedure to synthesize nanobimetallic particles has been modified to produce core–shell and alloy Ag/Pt nanoparticles with tunable properties. Novel three-dimensional (3D) quasi nanocubes entangled in nanowebs were produced by rapid solution phase transformation with hot addition of absolute ethanol. The optical characterization showed extinction of plasmon resonance band occurring with incremental feeding ratio of Pt source in all cases. Transmission electron microscope (TEM) and high resolution transmission electron microscope (HRTEM) images revealed that the shape, size and size distribution of as-prepared silver platinum nanoparticles depended on the stabilizer or capping agent, mole ratio of metal ion sources, temperature and time of reaction. Meanwhile, catalytic activity was highest in the reduction of p-nitrophenol in the presence of polyvinylpyrrolidone/diethylene glycol stabilized Ag/Pt nanoparticles. (paper)

Tunable morphological properties of silver enriched platinum allied nanoparticles and their catalysed reduction of p-nitrophenol

Science.gov (United States)

Adeyemi Adekoya, Joseph; Olugbenga Dare, Enock; Adediran Mesubi, Michael

2014-09-01

A robust polymer based and polyol mediated procedure to synthesize nanobimetallic particles has been modified to produce core-shell and alloy Ag/Pt nanoparticles with tunable properties. Novel three-dimensional (3D) quasi nanocubes entangled in nanowebs were produced by rapid solution phase transformation with hot addition of absolute ethanol. The optical characterization showed extinction of plasmon resonance band occurring with incremental feeding ratio of Pt source in all cases. Transmission electron microscope (TEM) and high resolution transmission electron microscope (HRTEM) images revealed that the shape, size and size distribution of as-prepared silver platinum nanoparticles depended on the stabilizer or capping agent, mole ratio of metal ion sources, temperature and time of reaction. Meanwhile, catalytic activity was highest in the reduction of p-nitrophenol in the presence of polyvinylpyrrolidone/diethylene glycol stabilized Ag/Pt nanoparticles.

Characterization and bacterial anti-adherent effect on modified PMMA denture acrylic resin containing platinum nanoparticles

OpenAIRE

Nam, Ki-Young

2014-01-01

PURPOSE This study characterized the synthesis of a modified PMMA (Polymethyl methacrylate) denture acrylic loading platinum nanoparticles (PtN) and assessed its bacterial inhibitory efficacy to produce novel antimicrobial denture base material. MATERIALS AND METHODS Polymerized PMMA denture acrylic disc (20 mm × 2 mm) specimens containing 0 (control), 10, 50, 100 and 200 mg/L of PtN were fabricated respectively. The obtained platinum-PMMA nanocomposite (PtNC) was characterized by TEM (transm...

Platinum Monolayer Electrocatalysts for Anodic Oxidation of Alcohols.

Science.gov (United States)

Li, Meng; Liu, Ping; Adzic, Radoslav R

2012-12-06

The slow, incomplete oxidation of methanol and ethanol on platinum-based anodes as well as the high price and limited reserves of Pt has hampered the practical application of direct alcohol fuel cells. We describe the electrocatalysts consisting of one Pt monolayer (one atom thick layer) placed on extended or nanoparticle surfaces having the activity and selectivity for the oxidation of alcohol molecules that can be controlled with platinum-support interaction. The suitably expanded Pt monolayer (i.e., Pt/Au(111)) exhibits a factor of 7 activity increase in catalyzing methanol electrooxidation relative to Pt(111). Sizable enhancement is also observed for ethanol electrooxidation. Furthermore, a correlation between substrate-induced lateral strain in a Pt monolayer and its activity/selectivity is established and rationalized by experimental and theoretical studies. The knowledge we gained with single-crystal model catalysts was successfully applied in designing real nanocatalysts. These findings for alcohols are likely to be applicable for the oxidation of other classes of organic molecules.

Studies on the distribution of platinum in tumour-bearing rats after the administration of platinum co-ordination complexes used in cancer chemotherapy

International Nuclear Information System (INIS)

Zeisler, R.; Lux, F.; Beck, W.

1979-01-01

Platinum co-ordination complexes like dichlorodiamineplatinum(II) (DDP) feature broad spectrum antitumour activity which, however, is marred by a certain toxicity related especially to renal tubular damage. The activity of such drugs depends on the chemical structure of the complexes, with changes in the ligands resulting in changes in their antitumour activity and toxicity. Assessments of the biological and toxicological effects of recently synthesized complexes must include distribution studies of platinum in the body. It is demonstrated that instrumental neutron activation analysis can be used for these studies because of its accuracy, precision and the low detection limit for platinum (approximately equal to 2 ng), when a standardized method is used. The time-dependent retention of platinum was determined in blood, liver, kidneys and cells of ascitic Walker 256 carcinosarcoma in tumour-bearing rats and controls after the administration of the cis-Pt(Gly-Gly-0Et) 2 Cl 2 complex. Two series of experiments, one with the therapeutic amount of the drug (80 mg/kg body weight) and one low-dose experiment with 1/100 of this amount, were carried out. The results of both experiments are discussed with regard to changes in the platinum concentration with time (0-48 h) in the different samples. From the data a selective uptake of the drug by the tumour cells, causing their destruction, is deduced. Because this drug has shown excellent antitumour activity, this observed selectivity suggests promise for its application in cancer chemotherapy, although platinum retention is still found in the kidneys, which might cause renal tubular damage. This latter aspect requires further clinical research to evaluate fully its effects. (author)

Structure-activity relationships of carbon-supported platinum-bismuth and platinum-antimony oxidation catalysts

CSIR Research Space (South Africa)

Maphoru, MV

2017-04-01

Full Text Available Compositional and morphological studies on supported platinum are important for the improvement and expanded use of catalysts for oxidative coupling reactions. Nanocomposites consisting of 5% Pt supported on activated carbon and promoted with 5% Bi...

An Immune Agent for Web-Based AI Course

Science.gov (United States)

Gong, Tao; Cai, Zixing

2006-01-01

To overcome weakness and faults of a web-based e-learning course such as Artificial Intelligence (AI), an immune agent was proposed, simulating a natural immune mechanism against a virus. The immune agent was built on the multi-dimension education agent model and immune algorithm. The web-based AI course was comprised of many files, such as HTML…

Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields)

International Nuclear Information System (INIS)

Kirson, Eilon D; Goldsher, Dorit; Wasserman, Yoram; Palti, Yoram; Schneiderman, Rosa S; Dbalý, Vladimír; Tovaryš, František; Vymazal, Josef; Itzhaki, Aviran; Mordechovich, Daniel; Gurvich, Zoya; Shmueli, Esther

2009-01-01

The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial. Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients. The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index ≤ 1). The sensitivity to chemotherapeutic treatment was increased by 1–3 orders of magnitude by adjuvant TTFields therapy (dose reduction indexes 23 – 1316). Similar findings were seen in an animal tumor model. Finally, 20 GBM patients were treated with TTFields for a median duration of 1 year. No TTFields related systemic toxicity was observed in any of these patients, nor was an increase in Temozolomide toxicity seen in patients receiving combined treatment. In newly diagnosed GBM patients, combining TTFields with Temozolomide treatment led to a progression free survival of 155 weeks and overall survival of 39+ months. These results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity

On the behavior of reduced graphene oxide based electrodes coated with dispersed platinum by alternate current methods in the electrochemical degradation of reactive dyes.

Science.gov (United States)

Del Río, A I; García, C; Molina, J; Fernández, J; Bonastre, J; Cases, F

2017-09-01

The electrochemical behavior of different carbon-based electrodes with and without nanoparticles of platinum electrochemically dispersed on their surface has been studied. Among others, reduced graphene oxide based electrodes was used to determine the best conditions for the decolorization/degradation of the reactive dye C.I. Reactive Orange 4 in sulfuric medium. Firstly, the electrochemical behavior was evaluated by cyclic voltammetry. Secondly, different electrolyses were performed using two cell configurations: cell with anodic and cathodic compartments separated (divided configuration) and without any separation (undivided configuration). The best results were obtained when reduced graphene oxide based anodes were used. The degree of decolorization was monitored by spectroscopic methods and high performance liquid chromatography. It was found that all of them followed pseudo-first order kinetics. When reduced graphene oxide-based electrodes coated with dispersed platinum by alternate current methods electrodes were used, the lowest energy consumption and the higher decolorization kinetics rate were obtained. Scanning Electronic Microscopy was used to observe the morphological surface differences. Copyright © 2017 Elsevier Ltd. All rights reserved.

MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1.

Science.gov (United States)

Qian, Lu; Zhang, Wanggang; Lei, Bo; He, Aili; Ye, Lianhong; Li, Xingzhou; Dong, Xin

2016-11-01

The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.

Maximum standard uptake value on pre-chemotherapeutic FDG-PET is a significant parameter for disease progression of newly diagnosed lymphoma

International Nuclear Information System (INIS)

Eo, Jae Seon; Lee, Won Woo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun

2005-01-01

F-18 FDG-PET is useful for detection and staging of lymphoma. We investigated the prognostic significance of maximum standard uptake (maxSUV) value of FDG-PET for newly diagnosed lymphoma patients before chemotherapy. Twenty-seven patients (male: female = 17: 10: age: 49±19 years) with newly diagnosed lymphoma were enrolled. Nine-teen patients suffered from B cell lymphoma, 6 Hodgkins disease and 2 T cell lymphoma. One patient was stage I, 9 stage II, 3 stage III, 1 stage IV and 13 others. All patients underwent FDG-PET before initiation of chemotherapy. MaxSUV values using lean body weight were obtained for main and largest lesion to represent maxSUV of the patients. The disease progression was defined as total change of the chemotherapeutic regimen or addition of new chemotherapeutic agent during follow up period. The observed period was 389±224 days. The value of maxSUV ranged from 3 to 18 (mean±SD = 10.6±4.4). The disease progressions occurred in 6 patients. Using Cox proportional-hazard regression analysis, maxSUV was identified as a significant parameter for the disease progression free survival (p=0.044). Kaplan-Meier survival curve analysis revealed that the group with higher maxSUV (=10.6, n=5) suffered from shorter disease progression free survival (median 299 days) than the group with lower maxSUV (<10.6, n = 22) (median 378 days, p=0.0146). We found that maxSUV on pre-chemotherapeutic F-18 FDG-PET for newly diagnosed lymphoma patients is a significant parameter for disease progression. Lymphoma patients can be stratified before initiation of chemotherapy in terms of disease progression by the value of maxSUV 10.6

Atomically flat platinum films grown on synthetic mica

Science.gov (United States)

Tanaka, Hiroyuki; Taniguchi, Masateru

2018-04-01

Atomically flat platinum thin films were heteroepitaxially grown on synthetic fluorophlogopite mica [KMg3(AlSi3O10)F2] by van der Waals epitaxy. Platinum films deposited on a fluorophlogopite mica substrate by inductively coupled plasma-assisted sputtering with oxygen introduction on a synthetic mica substrate resulted in the growth of twin single-crystalline epitaxial Pt(111) films.

Evaluating Water Demand Using Agent-Based Modeling

Science.gov (United States)

Lowry, T. S.

2004-12-01

The supply and demand of water resources are functions of complex, inter-related systems including hydrology, climate, demographics, economics, and policy. To assess the safety and sustainability of water resources, planners often rely on complex numerical models that relate some or all of these systems using mathematical abstractions. The accuracy of these models relies on how well the abstractions capture the true nature of the systems interactions. Typically, these abstractions are based on analyses of observations and/or experiments that account only for the statistical mean behavior of each system. This limits the approach in two important ways: 1) It cannot capture cross-system disruptive events, such as major drought, significant policy change, or terrorist attack, and 2) it cannot resolve sub-system level responses. To overcome these limitations, we are developing an agent-based water resources model that includes the systems of hydrology, climate, demographics, economics, and policy, to examine water demand during normal and extraordinary conditions. Agent-based modeling (ABM) develops functional relationships between systems by modeling the interaction between individuals (agents), who behave according to a probabilistic set of rules. ABM is a "bottom-up" modeling approach in that it defines macro-system behavior by modeling the micro-behavior of individual agents. While each agent's behavior is often simple and predictable, the aggregate behavior of all agents in each system can be complex, unpredictable, and different than behaviors observed in mean-behavior models. Furthermore, the ABM approach creates a virtual laboratory where the effects of policy changes and/or extraordinary events can be simulated. Our model, which is based on the demographics and hydrology of the Middle Rio Grande Basin in the state of New Mexico, includes agent groups of residential, agricultural, and industrial users. Each agent within each group determines its water usage

Bioaccumulation of platinum group metals in dolphins, Stenella sp ...

African Journals Online (AJOL)

Platinum group metals (PGMs) concentrations were measured in the tissues= of dolphins (Stenella sp.) caught along the Ghanaian coastline. Tissues from specimens caught by fishermen from Dixcove, western Ghana, were analysed in 2006 for palladium (Pd), platinum (Pt) and rhodium (Rh) using the Neutron Activation ...

A technology path to tactical agent-based modeling

Science.gov (United States)

James, Alex; Hanratty, Timothy P.

2017-05-01

Wargaming is a process of thinking through and visualizing events that could occur during a possible course of action. Over the past 200 years, wargaming has matured into a set of formalized processes. One area of growing interest is the application of agent-based modeling. Agent-based modeling and its additional supporting technologies has potential to introduce a third-generation wargaming capability to the Army, creating a positive overmatch decision-making capability. In its simplest form, agent-based modeling is a computational technique that helps the modeler understand and simulate how the "whole of a system" responds to change over time. It provides a decentralized method of looking at situations where individual agents are instantiated within an environment, interact with each other, and empowered to make their own decisions. However, this technology is not without its own risks and limitations. This paper explores a technology roadmap, identifying research topics that could realize agent-based modeling within a tactical wargaming context.

Cisplatin-Loaded Porous Si Microparticles Capped by Electroless Deposition of Platinum

Science.gov (United States)

Park, Jennifer S.; Kinsella, Joseph M.; Jandial, Danielle D.; Howell, Stephen B.

2012-01-01

The loading and release of the anti-cancer drug platinum cis-dichlorodiamine (cisplatin) from mesoporous silicon (pSi) microparticles is studied. The pSi microparticles are modified with 1-dodecene or with 1,12-undecylenic acid by hydrosilylation, and each modified pSi material acts as a reducing agent, forming a deposit of Pt on its surface that nucleates further deposition, capping the mesoporous structure and trapping free (unreduced) cisplatin within. Slow oxidation and hydrolytic dissolution of the Si/SiO2 matrix in buffer solution or in culture medium leads to the release of drugs from the microparticles. The drug-loaded particles show significantly greater toxicity toward human ovarian cancer cells (in vitro), relative to an equivalent quantity of free cisplatin. This result is consistent with the mechanism of drug release, which generates locally high concentrations of the drug in the vicinity of the degrading particles. Control assays with pSi particles loaded in a similar manner with the therapeutically inactive trans isomer of the platinum drug, and with pSi particles containing no drug, result in low cellular toxicity. A hydrophobic prodrug, cis,trans,cis-[Pt(NH3)2(O2C(CH2)8CH3)2Cl2], is loaded into the pSi films from chloroform without concomitant reduction of the pSi carrier. PMID:21630444

Root Canal Irrigation: Chemical Agents and Plant Extracts Against Enterococcus faecalis

Science.gov (United States)

Borzini, Letizia; Condò, Roberta; De Dominicis, Paolo; Casaglia, Adriano; Cerroni, Loredana

2016-01-01

Background: There are various microorganisms related to intra and extra-radicular infections and many of these are involved in persistent infections. Bacterial elimination from the root canal is achieved by means of the mechanical action of instruments and irrigation as well as the antibacterial effects of the irrigating solutions. Enterococcus faecalis can frequently be isolated from root canals in cases of failed root canal treatments. Antimicrobial agents have often been developed and optimized for their activity against endodontic bacteria. An ideal root canal irrigant should be biocompatible, because of its close contact with the periodontal tissues during endodontic treatment. Sodium hypoclorite (NaOCl) is one of the most widely recommended and used endodontic irrigants but it is highly toxic to periapical tissues. Objectives: To analyze the literature on the chemotherapeutic agent and plant extracts studied as root canal irrigants. In particularly, the study is focused on their effect on Enterococcus faecalis. Method: Literature search was performed electronically in PubMed (PubMed Central, MEDLINE) for articles published in English from 1982 to April 2015. The searched keywords were “endodontic irrigants” and “Enterococcus faecalis” and “essential oil” and “plant extracts”. Results: Many of the studied chemotherapeutic agents and plant extracts have shown promising results in vitro. Conclusion: Some of the considered phytotherapic substances, could be a potential alternative to NaOCl for the biomechanical treatment of the endodontic space. PMID:28217184

Analysis of damaged DNA / proteins interactions: Methodological optimizations and applications to DNA lesions induced by platinum anticancer drugs

International Nuclear Information System (INIS)

Bounaix Morand du Puch, Ch

2010-10-01

DNA lesions contribute to the alteration of DNA structure, thereby inhibiting essential cellular processes. Such alterations may be beneficial for chemotherapies, for example in the case of platinum anticancer agents. They generate bulky adducts that, if not repaired, ultimately cause apoptosis. A better understanding of the biological response to such molecules can be obtained through the study of proteins that directly interact with the damages. These proteins constitute the DNA lesions interactome. This thesis presents the development of tools aiming at increasing the list of platinum adduct-associated proteins. Firstly, we designed a ligand fishing system made of damaged plasmids immobilized onto magnetic beads. Three platinum drugs were selected for our study: cisplatin, oxali-platin and satra-platin. Following exposure of the trap to nuclear extracts from HeLa cancer cells and identification of retained proteins by proteomics, we obtained already known candidates (HMGB1, hUBF, FACT complex) but also 29 new members of the platinated-DNA interactome. Among them, we noted the presence of PNUTS, TOX4 and WDR82, which associate to form the recently-discovered PTW/PP complex. Their capture was then confirmed with a second model, namely breast cancer cell line MDA MB 231, and the biological consequences of such an interaction now need to be elucidated. Secondly, we adapted a SPRi bio-chip to the study of platinum-damaged DNA/proteins interactions. Affinity of HMGB1 and newly characterized TOX4 for adducts generated by our three platinum drugs could be validated thanks to the bio-chip. Finally, we used our tools, as well as analytical chemistry and biochemistry methods, to evaluate the role of DDB2 (a factor involved in the recognition of UV-induced lesions) in the repair of cisplatin adducts. Our experiments using MDA MB 231 cells differentially expressing DDB2 showed that this protein is not responsible for the repair of platinum damages. Instead, it appears to act

A hybrid agent-based approach for modeling microbiological systems.

Science.gov (United States)

Guo, Zaiyi; Sloot, Peter M A; Tay, Joc Cing

2008-11-21

Models for systems biology commonly adopt Differential Equations or Agent-Based modeling approaches for simulating the processes as a whole. Models based on differential equations presuppose phenomenological intracellular behavioral mechanisms, while models based on Multi-Agent approach often use directly translated, and quantitatively less precise if-then logical rule constructs. We propose an extendible systems model based on a hybrid agent-based approach where biological cells are modeled as individuals (agents) while molecules are represented by quantities. This hybridization in entity representation entails a combined modeling strategy with agent-based behavioral rules and differential equations, thereby balancing the requirements of extendible model granularity with computational tractability. We demonstrate the efficacy of this approach with models of chemotaxis involving an assay of 10(3) cells and 1.2x10(6) molecules. The model produces cell migration patterns that are comparable to laboratory observations.

Laboratory determination of chemotherapeutic drug resistance in tumor cells from patients with leukemia, using a fluorometric microculture cytotoxicity assay (FMCA).

Science.gov (United States)

Larsson, R; Kristensen, J; Sandberg, C; Nygren, P

1992-01-21

An automated fluorometric microculture cytotoxicity assay (FMCA) based on the measurement of fluorescence generated from cellular hydrolysis of fluorescein diacetate (FDA) to fluorescein was employed for chemotherapeutic-drug-sensitivity testing of tumor-cell suspensions from patients with leukemia. Fluorescence was linearly related to cell number, and reproducible measurements of drug sensitivity could be performed using fresh or cryopreserved leukemia cells. A marked heterogeneity with respect to chemotherapeutic drug sensitivity was observed for a panel of cytotoxic drugs tested in 43 samples from 35 patients with treated or untreated acute and chronic leukemia. For samples obtained from patients with chronic lymphocytic and acute myelocytic leukemia, sensitivity profiles for standard drugs corresponded to known clinical activity and the assay detected primary and acquired drug resistance. Individual in vitro/in vivo correlations indicated high specificity with respect to the identification of drug resistance. The results suggest that the FMCA may be a simple and rapid method for in vivo-representative determinations of chemotherapeutic drug resistance in tumor cells obtained from patients with leukemia.

On the enzymatic formation of platinum nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Govender, Y.; Riddin, T. L. [Rhodes University, Department of Biochemistry, Microbiology and Biotechnology (South Africa); Gericke, M. [MINTEK (South Africa); Whiteley, C. G., E-mail: C.Whiteley@ru.ac.z [Rhodes University, Department of Biochemistry, Microbiology and Biotechnology (South Africa)

2010-01-15

A dimeric hydrogenase enzyme (44.5 and 39.4 kDa sub units) was isolated in a 39.5% yield from the fungus Fusarium oxysporum and purified 4.64-fold by ion exchange chromatography on Sephacryl S-200. Characterisation of the enzyme afforded pH and temperature optima of 7.5 and 38 {sup o}C, respectively, a half-life stability of 36 min and a V{sub max} and K{sub m} of 3.57 nmol min{sup -1} mL{sup -1} and 2.25 mM, respectively. This enzyme was inhibited (non-competitively) by hydrogen hexachloroplatinic acid (H{sub 2}PtCl{sub 6}) at 1 or 2 mM with a K{sub i} value of 118 {mu}M. Incubation of the platinum salt with the pure enzyme under an atmosphere of hydrogen and optimum enzyme conditions (pH 7.5, 38 {sup o}C) afforded <10% bioreduction after 8 h while at conditions suitable for platinum nanoparticle formation (pH 9, 65 {sup o}C) over 90% reduction took place after the same length of time. Cell-free extract from the fungal isolates produced nearly 90% bioreduction of the platinum salt under both pH and temperature conditions. The bioreduction of the platinum salt by a hydrogenase enzyme takes place by a passive process and not an active one as previously understood.

Sum Frequency Generation Studies of Hydrogenation Reactions on Platinum Nanoparticles

Energy Technology Data Exchange (ETDEWEB)

Krier, James M. [Univ. of California, Berkeley, CA (United States)

2013-08-31

Sum Frequency Generation (SFG) vibrational spectroscopy is used to characterize intermediate species of hydrogenation reactions on the surface of platinum nanoparticle catalysts. In contrast to other spectroscopy techniques which operate in ultra-high vacuum or probe surface species after reaction, SFG collects information under normal conditions as the reaction is taking place. Several systems have been studied previously using SFG on single crystals, notably alkene hydrogenation on Pt(111). In this thesis, many aspects of SFG experiments on colloidal nanoparticles are explored for the first time. To address spectral interference by the capping agent (PVP), three procedures are proposed: UV cleaning, H2 induced disordering and calcination (core-shell nanoparticles). UV cleaning and calcination physically destroy organic capping while disordering reduces SFG signal through a reversible structural change by PVP.

Nanostructured gold and platinum electrodes on silicon structures for biosensing

International Nuclear Information System (INIS)

Ogurtsov, V I; Sheehan, M M

2005-01-01

Gold and platinum metal electrodes on Si/SiO 2 having undergone anisotropic potassium hydroxide (KOH) etch treatment are considered. This treatment etches at different rates and directions in the material resulting in creation of numerous pyramid shaped holes in the silicon substrate. This surface is used to make metal electrodes with increased electrode efficiency. The electrodes can serve as the sensors or as the sensor substrates (for surface polymer modification) and because both gold and platinum are inert they have applications for food safety biosensing. Wine, an economically significant food product, was chosen as a matrix, and impedance spectroscopy (EIS) was selected as a method of investigation of electrode behaviour. Based on results of EIS, different complexity equivalent circuits were determined by applying fitting mean square root optimisation of sensor complex impedance measurements

Towards Agent-Based Model Specification in Smart Grid: A Cognitive Agent-based Computing Approach

OpenAIRE

Akram, Waseem; Niazi, Muaz A.; Iantovics, Laszlo Barna

2017-01-01

A smart grid can be considered as a complex network where each node represents a generation unit or a consumer. Whereas links can be used to represent transmission lines. One way to study complex systems is by using the agent-based modeling (ABM) paradigm. An ABM is a way of representing a complex system of autonomous agents interacting with each other. Previously, a number of studies have been presented in the smart grid domain making use of the ABM paradigm. However, to the best of our know...

AT-406, an orally active antagonist of multiple inhibitor of apoptosis proteins, inhibits progression of human ovarian cancer.

Science.gov (United States)

Brunckhorst, Melissa K; Lerner, Dimitry; Wang, Shaomeng; Yu, Qin

2012-07-01

Ovarian carcinoma is the most deadly gynecological malignancy. Current chemotherapeutic drugs are only transiently effective and patients with advance disease often develop resistance despite significant initial responses. Mounting evidence suggests that anti-apoptotic proteins, including those of the inhibitor of apoptosis protein (IAP) family, play important roles in the chemoresistance. There has been a recent emergence of compounds that block the IAP functions. Here, we evaluated AT-406, a novel and orally active antagonist of multiple IAP proteins, in ovarian cancer cells as a single agent and in the combination with carboplatin for therapeutic efficacy and mechanism of action. We demonstrate that AT-406 has significant single agent activity in 60% of human ovarian cancer cell lines examined in vitro and inhibits ovarian cancer progression in vivo and that 3 out of 5 carboplatin-resistant cell lines are sensitive to AT-406, highlighting the therapeutic potential of AT-406 for patients with inherent or acquired platinum resistance. Additionally, our in vivo studies show that AT-406 enhances the carboplatin-induced ovarian cancer cell death and increases survival of the experimental mice, suggesting that AT-406 sensitizes the response of these cells to carboplatin. Mechanistically, we demonstrate that AT-406 induced apoptosis is correlated with its ability to down-regulate XIAP whereas AT-406 induces cIAP1 degradation in both AT-406 sensitive and resistance cell lines. Together, these results demonstrate, for the first time, the anti-ovarian cancer efficacy of AT-406 as a single agent and in the combination with carboplatin, suggesting that AT-406 has potential as a novel therapy for ovarian cancer patients, especially for patients exhibiting resistance to the platinum-based therapies.

Recent strikes in South Africa’s platinum-group metal mines: effects upon world platinum-group metal supplies

Science.gov (United States)

Yager, Thomas R.; Soto-Viruet, Yadira; Barry, James J.

2012-01-01

The recent labor disputes over wages and working conditions that have affected South Africa’s three leading platinum-group metal (PGM) producers have affected an industry already plagued by market pressures and labor unrest and raised the specter of constraints in the world’s supply of these metals. Although low demand for these metals in 2011 and 2012 helped to offset production losses of recent years, and particularly those losses caused by the strikes in 2012, a prolonged resumption of strikes could cause severe shortages of iridium, platinum, rhodium, ruthenium, and, to a lesser extent, palladium.

Novel insights in agent-based complex automated negotiation

CERN Document Server

Lopez-Carmona, Miguel; Ito, Takayuki; Zhang, Minjie; Bai, Quan; Fujita, Katsuhide

2014-01-01

This book focuses on all aspects of complex automated negotiations, which are studied in the field of autonomous agents and multi-agent systems. This book consists of two parts. I: Agent-Based Complex Automated Negotiations, and II: Automated Negotiation Agents Competition. The chapters in Part I are extended versions of papers presented at the 2012 international workshop on Agent-Based Complex Automated Negotiation (ACAN), after peer reviews by three Program Committee members. Part II examines in detail ANAC 2012 (The Third Automated Negotiating Agents Competition), in which automated agents that have different negotiation strategies and are implemented by different developers are automatically negotiated in the several negotiation domains. ANAC is an international competition in which automated negotiation strategies, submitted by a number of universities and research institutes across the world, are evaluated in tournament style. The purpose of the competition is to steer the research in the area of bilate...

Investigation of a combined platinum and electron lifetime control treatment for silicon

International Nuclear Information System (INIS)

Jia, Yunpeng; Cui, Zhihang; Yang, Fei; Zhao, Bao; Zou, Shikai; Liang, Yongsheng

2017-01-01

In silicon, the effect of Combined Lifetime Treatment (CLT) involving platinum diffusion and subsequent electron irradiation is different from the separate treatments of platinum diffusion and electron irradiation, even the treatment of electron irradiation followed by platinum diffusion. In this paper, we investigated the experimental behavior of different kinds of lifetime treated samples. We found that the reverse leakage current (I rr ) increases with the increasing platinum diffusion temperature or electron irradiation dose in the separate treatments. Conversely, I rr of the CLT samples decreased with rising platinum diffusion temperature at the same dose of subsequent electron irradiation. By deep-level transient spectroscopy (DLTS), a new energy level E7 (Ec −0.376 eV) was found in our CLT samples. The new level E7 suppresses the dominance of the deeper level E8 (Ec −0.476 eV), which is caused by electron irradiation directly and results in I rr ’s increase. The formation of the level E7 comes from the complex defect-combined effect between platinum atoms and silicon vacancies, and it affects device’s characteristics finally. These research will be helpful to the development of platinum-diffused devices used in intense electron irradiation environments.

Investigation of a combined platinum and electron lifetime control treatment for silicon

Energy Technology Data Exchange (ETDEWEB)

Jia, Yunpeng [College of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124 (China); Cui, Zhihang, E-mail: czhczh321321@126.com [College of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124 (China); Yang, Fei [State Grid Smart Electrical Engineering, Beijing 100192 (China); Zhao, Bao; Zou, Shikai; Liang, Yongsheng [College of Electronic Information and Control Engineering, Beijing University of Technology, Beijing 100124 (China)

2017-02-01

In silicon, the effect of Combined Lifetime Treatment (CLT) involving platinum diffusion and subsequent electron irradiation is different from the separate treatments of platinum diffusion and electron irradiation, even the treatment of electron irradiation followed by platinum diffusion. In this paper, we investigated the experimental behavior of different kinds of lifetime treated samples. We found that the reverse leakage current (I{sub rr}) increases with the increasing platinum diffusion temperature or electron irradiation dose in the separate treatments. Conversely, I{sub rr} of the CLT samples decreased with rising platinum diffusion temperature at the same dose of subsequent electron irradiation. By deep-level transient spectroscopy (DLTS), a new energy level E7 (Ec −0.376 eV) was found in our CLT samples. The new level E7 suppresses the dominance of the deeper level E8 (Ec −0.476 eV), which is caused by electron irradiation directly and results in I{sub rr}’s increase. The formation of the level E7 comes from the complex defect-combined effect between platinum atoms and silicon vacancies, and it affects device’s characteristics finally. These research will be helpful to the development of platinum-diffused devices used in intense electron irradiation environments.

Platinum nanoparticles: a non-toxic, effective and thermally stable alternative plasmonic material for cancer therapy and bioengineering.

Science.gov (United States)

Samadi, Akbar; Klingberg, Henrik; Jauffred, Liselotte; Kjær, Andreas; Bendix, Poul Martin; Oddershede, Lene B

2018-05-17

Absorption of near infrared (NIR) light by metallic nanoparticles can cause extreme heating and is of interest for instance in cancer treatment since NIR light has a relatively large penetration depth into biological tissue. Here, we quantify the extraordinary thermoplasmonic properties of platinum nanoparticles and demonstrate their efficiency in photothermal cancer therapy. Although platinum nanoparticles are extensively used for catalysis, they are much overlooked in a biological context. Via direct measurements based on a biological matrix we show that individual irradiated platinum nanoparticles with diameters of 50-70 nm can easily reach surface temperatures up to 900 K. In contrast to gold nanoshells, which are often used for photothermal purposes, we demonstrate that the platinum particles remain stable at these extreme temperatures. The experiments are paralleled by finite element modeling confirming the experimental results and establishing a theoretical understanding of the particles' thermoplasmonic properties. At extreme temperatures it is likely that a vapor layer will form around the plasmonic particle, and we show this scenario to be consistent with direct measurements and simulations. Viability studies demonstrate that platinum nanoparticles themselves are non-toxic at therapeutically relevant concentrations, however, upon laser irradiation we show that they efficiently kill human cancer cells. Therefore, platinum nanoparticles are highly promising candidates for thermoplasmonic applications in the life sciences, in nano-medicine, and for bio-medical engineering.

Agent-based Simulation of the Maritime Domain

Directory of Open Access Journals (Sweden)

O. Vaněk

2010-01-01

Full Text Available In this paper, a multi-agent based simulation platform is introduced that focuses on legitimate and illegitimate aspects of maritime traffic, mainly on intercontinental transport through piracy afflicted areas. The extensible architecture presented here comprises several modules controlling the simulation and the life-cycle of the agents, analyzing the simulation output and visualizing the entire simulated domain. The simulation control module is initialized by various configuration scenarios to simulate various real-world situations, such as a pirate ambush, coordinated transit through a transport corridor, or coastal fishing and local traffic. The environmental model provides a rich set of inputs for agents that use the geo-spatial data and the vessel operational characteristics for their reasoning. The agent behavior model based on finite state machines together with planning algorithms allows complex expression of agent behavior, so the resulting simulation output can serve as a substitution for real world data from the maritime domain.

Agent-Based Data Integration Framework

Directory of Open Access Journals (Sweden)

Łukasz Faber

2014-01-01

Full Text Available Combining data from diverse, heterogeneous sources while facilitating a unified access to it is an important (albeit difficult task. There are various possibilities of performing it. In this publication, we propose and describe an agent-based framework dedicated to acquiring and processing distributed, heterogeneous data collected from diverse sources (e.g., the Internet, external software, relational, and document databases. Using this multi-agent-based approach in the aspects of the general architecture (the organization and management of the framework, we create a proof-of-concept implementation. The approach is presented using a sample scenario in which the system is used to search for personal and professional profiles of scientists.

Platinum-Resistor Differential Temperature Sensor

Science.gov (United States)

Kolbly, R. B.; Britcliffe, M. J.

1985-01-01

Platinum resistance elements used in bridge circuit for measuring temperature difference between two flowing liquids. Temperature errors with circuit are less than 0.01 degrees C over range of 100 degrees C.

Determination of trace level of palladium and platinum content in anticancer drug Imatinib base by ICP-MS

International Nuclear Information System (INIS)

Yadav, Ravi; Salunke-Gawali, Sunita

2013-01-01

Metal impurities in Pharmaceutical drug substance is of great concern not only because of the intrinsic toxicity of certain contaminants but also due to the opposite effect that the contaminants which may have on drug stability and shelf life. Therefore it is necessary to monitor the organic as well as inorganic impurities throughout the process of manufacturing process at every stage from raw material, intermediate and finished products. An Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) method has been developed for Palladium and Platinum content in the anticancer drug, Imatinib mesylate. Rhodium (Rh) was used as internal standard for determination of Palladium and Platinum content on in Imatinib mesylate. (author)

Animal venoms as antimicrobial agents.

Science.gov (United States)

Perumal Samy, Ramar; Stiles, Bradley G; Franco, Octavio L; Sethi, Gautam; Lim, Lina H K

2017-06-15

Hospitals are breeding grounds for many life-threatening bacteria worldwide. Clinically associated gram-positive bacteria such as Staphylococcus aureus/methicillin-resistant S. aureus and many others increase the risk of severe mortality and morbidity. The failure of antibiotics to kill various pathogens due to bacterial resistance highlights the urgent need to develop novel, potent, and less toxic agents from natural sources against various infectious agents. Currently, several promising classes of natural molecules from snake (terrestrial and sea), scorpion, spider, honey bee and wasp venoms hold promise as rich sources of chemotherapeutics against infectious pathogens. Interestingly, snake venom-derived synthetic peptide/snake cathelicidin not only has potent antimicrobial and wound-repair activity but is highly stable and safe. Such molecules are promising candidates for novel venom-based drugs against S. aureus infections. The structure of animal venom proteins/peptides (cysteine rich) consists of hydrophobic α-helices or β-sheets that produce lethal pores and membrane-damaging effects on bacteria. All these antimicrobial peptides are under early experimental or pre-clinical stages of development. It is therefore important to employ novel tools for the design and the development of new antibiotics from the untapped animal venoms of snake, scorpion, and spider for treating resistant pathogens. To date, snail venom toxins have shown little antibiotic potency against human pathogens. Copyright © 2017 Elsevier Inc. All rights reserved.

New approaches in agent-based modeling of complex financial systems

Science.gov (United States)

Chen, Ting-Ting; Zheng, Bo; Li, Yan; Jiang, Xiong-Fei

2017-12-01

Agent-based modeling is a powerful simulation technique to understand the collective behavior and microscopic interaction in complex financial systems. Recently, the concept for determining the key parameters of agent-based models from empirical data instead of setting them artificially was suggested. We first review several agent-based models and the new approaches to determine the key model parameters from historical market data. Based on the agents' behaviors with heterogeneous personal preferences and interactions, these models are successful in explaining the microscopic origination of the temporal and spatial correlations of financial markets. We then present a novel paradigm combining big-data analysis with agent-based modeling. Specifically, from internet query and stock market data, we extract the information driving forces and develop an agent-based model to simulate the dynamic behaviors of complex financial systems.

Regorafenib overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter in colorectal cancer: In vitro and in vivo study.

Science.gov (United States)

Wang, Yi-Jun; Zhang, Yun-Kai; Zhang, Guan-Nan; Al Rihani, Sweilem B; Wei, Meng-Ning; Gupta, Pranav; Zhang, Xiao-Yu; Shukla, Suneet; Ambudkar, Suresh V; Kaddoumi, Amal; Shi, Zhi; Chen, Zhe-Sheng

2017-06-28

Chemotherapeutic multidrug resistance (MDR) is a significant challenge to overcome in clinic practice. Several mechanisms contribute to MDR, one of which is the augmented drug efflux induced by the upregulation of ABCB1 in cancer cells. Regorafenib, a multikinase inhibitor targeting the RAS/RAF/MEK/ERK pathway, was approved by the FDA to treat metastatic colorectal cancer and gastrointestinal stromal tumors. We investigated whether and how regorafenib overcame MDR mediated by ABCB1. The results showed that regorafenib reversed the ABCB1-mediated MDR and increased the accumulation of [ 3 H]-paclitaxel in ABCB1-overexpressing cells by suppressing efflux activity of ABCB1, but not altering expression level and localization of ABCB1. Regorafenib inhibited ATPase activity of ABCB1. In mice bearing resistant colorectal tumors, regorafenib raised the intratumoral concentration of paclitaxel and suppressed the growth of resistant colorectal tumors. But regorafenib did not induce cardiotoxicity/myelosuppression of paclitaxel in mice. Strategy to reposition one FDA-approved anticancer drug regorafenib to overcome the resistance of another FDA-approved, widely used chemotherapeutic paclitaxel, may be a promising direction for the field of adjuvant chemotherapy. This study provides clinical rationale for combination of conventional chemotherapy and targeted anticancer agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Platinum catalyst formed on carbon nanotube by the in-liquid plasma method for fuel cell

Energy Technology Data Exchange (ETDEWEB)

Show, Yoshiyuki; Hirai, Akira; Almowarai, Anas; Ueno, Yutaro

2015-12-01

In-liquid plasma was generated in the carbon nanotube (CNT) dispersion fluid using platinum electrodes. The generated plasma spattered the surface of the platinum electrodes and dispersed platinum particles into the CNT dispersion. Therefore, the platinum nanoparticles were successfully formed on the CNT surface in the dispersion. The platinum nanoparticles were applied to the proton exchange membrane fuel cell (PEMFC) as a catalyst. The electrical power of 108 mW/cm{sup 2} was observed from the fuel cell which was assembled with the platinum catalyst formed on the CNT by the in-liquid plasma method. - Highlights: • The platinum catalyst was successfully formed on the CNT surface in the dispersion by the in-liquid plasma method. • The electrical power of 108 mW/cm{sup 2} was observed from the fuel cell which was assembled with the platinum catalyst formed on the CNT by the in-liquid plasma method.

Efficient organic light-emitting devices with platinum-complex emissive layer

KAUST Repository

Yang, Xiaohui

2011-01-18

We report efficient organic light-emitting devices having a platinum-complex emissive layer with the peak external quantum efficiency of 17.5% and power efficiency of 45 lm W−1. Variation in the device performance with platinum-complex layer thickness can be attributed to the interplay between carrier recombination and intermolecular interactions in the layer. Efficient white devices using double platinum-complex layers show the external quantum efficiency of 10%, the Commission Internationale d’Énclairage coordinates of (0.42, 0.41), and color rendering index of 84 at 1000 cd m−2.

Efficient organic light-emitting devices with platinum-complex emissive layer

KAUST Repository

Yang, Xiaohui; Wu, Fang-Iy; Haverinen, Hanna; Li, Jian; Cheng, Chien-Hong; Jabbour, Ghassan E.

2011-01-01

We report efficient organic light-emitting devices having a platinum-complex emissive layer with the peak external quantum efficiency of 17.5% and power efficiency of 45 lm W−1. Variation in the device performance with platinum-complex layer thickness can be attributed to the interplay between carrier recombination and intermolecular interactions in the layer. Efficient white devices using double platinum-complex layers show the external quantum efficiency of 10%, the Commission Internationale d’Énclairage coordinates of (0.42, 0.41), and color rendering index of 84 at 1000 cd m−2.

Fabrication of platinum nanopillars on peptide-based soft structures using a focused ion beam

International Nuclear Information System (INIS)

Joshi, K B; Singh, Prabhpreet; Verma, Sandeep

2009-01-01

An expedient entry into the construction of bionanocomposites by merging peptide self-assembly, focused ion beam milling, and electron beam-induced deposition is described. Hexapeptides 1 and 2 revealed spherical self-assembled structures which are confirmed by a scanning electron microscope (SEM), atomic force microscope (AFM), focused ion beam/high-resolution scanning electron microscope (FIB-HRSEM), and high-resolution transmission electron microscopy (HRTEM). The microspheres from 1 and 2 are milled with the help of an ion beam to create different shapes. Soft spherical peptide-based structures were also subjected to fabrication under a gallium ion beam, followed by deposition of platinum pillars through a direct write process. It is envisaged that such hybrid bionanocomposites could have applications ranging from Pt-based hydrogenation catalysts to bioelectronics. In addition, such a fabrication process might also be useful to electrically connect two biological systems in order to study an electrical signal or electron transport phenomenon and structural transformations

Enzymatic recovery of platinum (IV) from industrial wastewater using ...

African Journals Online (AJOL)

highest hydrogen-dependent platinum (IV) reducing activity in the presence of hydrogenase and its physiological electron carrier, cytochrome c3. When the purified hydrogenase enzyme (with and without cytochrome c3) was used with the industrial effluent, containing 7.9 mg.l-1 platinum, only 10 – 15% recovery was noted ...

Chemotherapy in advanced ovarian cancer: four systematic meta-analyses of individual patient data from 37 randomized trials. Advanced Ovarian Cancer Trialists' Group.

Science.gov (United States)

Aabo, K.; Adams, M.; Adnitt, P.; Alberts, D. S.; Athanazziou, A.; Barley, V.; Bell, D. R.; Bianchi, U.; Bolis, G.; Brady, M. F.; Brodovsky, H. S.; Bruckner, H.; Buyse, M.; Canetta, R.; Chylak, V.; Cohen, C. J.; Colombo, N.; Conte, P. F.; Crowther, D.; Edmonson, J. H.; Gennatas, C.; Gilbey, E.; Gore, M.; Guthrie, D.; Yeap, B. Y.

1998-01-01

The purpose of this systematic study was to provide an up to date and reliable quantitative summary of the relative benefits of various types of chemotherapy (non-platinum vs platinum, single-agent vs combination and carboplatin vs cisplatin) in the treatment of advanced ovarian cancer. Also, to investigate whether well-defined patient subgroups benefit more or less from cisplatin- or carboplatin-based therapy. Meta-analyses were based on updated individual patient data from all available randomized controlled trials (published and unpublished), including 37 trials, 5667 patients and 4664 deaths. The results suggest that platinum-based chemotherapy is better than non-platinum therapy, show a trend in favour of platinum combinations over single-agent platinum, and suggest that cisplatin and carboplatin are equally effective. There is no good evidence that cisplatin is more or less effective than carboplatin in any particular subgroup of patients. Images Figure 1 Figure 2 Figure 3 PMID:9836481

An Interactive Tool for Creating Multi-Agent Systems and Interactive Agent-based Games

DEFF Research Database (Denmark)

Lund, Henrik Hautop; Pagliarini, Luigi

2011-01-01

Utilizing principles from parallel and distributed processing combined with inspiration from modular robotics, we developed the modular interactive tiles. As an educational tool, the modular interactive tiles facilitate the learning of multi-agent systems and interactive agent-based games...

Chemotherapeutic Impact Of Natural Antioxidant Flavonoids Gallic Acid Rutin Quercetin And Mannitol On Pathogenic Microbes And Their Synergistic Effect

Directory of Open Access Journals (Sweden)

Ganesh Ghosh

2015-08-01

Full Text Available Several studies suggest that natural flavonoids with antioxidants and can influence the response to chemotherapy as well as the development of adverse side effects that results from treatment with antineoplastic agents and Its prevalence over Multi drug resistant bacterial strain revived interest on Flavonoids. Synergistic effect is defined as passive interaction arises when two agents combine and together they exert an inhibitory effect that is greater than the sum of individual effect The new Synergistic therapy so that antioxidant are more effective in combination on multi drug resistant bacterial strain. Interaction between natural antioxidants and topoisomerase enzyme can be seen through Quercetin as a potent antimicrobial compound alone and in combination with other natural antioxidant like rutin. MICMBC result show antibacterial activity of the flavonoids were enhanced when used in combination against Staphylococcus aureus Bacillus cereus Bacillus subtilis Klebsiella pneumonae Escherichia coli as the test bacteria. The combination of rutin and quercetin rutin and gallic acid mannitol and gallic acid were much more effective than either flavonoid alone. Furthermore Its gave a good relation between these antioxidant compound and antimicrobial activity. Flavonoids as a chemotherapeutic agent and its Synergistic effect can be solution for various microbial disease conditions.

Validation of Agent Based Distillation Movement Algorithms

National Research Council Canada - National Science Library

Gill, Andrew

2003-01-01

Agent based distillations (ABD) are low-resolution abstract models, which can be used to explore questions associated with land combat operations in a short period of time Movement of agents within the EINSTein and MANA ABDs...

Prevalence and sunlight photolysis of controlled and chemotherapeutic drugs in aqueous environments

International Nuclear Information System (INIS)

Lin, Angela Yu-Chen; Lin, Yen-Ching; Lee, Wan-Ning

2014-01-01

This study addresses the occurrences and natural fates of chemotherapeutics and controlled drugs when found together in hospital effluents and surface waters. The results revealed the presence of 11 out of 16 drugs in hospital effluents, and the maximum detected concentrations were at the μg L −1 level in the hospital effluents and the ng L −1 level in surface waters. The highest concentrations corresponded to meperidine, morphine, 5-fluorouracil and cyclophosphamide. The sunlight photolysis of the target compounds was investigated, and the results indicated that morphine and codeine can be significantly attenuated, with half-lives of 0.27 and 2.5 h, respectively, in natural waters. Photolysis can lower the detected environmental concentrations, also lowering the estimated environmental risks of the target drugs to human health. Nevertheless, 5-fluorouracil and codeine were found to have a high risk quotient (RQ), demonstrating the high risks of directly releasing hospital wastewater into the environment. - Highlights: • High occurrence of chemotherapeutics and controlled substances in aqueous systems. • Photolysis lowers the detected concentrations of morphine and codeine. • 5-fluorouracil and codeine in hospital effluents have high risk quotients. - Chemotherapeutics and controlled drugs occur at significant levels in hospital effluents and surface waters. Natural sunlight photolysis reduces their environmental occurrence

Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy

DEFF Research Database (Denmark)

Krzakowski, Maciej; Ramlau, Rodryg; Jassem, Jacek

2010-01-01

To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy.......To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy....

Structural property of platinum mononitride

International Nuclear Information System (INIS)

Yu, L.H.; Yao, K.L.; Liu, Z.L.; Zhang, Y.S.

2007-01-01

The structural stability and pressure-induced structural phase transition of platinum mononitride (PtN), as well as its electronic structure, were studied using the full potential augmented plane wave plus local orbitals method with the generalized gradient approximation (GGA) exchange-correlation functional. The total energy calculations show that the optimized wurtzite structure is most stable energetically among four structures: zinc blende, rocksalt, CsCl and wurtzite, which reveals the platinum mononitride PtN perhaps crystallizes in the wurtzite structure; the pressure of phase transition from wurtzite to rocksalt is predicted to be 41.4 GPa.The calculated bulk modulus of the wurtzite structure is 99.41 GPa, which is smaller than that of the other three structures and face-centered cubic Pt. The band structure calculations show wurtzite PtN is metallic

The electron affinity of some radiotherapeutic agents used in cancer therapy

International Nuclear Information System (INIS)

Wold, E.; Kaalhus, O.; Johansen, E.S.; Ekse, A.T.

1980-01-01

In order to evaluate whether chemotherapeutic compounds applied in cancer treatment might interact with radiation as anoxic cell sensitizers, the electron-affinic properties of DTIC (5-(3,3-dimethyl-1-triazeno)imidazole-4 carboxamide) AIC 4(5)-aminoimidazole-5(4)-carboxamide, hydroxyurea, busulfan and cyclophosphamide were studied by pulse radiolysis. Reaction rates with hydrated electrons were determined for all these compounds. With the exception of DTIC, they all reacted much more slowly with electrons than do most electron-affinic sensitizers. One-electron reduction potentials were determined for DTIC, AIC and hydroxyurea. The values were all in the region for the onset of sensitization, with hydroxyurea as the most promising (E 7 1 = -0.552 V). For busulfan and cyclophosphamide no value could be determined, but these compounds are probably less electron-affinic than hydroxyurea. A possible application of chemotherapeutic agents as radiosensitizers is discussed. (author)

An Active Learning Exercise for Introducing Agent-Based Modeling

Science.gov (United States)

Pinder, Jonathan P.

2013-01-01

Recent developments in agent-based modeling as a method of systems analysis and optimization indicate that students in business analytics need an introduction to the terminology, concepts, and framework of agent-based modeling. This article presents an active learning exercise for MBA students in business analytics that demonstrates agent-based…

Efficacy Comparison of Six Chemotherapeutic Combinations for Osteosarcoma and Ewing's Sarcoma Treatment: A Network Meta-Analysis.

Science.gov (United States)

Zhang, Tao; Zhang, Song; Yang, Feifei; Wang, Lili; Zhu, Sigang; Qiu, Bing; Li, Shunhua; Deng, Zhongliang

2018-01-01

This study aimed to address the insufficiency of traditional meta-analysis and provide improved guidelines for the clinical practice of osteosarcoma treatment. The heterogeneity of the fixed-effect model was calculated, and when necessary, a random-effect model was adopted. Furthermore, the direct and indirect evidence was pooled together and exhibited in the forest plot and slash table. The surface under the cumulative ranking curve (SUCRA) value was also measured to rank each intervention. Finally, heat plot was introduced to demonstrate the contribution of each intervention and the inconsistency between direct and indirect comparisons. This network meta-analysis included 32 trials, involving a total of 5,626 subjects reported by 28 articles. All the treatments were classified into six chemotherapeutic combinations: dual agent with or without ifosfamide (IFO), multi-agent with or without IFO, and dual agent or multi-agent with IFO and etoposide. For the primary outcomes, both overall survival (OS) and event-free survival (EFS) rates were considered. The multi-agent integrated with IFO and etoposide showed an optimal performance for 5-year OS, 10-year OS, 3-year EFS, 5-year EFS, and 10-year EFS when compared with placebo. The SUCRA value of this treatment was also the highest of these six interventions. However, multi-drug with IFO alone had the highest SUCRA value of 0.652 and 0.516 when it came to relapse and lung-metastasis. It was efficient to some extent, but no significant difference was observed in both outcomes. Chemotherapy, applied as induction or adjuvant treatment with radiation therapy or surgery, is able to increase the survival rate of patients, especially by combining multi-drug with IFO and etoposide, which demonstrated the best performance in both OS and EFS. As for relapse and the lung-metastasis, multiple agents with IFO alone seemed to have the optimal efficiency, although no significant difference was observed here. J. Cell. Biochem. 119: 250

Tripodal osmium polypyridyl complexes for self-assembly on platinum nanoparticles

NARCIS (Netherlands)

Contreras-Carballada, P.; Edafe, F.; Tichelaar, F.D.; Belser, P.; De Cola, L.; Williams, R.M.

2011-01-01

The combination of platinum nanoparticles with a tripodal osmium complex that anchors to the metal surface leads, under visible light irradiation, to the formation of solvated electrons. The formation kinetics is limited by the detachment of the electron from the platinum surface into the solution,

Copper (II) complexes of bidentate ligands exhibit potent anti-cancer activity regardless of platinum sensitivity status.

Science.gov (United States)

Wehbe, Mohamed; Lo, Cody; Leung, Ada W Y; Dragowska, Wieslawa H; Ryan, Gemma M; Bally, Marcel B

2017-12-01

Insensitivity to platinum, either through inherent or acquired resistance, is a major clinical problem in the treatment of many solid tumors. Here, we explored the therapeutic potential of diethyldithiocarbamate (DDC), pyrithione (Pyr), plumbagin (Plum), 8-hydroxyquinoline (8-HQ), clioquinol (CQ) copper complexes in a panel of cancer cell lines that differ in their sensitivity to platins (cisplatin/carboplatin) using a high-content imaging system. Our data suggest that the copper complexes were effective against both platinum sensitive (IC 50  ~ 1 μM platinum) and insensitive (IC 50  > 5 μM platinum) cell lines. Furthermore, copper complexes of DDC, Pyr and 8-HQ had greater therapeutic activity compared to the copper-free ligands in all cell lines; whereas the copper-dependent activities of Plum and CQ were cell-line specific. Four of the copper complexes (Cu(DDC) 2 , Cu(Pyr) 2 , Cu(Plum) 2 and Cu(8-HQ) 2 ) showed IC 50 values less than that of cisplatin in all tested cell lines. The complex copper DDC (Cu(DDC) 2 ) was selected for in vivo evaluation due to its low nano-molar range activity in vitro and the availability of an injectable liposomal formulation. Liposomal (Cu(DDC) 2 ) was tested in a fast-growing platinum-resistant A2780-CP ovarian xenograft model and was found to achieve a statistically significant reduction (50%; p < 0.05) in tumour size. This work supports the potential use of copper-based therapeutics to treat cancers that are insensitive to platinum drugs.

Consentaneous agent-based and stochastic model of the financial markets.

Science.gov (United States)

Gontis, Vygintas; Kononovicius, Aleksejus

2014-01-01

We are looking for the agent-based treatment of the financial markets considering necessity to build bridges between microscopic, agent based, and macroscopic, phenomenological modeling. The acknowledgment that agent-based modeling framework, which may provide qualitative and quantitative understanding of the financial markets, is very ambiguous emphasizes the exceptional value of well defined analytically tractable agent systems. Herding as one of the behavior peculiarities considered in the behavioral finance is the main property of the agent interactions we deal with in this contribution. Looking for the consentaneous agent-based and macroscopic approach we combine two origins of the noise: exogenous one, related to the information flow, and endogenous one, arising form the complex stochastic dynamics of agents. As a result we propose a three state agent-based herding model of the financial markets. From this agent-based model we derive a set of stochastic differential equations, which describes underlying macroscopic dynamics of agent population and log price in the financial markets. The obtained solution is then subjected to the exogenous noise, which shapes instantaneous return fluctuations. We test both Gaussian and q-Gaussian noise as a source of the short term fluctuations. The resulting model of the return in the financial markets with the same set of parameters reproduces empirical probability and spectral densities of absolute return observed in New York, Warsaw and NASDAQ OMX Vilnius Stock Exchanges. Our result confirms the prevalent idea in behavioral finance that herding interactions may be dominant over agent rationality and contribute towards bubble formation.

Highly Luminescent Dinuclear Platinum(II) Complexes Incorporating Bis-Cyclometallating Pyrazine-Based Ligands: A Versatile Approach to Efficient Red Phosphors

OpenAIRE

Culham, Stacey; Lanoe, Pierre-Henri; Whittle, Victoria; Durrant, Marcus; Williams, Gareth; Kozhevnikov, Valery

2013-01-01

A series of luminescent dinuclear platinum(II) complexes incorporating diphenylpyrazine-based bridging ligands ((LH2)-H-n) has been prepared. Both 2,5-diphenylpyrazine ((LH2)-H-2) and 2,3-diphenylpyrazine ((LH2)-H-3) are able to undergo cyclometalation of the two phenyl rings, with each metal ion binding to the two nitrogen atoms of the central heterocycle, giving, after treatment with the anion of dipivaloyl methane (dpm), complexes of formula \\{Pt(dpm)\\}(2)L-n. These compounds are isomers o...

Modelling of robotic work cells using agent based-approach

Science.gov (United States)

Sękala, A.; Banaś, W.; Gwiazda, A.; Monica, Z.; Kost, G.; Hryniewicz, P.

2016-08-01

In the case of modern manufacturing systems the requirements, both according the scope and according characteristics of technical procedures are dynamically changing. This results in production system organization inability to keep up with changes in a market demand. Accordingly, there is a need for new design methods, characterized, on the one hand with a high efficiency and on the other with the adequate level of the generated organizational solutions. One of the tools that could be used for this purpose is the concept of agent systems. These systems are the tools of artificial intelligence. They allow assigning to agents the proper domains of procedures and knowledge so that they represent in a self-organizing system of an agent environment, components of a real system. The agent-based system for modelling robotic work cell should be designed taking into consideration many limitations considered with the characteristic of this production unit. It is possible to distinguish some grouped of structural components that constitute such a system. This confirms the structural complexity of a work cell as a specific production system. So it is necessary to develop agents depicting various aspects of the work cell structure. The main groups of agents that are used to model a robotic work cell should at least include next pattern representatives: machine tool agents, auxiliary equipment agents, robots agents, transport equipment agents, organizational agents as well as data and knowledge bases agents. In this way it is possible to create the holarchy of the agent-based system.

Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs

Directory of Open Access Journals (Sweden)

Braidwood L

2013-12-01

Full Text Available Lynne Braidwood,1 Sheila V Graham,2 Alex Graham,1 Joe Conner11Virttu Biologics Ltd, Department of Neurology, Southern General Hospital, Glasgow, UK; 2MRC-University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, Jarrett Building, University of Glasgow, Glasgow, UKAbstract: Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVexGM-CSF], is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with “standard-of-care” drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with “standard-of-care” drugs merits further investigation, both preclinically and in the clinic. Numerous publications report

Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase.

Science.gov (United States)

Shiraishi, A; Sakumi, K; Sekiguchi, M

2000-10-01

O(6)-methylguanine-DNA methyltransferase plays vital roles in preventing induction of mutations and cancer as well as cell death related to alkylating agents. Mice defective in the MGMT: gene, encoding the methyltransferase, were used to evaluate cell death-inducing and tumorigenic activities of therapeutic agents which have alkylation potential. MGMT(-/-) mice were considerably more sensitive to dacarbazine, a monofunctional triazene, than were wild-type mice, in terms of survival. When dacarbazine was administered i.p. to 6-week-old mice and survival at 30 days was enumerated, LD(50) values of MGMT(-/-) and MGMT(+/+) mice were 20 and 450 mg/kg body wt, respectively. Increased sensitivity of MGMT(-/-) mice to 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosou rea (ACNU), a bifunctional nitrosourea, was also noted. On the other hand, there was no difference in survival of MGMT(+/+) and MGMT(-/-) mice exposed to cyclophosphamide, a bifunctional nitrogen mustard. It appears that dacarbazine and ACNU produce O(6)-alkylguanine as a major toxic lesion, while cyclophosphamide yields other types of modifications in DNA which are not subjected to the action of the methyltransferase. MGMT(-/-) mice seem to be less refractory to the tumor-inducing effect of dacarbazine than are MGMT(+/+) mice. Thus, the level of O(6)-methylguanine-DNA methyltransferase activity is an important factor when determining susceptibility to drugs with the potential for alkylation.

Dissemination of Cultural Norms and Values: Agent-Based Modeling

Directory of Open Access Journals (Sweden)

Denis Andreevich Degterev

2016-12-01

Full Text Available This article shows how agent-based modeling allows us to explore the mechanisms of the dissemination of cultural norms and values both within one country and in the whole world. In recent years, this type of simulation is particularly prevalent in the analysis of international relations, becoming more popular than the system dynamics and discrete event simulation. The use of agent-based modeling in the analysis of international relations is connected with the agent-structure problem in international relations. Structure and agents act as interdependent and dynamically changing in the process of interaction between entities. Agent-structure interaction could be modeled by means of the theory of complex adaptive systems with the use of agent-based modeling techniques. One of the first examples of the use of agent-based modeling in political science is a model of racial segregation T. Shellinga. On the basis of this model, the author shows how the change in behavioral patterns at micro-level impacts on the macro-level. Patterns are changing due to the dynamics of cultural norms and values, formed by mass-media and other social institutes. The author shows the main areas of modern application of agent-based modeling in international studies including the analysis of ethnic conflicts, the formation of international coalitions. Particular attention is paid to Robert Axelrod approach based on the use of genetic algorithms to the spread of cultural norms and values. Agent-based modeling shows how to how to create such conditions that the norms that originally are not shared by a significant part of the population, eventually spread everywhere. Practical application of these algorithms is shown by the author of the article on the example of the situation in Ukraine in 2015-2016. The article also reveals the mechanisms of international spread of cultural norms and values. The main think-tanks using agent-based modeling in international studies are

Agent-based services for B2B electronic commerce

Science.gov (United States)

Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

2000-12-01

The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.

Science.gov (United States)

Yang, Jir-Jei; Yin, Jiu-Haw; Yang, Ding-I

2007-05-11

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of "GSNO>DEA/NO>SNP" when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Internet-enabled collaborative agent-based supply chains

Science.gov (United States)

Shen, Weiming; Kremer, Rob; Norrie, Douglas H.

2000-12-01

This paper presents some results of our recent research work related to the development of a new Collaborative Agent System Architecture (CASA) and an Infrastructure for Collaborative Agent Systems (ICAS). Initially being proposed as a general architecture for Internet based collaborative agent systems (particularly complex industrial collaborative agent systems), the proposed architecture is very suitable for managing the Internet enabled complex supply chain for a large manufacturing enterprise. The general collaborative agent system architecture with the basic communication and cooperation services, domain independent components, prototypes and mechanisms are described. Benefits of implementing Internet enabled supply chains with the proposed infrastructure are discussed. A case study on Internet enabled supply chain management is presented.

Agent-Based Models in Social Physics

Science.gov (United States)

Quang, Le Anh; Jung, Nam; Cho, Eun Sung; Choi, Jae Han; Lee, Jae Woo

2018-06-01

We review the agent-based models (ABM) on social physics including econophysics. The ABM consists of agent, system space, and external environment. The agent is autonomous and decides his/her behavior by interacting with the neighbors or the external environment with the rules of behavior. Agents are irrational because they have only limited information when they make decisions. They adapt using learning from past memories. Agents have various attributes and are heterogeneous. ABM is a non-equilibrium complex system that exhibits various emergence phenomena. The social complexity ABM describes human behavioral characteristics. In ABMs of econophysics, we introduce the Sugarscape model and the artificial market models. We review minority games and majority games in ABMs of game theory. Social flow ABM introduces crowding, evacuation, traffic congestion, and pedestrian dynamics. We also review ABM for opinion dynamics and voter model. We discuss features and advantages and disadvantages of Netlogo, Repast, Swarm, and Mason, which are representative platforms for implementing ABM.

Moral Guilt : An Agent-Based Model Analysis

OpenAIRE

Gaudou , Benoit; Lorini , Emiliano; Mayor , Eunate

2013-01-01

International audience; In this article we analyze the influence of a concrete moral emotion (i.e. moral guilt) on strategic decision making. We present a normal form Prisoner’s Dilemma with a moral component. We assume that agents evaluate the game’s outcomes with respect to their ideality degree (i.e. how much a given outcome conforms to the player’s moral values), based on two proposed notions on ethical preferences: Harsanyi’s and Rawls’. Based on such game, we construct and agent-based m...

Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

Science.gov (United States)

Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

2017-06-01

Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

Platinum single crystal electrodes for the electrocatalysis of methane oxidation

Directory of Open Access Journals (Sweden)

Mayara Munaretto

2011-03-01

Full Text Available The main objective of this paper is to characterize the voltammetric profiles of platinum single crystals of low Miller indexes Pt(100 and Pt(110 and study their catalytic activities on the oxidation of methane. In this way, it was developed a metallic surface modified by presence of other metal oxide, which presents catalytic activity for this reaction. It is well known that the electrooxidation of methane (CH4 leads mainly to the formation of CO2 and H2O, however, the oxidation can also lead to the formation of CO, a reaction intermediate that has strong interaction with metal surfaces, such as platinum. This molecule tends to accumulate on the platinum surface and to passive it, due to the self-poisoning, decreasing its catalytic activity. Therefore, the main aim of this work was the development of a platinum electrode modified by deposition of titanium oxide, which presented electrocatalytic properties for the oxidation of methane.

Liquid-liquid extraction/separation of platinum(IV) and rhodium(III) from acidic chloride solutions using tri-iso-octylamine

Energy Technology Data Exchange (ETDEWEB)

Lee, Jin-Young, E-mail: jinlee@kigam.re.kr [Metals Recovery Department, Minerals Resources Research Division, Korea Institute of Geoscience and Mineral Resources (KIGAM), 92 Gahangno, Yuesong-gu, Daejeon 305-350 (Korea, Republic of); Rajesh Kumar, J., E-mail: rajeshkumarphd@rediffmail.com [Metals Recovery Department, Minerals Resources Research Division, Korea Institute of Geoscience and Mineral Resources (KIGAM), 92 Gahangno, Yuesong-gu, Daejeon 305-350 (Korea, Republic of); Kim, Joon-Soo; Park, Hyung-Kyu; Yoon, Ho-Sung [Metals Recovery Department, Minerals Resources Research Division, Korea Institute of Geoscience and Mineral Resources (KIGAM), 92 Gahangno, Yuesong-gu, Daejeon 305-350 (Korea, Republic of)

2009-08-30

Liquid-liquid extraction/separation of platinum(IV) and rhodium(III) from acidic chloride solutions was carried out using tri-iso-octylamine (Alamine 308) as an extractant diluted in kerosene. The percentage extraction of platinum(IV) and rhodium(III) increased with increase in acid concentration up to 8 mol L{sup -1}. However, at 10 mol L{sup -1} HCl concentration, the extraction behavior was reversed, indicating the solvation type mechanism during extraction. The quantitative extraction of {approx}98% platinum(IV) and 36% rhodium(III) was achieved with 0.01 mol L{sup -1} Alamine 308. The highest separation factor (S.F. = 184.7) of platinum(IV) and rhodium(III) was achieved with 0.01 mol L{sup -1} Alamine 308 at 1.0 mol L{sup -1} of hydrochloric acid concentration. Alkaline metal salts like sodium chloride, sodium nitrate, sodium thiocyanate, lithium chloride, lithium nitrate, potassium chloride and potassium thiocyanate used for the salting-out effect. LiCl proved as best salt for the extraction of platinum(IV). Temperature effect demonstrates that the extraction process is exothermic. Hydrochloric acid and thiourea mixture proved to be better stripping reagents when compared with other mineral acids and bases.

Java-based mobile agent platforms for wireless sensor networks

NARCIS (Netherlands)

Aiello, F.; Carbone, A.; Fortino, G.; Galzarano, S.; Ganzha, M.; Paprzycki, M.

2010-01-01

This paper proposes an overview and comparison of mobile agent platforms for the development of wireless sensor network applications. In particular, the architecture, programming model and basic performance of two Java-based agent platforms, Mobile Agent Platform for Sun SPOT (MAPS) and Agent

Concentration and measuring Platinum Group Elements (PGE) Transfer Factor in soil and vegetations

International Nuclear Information System (INIS)

Adibah Sakinah Oyub

2012-01-01

This study was conducted to determine the concentration and to measure platinum group elements (PGE) transfer factor in environmental samples of roadside soil and vegetation. The use of vehicle catalytic converter has released platinum group elements (PGE) and other gases into the environment. Thus, roadside soil and plants were exposed to this element and has become the medium for the movement of this elements. Samples of roadside soil and vegetation were taken at various locations in UKM Bangi Toll and the concentration of platinum group elements (PGE) is determined using mass spectrometry-inductively coupled plasma (ICP-MS). Overall, the concentrations of platinum group elements (PGE), which is the element platinum (Pt) in soil was 0.016 ± 0.036 μgg -1 . While the concentration of the elements palladium (Pd) was 0.079 ± 0.019 μgg -1 and element rhodium (Rh) is at a concentration of 0.013 ± 0.020 μgg -1 . Overall, the transfer factor for the element platinum (Pt) is 1. While the transfer factor of the element palladium (Pd) is 0.96 and the element rhodium (Rh) is 1.11. In conclusion, the concentration of platinum group elements (PGE) in soils have increased. (author)

Platinum-Bismuth Bimetallic Catalysts: Synthesis, Characterization and Applications

OpenAIRE

Saucedo, Jose A, Jr; Xiao, Yang; Varma, Arvind

2015-01-01

Bimetallic catalysts have been explored and shown to exhibit unique characteristics which are not present in monometallic catalysts. Platinum is well known as an effective catalyst for oxidation and reduction reactions, and it can be made more effective when bismuth is introduced as a promotor. Thus, the effectiveness of the Pt-Bi catalyst was demonstrated in prior work. What is not clear, however, is the mechanism behind the catalyst function; why addition of bismuth to platinum decreases de...

Biosorption of platinum and palladium for their separation/preconcentration prior to graphite furnace atomic absorption spectrometric determination

Energy Technology Data Exchange (ETDEWEB)

Godlewska-Zylkiewicz, Beata E-mail: bgodlew@uwb.edu.pl

2003-08-15

Inexpensive baker's yeast Saccharomyces cerevisiae and green algae Chlorella vulgaris, either free or immobilized on silica gel have been shown to selectively accumulate platinum and palladium from water samples in acidic medium (pH 1.6-1.8). Optimization of conditions of metals biosorption (sample pH, algae and yeast masses, adsorption time, temperature) was performed in batch mode. The procedure of matrix separation based on biosorption of platinum and palladium on algae C. vulgaris covalently immobilized on silica gel in flow mode was developed. The use of algae in flow procedure offers several advantages compared with its use in the batch mode. The procedure shows better reproducibility (<2%), improved efficiency of platinum retention on the column (93.3{+-}1.6%), is less laborious and less time consuming. The best recovery of biosorbed metals from column (87.7{+-}3.3% for platinum and 96.8{+-}1.1 for palladium) was obtained with solution of 0.3 mol l{sup -1} thiourea in 1 mol l{sup -1} hydrochloric acid. The influence of thiourea on analytical signals of examined metals during GFAAS determination is discussed. The procedure has been applied for separation of noble metals from tap and waste water samples spiked with platinum and palladium.

Agent-based modeling and simulation Part 3 : desktop ABMS.

Energy Technology Data Exchange (ETDEWEB)