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Sample records for platinum 196 target

  1. PEPTIDE TARGETING OF PLATINUM ANTI-CANCER DRUGS

    PubMed Central

    Ndinguri, Margaret W.; Solipuram, Rajasree; Gambrell, Robert P.; Aggarwal, Sita; Hansel, William; Hammer, Robert P.

    2009-01-01

    Besides various side effects caused by platinum anticancer drugs, they are not efficiently absorbed by the tumor cells. Two Pt-peptide conjugates; cyclic mPeg-CNGRC-Pt (7) and cyclic mPeg-CNGRC-Pten (8) bearing the Asn-Gly-Arg (NGR) targeting sequence, a malonoyl linker and low molecular weight miniPEG groups have been synthesized. The platinum ligand was attached to the peptide via the carboxylic end of the malonate group at the end of the peptide. The pegylated peptide is non toxic and highly soluble in water. Platinum conjugates synthesized using the pegylated peptides are also water soluble with reduced or eliminated peptide immunogenicity. The choice of carboplatin as our untargeted platinum complex was due to the fact that malonate linker chelates platinum in a manner similar to carboplatin. Cell toxicity assay and competition assay on the PC-3 cells (CD13 positive receptors) revealed selective delivery and destruction of PC-3 cells using targeted Pt-peptide conjugates 7 and 8 significantly more than untargeted carboplatin. Platinum uptake on PC-3 cells was 12-fold more for conjugate 7 and 3-fold more for conjugate 8 compared to the untargeted carboplatin indicating selectively activation of the CD13 receptors and delivery of the conjugates to CD13 positive cells. Further analysis on effects of conjugates 7 and 8 on PC-3 cells using caspase-3/7, fluorescence microscopy and DNA fragmentation confirmed that the cells were dying by apoptosis. PMID:19775102

  2. EGFR-targeting peptide-coupled platinum(IV) complexes.

    PubMed

    Mayr, Josef; Hager, Sonja; Koblmüller, Bettina; Klose, Matthias H M; Holste, Katharina; Fischer, Britta; Pelivan, Karla; Berger, Walter; Heffeter, Petra; Kowol, Christian R; Keppler, Bernhard K

    2017-06-01

    The high mortality rate of lung cancer patients and the frequent occurrence of side effects during cancer therapy demonstrate the need for more selective and targeted drugs. An important and well-established target for lung cancer treatment is the occasionally mutated epidermal growth factor receptor (EGFR). As platinum(II) drugs are still the most important therapeutics against lung cancer, we synthesized in this study the first platinum(IV) complexes coupled to the EGFR-targeting peptide LARLLT (and the shuffled RTALLL as reference). Notably, HPLC-MS measurements revealed two different peaks with the same molecular mass, which turned out to be a transcyclization reaction in the linker between maleimide and the coupled cysteine moiety. With regard to the EGFR specificity, subsequent biological investigations (3-day viability, 14-day clonogenic assays and platinum uptake) on four different cell lines with different verified EGFR expression levels were performed. Unexpectedly, the results showed neither an enhanced activity nor an EGFR expression-dependent uptake of our new compounds. Consequently, fluorophore-coupled peptides were synthesized to re-evaluate the targeting ability of LARLLT itself. However, also with these molecules, flow cytometry measurements showed no correlation of drug uptake with the EGFR expression levels. Taken together, we successfully synthesized the first platinum(IV) complexes coupled to an EGFR-targeting peptide; however, the biological investigations revealed that LARLLT is not an appropriate peptide for enhancing the specific uptake of small-molecule drugs into EGFR-overexpressing cancer cells.

  3. Polyamide platinum anticancer complexes designed to target specific DNA sequences.

    PubMed

    Jaramillo, David; Wheate, Nial J; Ralph, Stephen F; Howard, Warren A; Tor, Yitzhak; Aldrich-Wright, Janice R

    2006-07-24

    Two new platinum complexes, trans-chlorodiammine[N-(2-aminoethyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-2) and trans-chlorodiammine[N-(6-aminohexyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-6) have been synthesized as proof-of-concept molecules in the design of agents that can specifically target genes in DNA. Coordinate covalent binding to DNA was demonstrated with electrospray ionization mass spectrometry. Using circular dichroism, these complexes were found to show greater DNA binding affinity to the target sequence: d(CATTGTCAGAC)(2), than toward either d(GTCTGTCAATG)(2,) which contains different flanking sequences, or d(CATTGAGAGAC)(2), which contains a double base pair mismatch sequence. DJ1953-2 unwinds the DNA helix by around 13 degrees , but neither metal complex significantly affects the DNA melting temperature. Unlike simple DNA minor groove binders, DJ1953-2 is able to inhibit, in vitro, RNA synthesis. The cytotoxicity of both metal complexes in the L1210 murine leukaemia cell line was also determined, with DJ1953-6 (34 microM) more active than DJ1953-2 (>50 microM). These results demonstrate the potential of polyamide platinum complexes and provide the structural basis for designer agents that are able to recognize biologically relevant sequences and prevent DNA transcription and replication.

  4. Biotinylated Platinum(II) Ferrocenylterpyridine Complexes for Targeted Photoinduced Cytotoxicity.

    PubMed

    Mitra, Koushambi; Shettar, Abhijith; Kondaiah, Paturu; Chakravarty, Akhil R

    2016-06-06

    Biotinylated platinum(II) ferrocenylterpyridine (Fc-tpy) complexes [Pt(Fc-tpy)(L(1))]Cl (1) and [Pt(Fc-tpy)(L(2))]Cl (2), where HL(1) and HL(2) are biotin-containing ligands, were prepared, and their targeted photoinduced cytotoxic effect in cancer cells over normal cells was studied. A nonbiotinylated complex, [Pt(Fc-tpy)(L(3))]Cl (3), was prepared as a control to study the role of the biotin moiety in cellular uptake properties of the complexes. Three platinum(II) phenylterpyridine (Ph-tpy) complexes, viz., [Pt(Ph-tpy)(L(1))]Cl (4), [Pt(Ph-tpy)(L(2))]Cl (5), and [Pt(Ph-tpy)(L(3))]Cl (6), were synthesized and explored to understand the role of a metal-bound Fc-tpy ligand over Ph-tpy as a photoinitiator. The Fc-tpy complexes displayed an intense absorption band near 640 nm, which was absent in their Ph-tpy analogues. The Fc-tpy complexes (1 mM in 0.1 M TBAP) showed an irreversible cyclic voltammetric anodic response of the Fc/Fc(+) couple near 0.25 V. The Fc-tpy complexes displayed photodegradation in red light of 647 nm involving the formation of a ferrocenium ion (Fc(+)) and reactive oxygen species (ROS). Photoinduced release of the biotinylated ligands was observed from spectral measurements, and this possibly led to the controlled generation of an active platinum(II) species, which binds to the calf-thymus DNA used for this study. The biotinylated photoactive Fc-tpy complexes showed significant photoinduced cytotoxicity, giving a IC50 value of ∼7 μM in visible light of 400-700 nm with selective uptake in BT474 cancer cells over HBL-100 normal cells. Furthermore, ferrocenyl complexes resulted in light-induced ROS-mediated apoptosis, as indicated by DCFDA, annexin V/FITC staining, and sub-G1 DNA content determined by fluorescent activated cell sorting analysis. The phenyl analogues 4 and 5 were photostable, served as DNA intercalators, and demonstrated selective cytotoxicity in the cancer cells, giving IC50 values of ∼4 μM.

  5. MicroRNA-196a Is a Putative Diagnostic Biomarker and Therapeutic Target for Laryngeal Cancer

    PubMed Central

    Saito, Koichiro; Inagaki, Koji; Kamimoto, Takahiro; Ito, Yoko; Sugita, Toshiaki; Nakajo, Satoko; Hirasawa, Akira; Iwamaru, Arifumi; Ishikura, Takashi; Hanaoka, Hideki; Okubo, Keisuke; Onozaki, Tokio; Zama, Takeru

    2013-01-01

    Background MicroRNA (miRNA) is an emerging subclass of small non-coding RNAs that regulates gene expression and has a pivotal role for many physiological processes including cancer development. Recent reports revealed the role of miRNAs as ideal biomarkers and therapeutic targets due to their tissue- or disease-specific nature. Head and neck cancer (HNC) is a major cause of cancer-related mortality and morbidity, and laryngeal cancer has the highest incidence in it. However, the molecular mechanisms involved in laryngeal cancer development remain to be known and highly sensitive biomarkers and novel promising therapy is necessary. Methodology/Principal Findings To explore laryngeal cancer-specific miRNAs, RNA from 5 laryngeal surgical specimens including cancer and non-cancer tissues were hybridized to microarray carrying 723 human miRNAs. The resultant differentially expressed miRNAs were further tested by using quantitative real time PCR (qRT-PCR) on 43 laryngeal tissue samples including cancers, noncancerous counterparts, benign diseases and precancerous dysplasias. Significant expressional differences between matched pairs were reproduced in miR-133b, miR-455-5p, and miR-196a, among which miR-196a being the most promising cancer biomarker as validated by qRT-PCR analyses on additional 84 tissue samples. Deep sequencing analysis revealed both quantitative and qualitative deviation of miR-196a isomiR expression in laryngeal cancer. In situ hybridization confirmed laryngeal cancer-specific expression of miR-196a in both cancer and cancer stroma cells. Finally, inhibition of miR-196a counteracted cancer cell proliferation in both laryngeal cancer-derived cells and mouse xenograft model. Conclusions/Significance Our study provided the possibilities that miR-196a might be very useful in diagnosing and treating laryngeal cancer. PMID:23967217

  6. Targeting Notch, a key pathway for ovarian cancer stem cells, sensitizes tumors to platinum therapy.

    PubMed

    McAuliffe, Shannon M; Morgan, Stefanie L; Wyant, Gregory A; Tran, Lieu T; Muto, Katherine W; Chen, Yu Sarah; Chin, Kenneth T; Partridge, Justin C; Poole, Barish B; Cheng, Kuang-Hung; Daggett, John; Cullen, Kristen; Kantoff, Emily; Hasselbatt, Kathleen; Berkowitz, Julia; Muto, Michael G; Berkowitz, Ross S; Aster, Jon C; Matulonis, Ursula A; Dinulescu, Daniela M

    2012-10-23

    Chemoresistance to platinum therapy is a major obstacle that needs to be overcome in the treatment of ovarian cancer patients. The high rates and patterns of therapeutic failure seen in patients are consistent with a steady accumulation of drug-resistant cancer stem cells (CSCs). This study demonstrates that the Notch signaling pathway and Notch3 in particular are critical for the regulation of CSCs and tumor resistance to platinum. We show that Notch3 overexpression in tumor cells results in expansion of CSCs and increased platinum chemoresistance. In contrast, γ-secretase inhibitor (GSI), a Notch pathway inhibitor, depletes CSCs and increases tumor sensitivity to platinum. Similarly, a Notch3 siRNA knockdown increases the response to platinum therapy, further demonstrating that modulation of tumor chemosensitivity by GSI is Notch specific. Most importantly, the cisplatin/GSI combination is the only treatment that effectively eliminates both CSCs and the bulk of tumor cells, indicating that a dual combination targeting both populations is needed for tumor eradication. In addition, we found that the cisplatin/GSI combination therapy has a synergistic cytotoxic effect in Notch-dependent tumor cells by enhancing the DNA-damage response, G(2)/M cell-cycle arrest, and apoptosis. Based on these results, we conclude that targeting the Notch pathway could significantly increase tumor sensitivity to platinum therapy. Our study suggests important clinical applications for targeting Notch as part of novel treatment strategies upon diagnosis of ovarian cancer and at recurrence. Both platinum-resistant and platinum-sensitive relapses may benefit from such an approach as clinical data suggest that all relapses after platinum therapy are increasingly platinum resistant.

  7. miR-196a targets netrin 4 and regulates cell proliferation and migration of cervical cancer cells

    SciTech Connect

    Zhang, Jie; Zheng, Fangxia; Yu, Gang; Yin, Yanhua; Lu, Qingyang

    2013-11-01

    Highlights: •miR-196a was overexpressed in cervical cancer tissue compared to normal tissue. •miR-196a expression elevated proliferation and migration of cervical cancer cells. •miR-196a inhibited NTN4 expression by binding 3′-UTR region of NTN4 mRNA. •NTN4 inversely correlated with miR-196a expression in cervical tissue and cell line. •NTN4 expression was low in cervical cancer tissue compared to normal tissue. -- Abstract: Recent research has uncovered tumor-suppressive and oncogenic potential of miR-196a in various tumors. However, the expression and mechanism of its function in cervical cancer remains unclear. In this study, we assess relative expression of miR-196a in cervical premalignant lesions, cervical cancer tissues, and four cancer cell lines using quantitative real-time PCR. CaSki and HeLa cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cancer cell proliferation and migration. We demonstrated that miR-196a was overexpressed in cervical intraepithelial neoplasia 2–3 and cervical cancer tissue. Moreover, its expression contributes to the proliferation and migration of cervical cancer cells, whereas inhibiting its expression led to a reduction in proliferation and migration. Five candidate targets of miR-196a chosen by computational prediction and Cervical Cancer Gene Database search were measured for their mRNA in both miR-196a-overexpressing and -depleted cancer cells. Only netrin 4 (NTN4) expression displayed an inverse association with miR-196a. Fluorescent reporter assays revealed that miR-196a inhibited NTN4 expression by targeting one binding site in the 3′-untranslated region (3′-UTR) of NTN4 mRNA. Furthermore, qPCR and Western blot assays verified NTN4 expression was downregulated in cervical cancer tissues compared to normal controls, and in vivo mRNA level of NTN4 inversely correlated with miR-196a expression. In summary, our findings provide new insights about the

  8. MicroRNA-196a/b Mitigate Renal Fibrosis by Targeting TGF-β Receptor 2.

    PubMed

    Meng, Jiao; Li, Limin; Zhao, Yue; Zhou, Zhen; Zhang, Mingchao; Li, Donghai; Zhang, Chen-Yu; Zen, Ke; Liu, Zhihong

    2016-10-01

    Organ-specific microRNAs have essential roles in maintaining normal organ function. However, the microRNA profile of the kidney and the role of microRNAs in modulating renal function remain undefined. We performed an unbiased assessment of the genome-wide microRNA expression profile in 14 mouse organs using Solexa deep sequencing and found that microRNA-196a (miR-196a) and miR-196b are selectively expressed in kidney, with 74.37% of mouse total miR-196a and 73.19% of mouse total miR-196b distributed in the kidneys. We confirmed the predominant expression of miR-196a/b in mouse and human kidney, particularly in the glomeruli and tubular epithelium, by quantitative RT-PCR and in situ hybridization assays. During unilateral ureteral obstruction (UUO)-induced mouse renal fibrosis, renal miR-196a/b levels rapidly decreased. Elevation of renal miR-196a/b expression by hydrodynamic-based delivery of a miR-196a/b-expressing plasmid before or shortly after UUO significantly downregulated profibrotic proteins, including collagen 1 and α-smooth muscle actin, and mitigated UUO-induced renal fibrosis. In contrast, depletion of renal miR-196a/b by miR-196a/b antagomirs substantially aggravated UUO-induced renal fibrosis. Mechanistic studies further identified transforming growth factor beta receptor II (TGFβR2) as a common target of miR-196a and miR-196b. Decreasing miR-196a/b expression in human HK2 cells strongly activated TGF-β-Smad signaling and cell fibrosis; whereas increasing miR-196a/b levels in mouse primary cultured tubular epithelial cells inhibited TGF-β-Smad signaling. In the UUO model, miR-196a/b silenced TGF-β-Smad signaling, decreased the expression of collagen 1 and α-smooth muscle actin, and attenuated renal fibrosis. Our findings suggest that elevating renal miR-196a/b levels may be a novel therapeutic strategy for treating renal fibrosis. Copyright © 2016 by the American Society of Nephrology.

  9. Laser ablation of a platinum target in water. III. Laser-induced reactions

    NASA Astrophysics Data System (ADS)

    Nichols, William T.; Sasaki, Takeshi; Koshizaki, Naoto

    2006-12-01

    This is the third paper in our series studying the laser-target-liquid interactions occurring in laser ablation in liquids (LAL). Here, laser ablation of a platinum target in pure water at 355nm wavelength is studied as a function of laser energy. We describe three distinct reaction regimes between the ablated target species and water at different laser focusing conditions. At low laser fluence (<10J/cm2), material removal is caused by laser heating of the platinum surface and the primary products are small clusters with a large percentage of platinum atoms in a nonzero oxidation state. At intermediate fluences (10-70J/cm2), platinum nanoparticles are the primary products. Our previous studies demonstrated that in this fluence regime ablation occurs through both thermal vaporization and explosive ejection of molten droplets. In both cases reactivity is small due to the low reactivity of platinum with water. At high fluences (>70J/cm2), we find large, faceted particles that are attributed to the drying of PtOx gels formed by reactive plasma etching of the target. Taken together these results demonstrate that significant tunability in the target-liquid interaction is possible during nanomaterial synthesis by LAL.

  10. Combination Platinum-based and DNA Damage Response-targeting Cancer Therapy: Evolution and Future Directions.

    PubMed

    Basourakos, Spyridon P; Li, Likun; Aparicio, Ana M; Corn, Paul G; Kim, Jeri; Thompson, Timothy C

    2017-01-01

    Maintenance of genomic stability is a critical determinant of cell survival and is necessary for growth and progression of malignant cells. Interstrand crosslinking (ICL) agents, including platinum-based agents, are first-line chemotherapy treatment for many solid human cancers. In malignant cells, ICL triggers the DNA damage response (DDR). When the damage burden is high and lesions cannot be repaired, malignant cells are unable to divide and ultimately undergo cell death either through mitotic catastrophe or apoptosis. The activities of ICL agents, in particular platinum-based therapies, establish a "molecular landscape," i.e., a pattern of DNA damage that can potentially be further exploited therapeutically with DDR-targeting agents. If the molecular landscape created by platinum-based agents could be better defined at the molecular level, a systematic, mechanistic rationale(s) could be developed for the use of DDR-targeting therapies in combination/maintenance protocols for specific, clinically advanced malignancies. New therapeutic drugs such as poly(ADP-ribose) polymerase (PARP) inhibitors are examples of DDR-targeting therapies that could potentially increase the DNA damage and replication stress imposed by platinum-based agents in tumor cells and provide therapeutic benefit for patients with advanced malignancies. Recent studies have shown that the use of PARP inhibitors together with platinum-based agents is a promising therapy strategy for ovarian cancer patients with "BRCAness", i.e., a phenotypic characteristic of tumors that not only can involve loss-of-function mutations in either BRCA1 or BRCA2, but also encompasses the molecular features of BRCA-mutant tumors. On the basis of these promising results, additional mechanism-based studies focused on the use of various DDR-targeting therapies in combination with platinum-based agents should be considered. This review discusses, in general, (1) ICL agents, primarily platinum-based agents, that establish a

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

    PubMed

    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.

  12. 2-Deoxyglucose conjugated platinum (II) complexes for targeted therapy: design, synthesis, and antitumor activity.

    PubMed

    Mi, Qian; Ma, Yuru; Gao, Xiangqian; Liu, Ran; Liu, Pengxing; Mi, Yi; Fu, Xuegang; Gao, Qingzhi

    2016-11-01

    Malignant neoplasms exhibit an elevated rate of glycolysis over normal cells. To target the Warburg effect, we designed a new series of 2-deoxyglucose (2-DG) conjugated platinum (II) complexes for glucose transporter 1 (GLUT1)-mediated anticancer drug delivery. The potential GLUT1 transportability of the complexes was investigated through a comparative molecular docking analysis utilizing the latest GLUT1 protein crystal structure. The key binding site for 2-DG as GLUT1's substrate was identified with molecular dynamics simulation, and the docking study demonstrated that the 2-DG conjugated platinum (II) complexes can be recognized by the same binding site as potential GLUT1 substrate. The conjugates were synthesized and evaluated for in vitro cytotoxicity study with seven human cancer cell lines. The results of this study revealed that 2-DG conjugated platinum (II) complexes are GLUT1 transportable substrates and exhibit improved cytotoxicities in cancer cell lines that over express GLUT1 when compared to the clinical drug, Oxaliplatin. The correlation between GLUT1 expression and antitumor effects are also confirmed. The study provides fundamental information supporting the potential of the 2-DG conjugated platinum (II) complexes as lead compounds for further pharmaceutical R&D.

  13. Reversing Platinum Resistance in High-Grade Serous Ovarian Carcinoma: Targeting BRCA and the Homologous Recombination System.

    PubMed

    Wiedemeyer, W Ruprecht; Beach, Jessica A; Karlan, Beth Y

    2014-01-01

    Resistance to platinum chemotherapy is one of the main factors driving ovarian cancer mortality, and overcoming platinum resistance is considered one of the greatest challenges in ovarian cancer research. Genetic and functional evidence points to the homologous recombination (HR) DNA repair system, and BRCA1 and BRCA2 in particular, as main determinants of response to platinum therapy. BRCA-mutant ovarian cancers are especially sensitive to platinum, associated with better survival, and amenable to poly ADP ribose polymerase inhibitor treatment. Here, we discuss a therapeutic concept that seeks to disrupt HR capacity via targeting of BRCA1 and BRCA2 functionality in order to reverse platinum resistance in BRCA-proficient high-grade serous ovarian cancers (HGSOC). We review the molecular signaling pathways that converge on BRCA1 and BRCA2, their activation status in ovarian cancer, and therapeutic options to modulate BRCA function. Several recent publications demonstrate efficient chemosensitization of BRCA-proficient cancers by combining targeted therapy with standard platinum-based agents. Due to its inherent genomic heterogeneity, molecularly defined subgroups of HGSOC may require different approaches. We seek to provide an overview of available agents and their potential use to reverse platinum resistance by inhibiting the HR system, either directly or indirectly, by targeting oncogenic activators of HR.

  14. Development of EGFR Targeted Nanoemulsion for Imaging and Novel Platinum Therapy of Ovarian Cancer

    PubMed Central

    Ganta, Srinivas; Singh, Amit; Patel, Niravkumar R.; Cacaccio, Joseph; Rawal, Yashesh H.; Davis, Barbara J.; Amiji, Mansoor M.; Coleman, Timothy P.

    2014-01-01

    Purpose Platinum-based chemotherapy is the treatment of choice for malignant epithelial ovarian cancers, but generalized toxicity and platinum resistance limits its use. Theranostic nanoemulsion with a novel platinum prodrug, myrisplatin, and the pro-apoptotic agent, C6-ceramide, were designed to overcome these limitations. Methods The nanoemulsions, including ones with an EGFR binding peptide and gadolinium, were made using generally regarded as safe grade excipients and a high shear microfluidization process. Efficacy was evaluated in ovarian cancer cells, SKOV3, A2780 and A2780CP. Results The nanoemulsion with particle size <150 nm were stable in plasma and parenteral fluids for 24 h. Ovarian cancer cells in vitro efficiently took up the non-targeted and EGFR-targeted nanoemulsions; improved cytotoxicity was observed for the these nanoemulsions with the latter showing a 50-fold drop in the IC50 in SKOV3 cells as compared to cisplatin alone. The addition of gadolinium did not affect cell viability in vitro, but showed relaxation times comparable to Magnevist®. Conclusion The myrisplatin/C6-ceramide nanoemulsion synergistically enhanced in vitro cytotoxicity. An EGFR binding peptide addition further increased in vitro cytotoxicity in EGFR positive cancer cells. The diagnostic version showed MR imaging similar to the clinically relevant Magnevist® and may be suitable as a theranostic for ovarian cancer. PMID:24643932

  15. Personalized medicine for targeted and platinum-based chemotherapy of lung and bladder cancer

    PubMed Central

    Cimino, George D; Pan, Chong-xian; Henderson, Paul T

    2013-01-01

    The personalized medicine revolution is occurring for cancer chemotherapy. Biomarkers are increasingly capable of distinguishing genotypic or phenotypic traits of individual tumors, and are being linked to the selection of treatment protocols. This review covers the molecular basis for biomarkers of response to targeted and cytotoxic lung and bladder cancer treatment with an emphasis on platinum-based chemotherapy. Platinum derivatives are a class of drugs commonly employed against solid tumors that kill cells by covalent attachment to DNA. Platinum–DNA adduct levels in patient tissues have been correlated to response and survival. The sensitivity and precision of adduct detection has increased to the point of enabling subtherapeutic dosing for diagnostics applications, termed diagnostic microdosing, prior to the initiation of full-dose therapy. The clinical status of this unique phenotypic marker for lung and bladder cancer applications is detailed along with discussion of future applications. PMID:23394702

  16. Targeting c-MYC in Platinum-Resistant Ovarian Cancer.

    PubMed

    Reyes-González, Jeyshka M; Armaiz-Peña, Guillermo N; Mangala, Lingegowda S; Valiyeva, Fatma; Ivan, Cristina; Pradeep, Sunila; Echevarría-Vargas, Ileabett M; Rivera-Reyes, Adrian; Sood, Anil K; Vivas-Mejía, Pablo E

    2015-10-01

    The purpose of this study was to investigate the molecular and therapeutic effects of siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer. Statistical analysis of patient's data extracted from The Cancer Genome Atlas (TCGA) portal showed that the disease-free (DFS) and the overall (OS) survival were decreased in ovarian cancer patients with high c-MYC mRNA levels. Furthermore, analysis of a panel of ovarian cancer cell lines showed that c-MYC protein levels were higher in cisplatin-resistant cells when compared with their cisplatin-sensitive counterparts. In vitro cell viability, growth, cell-cycle progression, and apoptosis, as well as in vivo therapeutic effectiveness in murine xenograft models, were also assessed following siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer cells. Significant inhibition of cell growth and viability, cell-cycle arrest, and activation of apoptosis were observed upon siRNA-mediated c-MYC depletion. In addition, single weekly doses of c-MYC-siRNA incorporated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000)-based nanoliposomes resulted in significant reduction in tumor growth. These findings identify c-MYC as a potential therapeutic target for ovarian cancers expressing high levels of this oncoprotein. ©2015 American Association for Cancer Research.

  17. Patient selection and targeted treatment in the management of platinum-resistant ovarian cancer

    PubMed Central

    Leamon, Christopher P; Lovejoy, Chandra D; Nguyen, Binh

    2013-01-01

    Ovarian cancer (OC) has the highest mortality rate of any gynecologic cancer, and patients generally have a poor prognosis due to high chemotherapy resistance and late stage disease diagnosis. Platinum-resistant OC can be treated with cytotoxic chemotherapy such as paclitaxel, topotecan, pegylated liposomal doxorubicin, and gemcitabine, but many patients eventually relapse upon treatment. Fortunately, there are currently a number of targeted therapies in development for these patients who have shown promising results in recent clinical trials. These treatments often target the vascular endothelial growth factor pathway (eg, bevacizumab and aflibercept), DNA repair mechanisms (eg, iniparib and olaparib), or they are directed against folate related pathways (eg, pemetrexed, farletuzumab, and vintafolide). As many targeted therapies are only effective in a subset of patients, there is an increasing need for the identification of response predictive biomarkers. Selecting the right patients through biomarker screening will help tailor therapy to patients and decrease superfluous treatment to those who are biomarker negative; this approach should lead to improved clinical results and decreased toxicities. In this review the current targeted therapies used for treating platinum-resistant OC are discussed. Furthermore, use of prognostic and response predictive biomarkers to define OC patient populations that may benefit from specific targeted therapies is also highlighted. PMID:24109193

  18. Patient selection and targeted treatment in the management of platinum-resistant ovarian cancer.

    PubMed

    Leamon, Christopher P; Lovejoy, Chandra D; Nguyen, Binh

    2013-09-25

    Ovarian cancer (OC) has the highest mortality rate of any gynecologic cancer, and patients generally have a poor prognosis due to high chemotherapy resistance and late stage disease diagnosis. Platinum-resistant OC can be treated with cytotoxic chemotherapy such as paclitaxel, topotecan, pegylated liposomal doxorubicin, and gemcitabine, but many patients eventually relapse upon treatment. Fortunately, there are currently a number of targeted therapies in development for these patients who have shown promising results in recent clinical trials. These treatments often target the vascular endothelial growth factor pathway (eg, bevacizumab and aflibercept), DNA repair mechanisms (eg, iniparib and olaparib), or they are directed against folate related pathways (eg, pemetrexed, farletuzumab, and vintafolide). As many targeted therapies are only effective in a subset of patients, there is an increasing need for the identification of response predictive biomarkers. Selecting the right patients through biomarker screening will help tailor therapy to patients and decrease superfluous treatment to those who are biomarker negative; this approach should lead to improved clinical results and decreased toxicities. In this review the current targeted therapies used for treating platinum-resistant OC are discussed. Furthermore, use of prognostic and response predictive biomarkers to define OC patient populations that may benefit from specific targeted therapies is also highlighted.

  19. Cell membrane penetration and mitochondrial targeting by platinum-decorated ceria nanoparticles

    NASA Astrophysics Data System (ADS)

    Torrano, Adriano A.; Herrmann, Rudolf; Strobel, Claudia; Rennhak, Markus; Engelke, Hanna; Reller, Armin; Hilger, Ingrid; Wixforth, Achim; Bräuchle, Christoph

    2016-07-01

    In this work we investigate the interaction between endothelial cells and nanoparticles emitted by catalytic converters. Although catalyst-derived particles are recognized as growing burden added to environmental pollution, very little is known about their health impact. We use platinum-decorated ceria nanoparticles as model compounds for the actual emitted particles and focus on their fast uptake and association with mitochondria, the cell's powerhouse. Using live-cell imaging and electron microscopy we clearly show that 46 nm platinum-decorated ceria nanoparticles can rapidly penetrate cell membranes and reach the cytosol. Moreover, if suitably targeted, these particles are able to selectively attach to mitochondria. These results are complemented by cytotoxicity assays, thus providing insights into the biological effects of these particles on cells. Interestingly, no permanent membrane disruption or any other significant adverse effects on cells were observed. The unusual uptake behavior observed for 46 nm nanoparticles was not observed for equivalent but larger 143 nm and 285 nm platinum-decorated particles. Our results demonstrate a remarkable particle size effect in which particles smaller than ~50-100 nm escape the usual endocytic pathway and translocate directly into the cytosol, while particles larger than ~150 nm are internalized by conventional endocytosis. Since the small particles are able to bypass endocytosis they could be explored as drug and gene delivery vehicles. Platinum-decorated nanoparticles are therefore highly interesting in the fields of nanotoxicology and nanomedicine.In this work we investigate the interaction between endothelial cells and nanoparticles emitted by catalytic converters. Although catalyst-derived particles are recognized as growing burden added to environmental pollution, very little is known about their health impact. We use platinum-decorated ceria nanoparticles as model compounds for the actual emitted particles and

  20. Antibody fragment-conjugated polymeric micelles incorporating platinum drugs for targeted therapy of pancreatic cancer.

    PubMed

    Ahn, Jooyeon; Miura, Yutaka; Yamada, Naoki; Chida, Tsukasa; Liu, Xueying; Kim, Ahram; Sato, Ryuta; Tsumura, Ryo; Koga, Yoshikatsu; Yasunaga, Masahiro; Nishiyama, Nobuhiro; Matsumura, Yasuhiro; Cabral, Horacio; Kataoka, Kazunori

    2015-01-01

    Antibody-mediated therapies including antibody-drug conjugates (ADCs) have shown much potential in cancer treatment by tumor-targeted delivery of cytotoxic drugs. However, there is a limitation of payloads that can be delivered by ADCs. Integration of antibodies to drug-loaded nanocarriers broadens the applicability of antibodies to a wide range of therapeutics. Herein, we developed antibody fragment-installed polymeric micelles via maleimide-thiol conjugation for selectively delivering platinum drugs to pancreatic tumors. By tailoring the surface density of maleimide on the micelles, one tissue factor (TF)-targeting Fab' was conjugated to each carrier. Fab'-installed platinum-loaded micelles exhibited more than 15-fold increased cellular binding within 1 h and rapid cellular internalization compared to non-targeted micelles, leading to superior in vitro cytotoxicity. In vivo, Fab'-installed micelles significantly suppressed the growth of pancreatic tumor xenografts for more than 40 days, outperforming non-targeted micelles and free drugs. These results indicate the potential of Fab'-installed polymeric micelles for efficient drug delivery to solid tumors.

  1. Platinum(IV) Carboxylate Prodrug Complexes as Versatile Platforms for Targeted Chemotherapy.

    PubMed

    Ong, Jun Xiang; Yap, Siew Qi; Wong, Daniel Yuan Qiang; Chin, Chee Fei; Ang, Wee Han

    2015-01-01

    Kinetically-inert Pt(IV) carboxylate complexes have emerged in recent years as candidates for the development of next-generation platinum anticancer drugs. Being native prodrugs of clinically-important Pt(II) chemotherapeutic agents, the Pt(IV) scaffold can be exploited to incorporate additional functionalities while keeping the Pt(II) pharmacophore intact. This mini-review examines recent work performed to illuminate the mechanism of Pt(IV) prodrug activation and their use as versatile platforms for targeted chemotherapy.

  2. Targeted treatment of recurrent platinum-resistant ovarian cancer: current and emerging therapies

    PubMed Central

    Mantia-Smaldone, Gina M; Edwards, Robert P; Vlad, Anda M

    2010-01-01

    With advances in surgical techniques and chemotherapeutic agents, mortality rates from epithelial ovarian cancer (EOC) have slightly decreased over the last 30 years. However, EOC still ranks as the most deadly gynecologic cancer with an overall 5-year survival rate of 45%. Prognosis is especially disappointing for women with platinum-resistant disease, where 80% of patients will fail to respond to available therapies. Emerging treatment strategies have sub-sequently focused on targets which are integral to tumor growth and metastasis. In this review, we will focus on those innovative agents currently under investigation in clinical trials. PMID:21734812

  3. Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer.

    PubMed

    Chen, Ying; Camacho, Sandra Catalina; Silvers, Thomas R; Razak, Albiruni R A; Gabrail, Nashat Y; Gerecitano, John F; Kalir, Eva; Pereira, Elena; Evans, Brad R; Ramus, Susan J; Huang, Fei; Priedigkeit, Nolan; Rodriguez, Estefania; Donovan, Michael; Khan, Faisal; Kalir, Tamara; Sebra, Robert; Uzilov, Andrew; Chen, Rong; Sinha, Rileen; Halpert, Richard; Billaud, Jean-Noel; Shacham, Sharon; McCauley, Dilara; Landesman, Yosef; Rashal, Tami; Kauffman, Michael; Mirza, Mansoor R; Mau-Sørensen, Morten; Dottino, Peter; Martignetti, John A

    2017-03-15

    Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer.Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA). The effect of XPO1 inhibition, using the small-molecule inhibitors KPT-185 and KPT-330 (selinexor) alone or in combination with a platinum agent on cell viability, apoptosis, and the transcriptome was tested in immortalized and patient-derived ovarian cancer cell lines (PDCL) and platinum-resistant mice (PDX). Seven patients with late-stage, recurrent, and heavily pretreated ovarian cancer were treated with an oral XPO1 inhibitor.Results: XPO1 RNA overexpression and protein nuclear localization were correlated with decreased survival and platinum resistance in ovarian cancer. Targeted XPO1 inhibition decreased cell viability and synergistically restored platinum sensitivity in both immortalized ovarian cancer cells and PDCL. The XPO1 inhibitor-mediated apoptosis occurred through both p53-dependent and p53-independent signaling pathways. Selinexor treatment, alone and in combination with platinum, markedly decreased tumor growth and prolonged survival in platinum-resistant PDX and mice. In selinexor-treated patients, tumor growth was halted in 3 of 5 patients, including one with a partial response, and was safely tolerated by all.Conclusions: Taken together, these results provide evidence that XPO1 inhibition represents a new therapeutic strategy for overcoming platinum resistance in women with ovarian cancer. Clin Cancer Res; 23(6); 1552-63. ©2016 AACR. ©2016 American Association for Cancer Research.

  4. Stereochemical control of nucleosome targeting by platinum-intercalator antitumor agents

    PubMed Central

    Chua, Eugene Y.D.; Davey, Gabriela E.; Chin, Chee Fei; Dröge, Peter; Ang, Wee Han; Davey, Curt A.

    2015-01-01

    Platinum-based anticancer drugs act therapeutically by forming DNA adducts, but suffer from severe toxicity and resistance problems, which have not been overcome in spite of decades of research. And yet defined chromatin targets have generally not been considered in the drug development process. Here we designed novel platinum-intercalator species to target a highly deformed DNA site near the nucleosome center. Between two seemingly similar structural isomers, we find a striking difference in DNA site selectivity in vitro, which comes about from stereochemical constraints that limit the reactivity of the trans isomer to special DNA sequence elements while still allowing the cis isomer to efficiently form adducts at internal sites in the nucleosome core. This gives the potential for controlling nucleosome site targeting in vivo, which would engender sensitivity to epigenetic distinctions and in particular cell type/status-dependent differences in nucleosome positioning. Moreover, while both compounds yield very similar DNA-adduct structures and display antitumor cell activity rivalling that of cisplatin, the cis isomer, relative to the trans, has a much more rapid cytotoxic effect and distinct impact on cell function. The novel stereochemical principles for controlling DNA site selectivity we discovered could aid in the design of improved site discriminating agents. PMID:25916851

  5. Stereochemical control of nucleosome targeting by platinum-intercalator antitumor agents.

    PubMed

    Chua, Eugene Y D; Davey, Gabriela E; Chin, Chee Fei; Dröge, Peter; Ang, Wee Han; Davey, Curt A

    2015-06-23

    Platinum-based anticancer drugs act therapeutically by forming DNA adducts, but suffer from severe toxicity and resistance problems, which have not been overcome in spite of decades of research. And yet defined chromatin targets have generally not been considered in the drug development process. Here we designed novel platinum-intercalator species to target a highly deformed DNA site near the nucleosome center. Between two seemingly similar structural isomers, we find a striking difference in DNA site selectivity in vitro, which comes about from stereochemical constraints that limit the reactivity of the trans isomer to special DNA sequence elements while still allowing the cis isomer to efficiently form adducts at internal sites in the nucleosome core. This gives the potential for controlling nucleosome site targeting in vivo, which would engender sensitivity to epigenetic distinctions and in particular cell type/status-dependent differences in nucleosome positioning. Moreover, while both compounds yield very similar DNA-adduct structures and display antitumor cell activity rivalling that of cisplatin, the cis isomer, relative to the trans, has a much more rapid cytotoxic effect and distinct impact on cell function. The novel stereochemical principles for controlling DNA site selectivity we discovered could aid in the design of improved site discriminating agents. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates

    PubMed Central

    Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

    2017-01-01

    Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design. PMID:28467806

  7. Conjugated Platinum(IV)-Peptide Complexes for Targeting Angiogenic Tumor Vasculature

    PubMed Central

    Mukhopadhyay, Sumitra; Barnés, Carmen M.; Haskel, Ariel; Short, Sarah M.; Barnes, Katie R.; Lippard, Stephen J.

    2008-01-01

    The integrins αvβ3 and αvβ5 and the membrane-spanning surface protein aminopeptidase-N (APN) are highly expressed in tumor-induced angiogenesis, making them attractive targets for therapeutic intervention. Both integrins and APN recognize a broad range of peptides containing RGD (Arg-Gly-Asp) and NGR (Asn-Gly-Arg) motifs, respectively. Here, we describe the design, synthesis, and characterization of a series of mono- and difunctionalized platinum(IV) complexes in which a conjugated peptide motif, containing either RGD, CRGDC, (RGDfK)c or NGR, is appended as a ‘tumor-homing device’ to target tumor endothelial cells selectively over healthy cells. Platinum(IV)-peptide complexes with non-specific amino acids or peptide moieties were prepared as controls. Concentration-response curves of these compounds were evaluated against primary proliferating endothelial cells and tumor cell lines and compared to those of cisplatin, a well-described platinum-based chemotherapeutic agent. The Pt(IV)-RGD conjugates were highly and specifically cytotoxic to αvβ3 and αvβ5 containing cell lines, approaching the activity of cisplatin. The Pt(IV)-NGR complexes were less active than Pt(IV)-RGD-containing compounds but more active than non-specific Pt-peptide controls. Integrin αvβ3 mediated, at least in part, the anti-proliferative effect of an Pt(IV)-RGD conjugate, as demonstrated by a decreased inhibitory response when endothelial cells were either (1) incubated with an excess of αvβ3 /αvβ3-specific RGD pentapeptides, or (2) transfected with RNAi for β3, but not β1, integrins. These results suggest a rational approach to improved chemotherapy with Pt(IV)-peptide conjugates by selective drug delivery to the tumor compartment. PMID:17845003

  8. Conjugated platinum(IV)-peptide complexes for targeting angiogenic tumor vasculature.

    PubMed

    Mukhopadhyay, Sumitra; Barnés, Carmen M; Haskel, Ariel; Short, Sarah M; Barnes, Katie R; Lippard, Stephen J

    2008-01-01

    The integrins alpha vbeta3 and alpha vbeta5 and the membrane-spanning surface protein aminopeptidase N (APN) are highly expressed in tumor-induced angiogenesis, making them attractive targets for therapeutic intervention. Both integrins and APN recognize a broad range of peptides containing RGD (Arg-Gly-Asp) and NGR (Asn-Gly-Arg) motifs, respectively. Here, we describe the design, synthesis, and characterization of a series of mono- and difunctionalized platinum(IV) complexes in which a conjugated peptide motif, containing RGD, (CRGDC)c, (RGDfK)c, or NGR, is appended as a "tumor-homing device" to target tumor endothelial cells selectively over healthy cells. Platinum(IV)-peptide complexes with nonspecific amino acids or peptide moieties were prepared as controls. Concentration-response curves of these compounds were evaluated against primary proliferating endothelial cells and tumor cell lines and compared to those of cisplatin, a well-described platinum-based chemotherapeutic agent. The Pt(IV)-RGD conjugates were highly and specifically cytotoxic to cell lines containing alpha vbeta3 and alpha vbeta5, approaching the activity of cisplatin. The Pt(IV)-NGR complexes were less active than Pt(IV)-RGD-containing compounds but more active than nonspecific Pt-peptide controls. Integrin alpha vbeta3 mediated, at least in part, the anti-proliferative effect of a Pt(IV)-RGD conjugate, as demonstrated by a decreased inhibitory response when endothelial cells were either (1) incubated with an excess of alpha vbeta3/alpha vbeta5-specific RGD pentapeptides or (2) transfected with RNAi for beta 3, but not beta 1, integrins. These results suggest a rational approach to improved chemotherapy with Pt(IV)-peptide conjugates by selective drug delivery to the tumor compartment.

  9. GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

    PubMed

    Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

    2017-06-13

    Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

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

    PubMed

    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.

  11. Neuropilin-1-targeted gold nanoparticles enhance therapeutic efficacy of platinum(IV) drug for prostate cancer treatment.

    PubMed

    Kumar, Anil; Huo, Shuaidong; Zhang, Xu; Liu, Juan; Tan, Aaron; Li, Shengliang; Jin, Shubin; Xue, Xiangdong; Zhao, YuanYuan; Ji, Tianjiao; Han, Lu; Liu, Hong; Zhang, XiaoNing; Zhang, Jinchao; Zou, Guozhang; Wang, Tianyou; Tang, Suoqin; Liang, Xing-Jie

    2014-05-27

    Platinum-based anticancer drugs such as cisplatin, oxaliplatin, and carboplatin are some of the most potent chemotherapeutic agents but have limited applications due to severe dose-limiting side effects and a tendency for cancer cells to rapidly develop resistance. The therapeutic index can be improved through use of nanocarrier systems to target cancer cells efficiently. We developed a unique strategy to deliver a platinum(IV) drug to prostate cancer cells by constructing glutathione-stabilized (Au@GSH) gold nanoparticles. Glutathione (GSH) has well-known antioxidant properties, which lead to cancer regression. Here, we exploit the advantages of both the antioxidant properties and high surface-area-to-volume ratio of Au@GSH NPs to demonstrate their potential for delivery of a platinum(IV) drug by targeting the neuropilin-1 receptor (Nrp-1). A lethal dose of a platinum(IV) drug functionalized with the Nrp-1-targeting peptide (CRGDK) was delivered specifically to prostate cancer cells in vitro. Targeted peptide ensures specific binding to the Nrp-1 receptor, leading to enhanced cellular uptake level and cell toxicity. The nanocarriers were themselves nontoxic, but exhibited high cytotoxicity and increased efficacy when functionalized with the targeting peptide and drug. The uptake of drug-loaded nanocarriers is dependent on the interaction with Nrp-1 in cell lines expressing high (PC-3) and low (DU-145) levels of Nrp-1, as confirmed through inductively coupled plasma mass spectrometry and confocal microscopy. The nanocarriers have effective anticancer activity, through upregulation of nuclear factor kappa-B (NF-κB) protein (p50 and p65) expression and activation of NF-κB-DNA-binding activity. Our preliminary investigations with platinum(IV)-functionalized gold nanoparticles along with a targeting peptide hold significant promise for future cancer treatment.

  12. Linker design for the modular assembly of multifunctional and targeted platinum(ii)-containing anticancer agents.

    PubMed

    Ding, S; Bierbach, U

    2016-08-16

    A versatile and efficient modular synthetic platform was developed for assembling multifunctional conjugates and targeted forms of platinum-(benz)acridines, a class of highly cytotoxic DNA-targeted hybrid agents. The synthetic strategy involved amide coupling between succinyl ester-modified platinum compounds (P1, P2) and a set of 11 biologically relevant primary and secondary amines (N1-N11). To demonstrate the feasibility and versatility of the approach, a structurally and functionally diverse range of amines was introduced. These include biologically active molecules, such as rucaparib (a PARP inhibitor), E/Z-endoxifen (an estrogen receptor antagonist), and a quinazoline-based tyrosine kinase inhibitor. Micro-scale reactions in Eppendorf tubes or on 96-well plates were used to screen for optimal coupling conditions in DMF solution with carbodiimide-, uronium-, and phosphonium-based compounds, as well as other common coupling reagents. Reactions with the phosphonium-based coupling reagent PyBOP produced the highest yields and gave the cleanest conversions. Furthermore, it was demonstrated that the chemistry can also be performed in aqueous media and is amenable to parallel synthesis based on multiple consecutive reactions in DMF in a "one-tube" format. In-line LC-MS was used to assess the stability of the conjugates in physiologically relevant buffers. Hydrolysis of the conjugates occurs at the ester moiety and is facilitated by the aquated metal moiety under low-chloride ion conditions. The rate of ester cleavage greatly depends on the nature of the amine component. Potential applications of the linker technology are discussed.

  13. Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells.

    PubMed

    Setzler, Brian P; Zhuang, Zhongbin; Wittkopf, Jarrid A; Yan, Yushan

    2016-12-06

    Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW(-1) in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

  14. Activity targets for nanostructured platinum-group-metal-free catalysts in hydroxide exchange membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Setzler, Brian P.; Zhuang, Zhongbin; Wittkopf, Jarrid A.; Yan, Yushan

    2016-12-01

    Fuel cells are the zero-emission automotive power source that best preserves the advantages of gasoline automobiles: low upfront cost, long driving range and fast refuelling. To make fuel-cell cars a reality, the US Department of Energy has set a fuel cell system cost target of US$30 kW-1 in the long-term, which equates to US$2,400 per vehicle, excluding several major powertrain components (in comparison, a basic, but complete, internal combustion engine system costs approximately US$3,000). To date, most research for automotive applications has focused on proton exchange membrane fuel cells (PEMFCs), because these systems have demonstrated the highest power density. Recently, however, an alternative technology, hydroxide exchange membrane fuel cells (HEMFCs), has gained significant attention, because of the possibility to use stable platinum-group-metal-free catalysts, with inherent, long-term cost advantages. In this Perspective, we discuss the cost profile of PEMFCs and the advantages offered by HEMFCs. In particular, we discuss catalyst development needs for HEMFCs and set catalyst activity targets to achieve performance parity with state-of-the-art automotive PEMFCs. Meeting these targets requires careful optimization of nanostructures to pack high surface areas into a small volume, while maintaining high area-specific activity and favourable pore-transport properties.

  15. Investigating the cellular fate of a DNA-targeted platinum-based anticancer agent by orthogonal double-click chemistry.

    PubMed

    Qiao, Xin; Ding, Song; Liu, Fang; Kucera, Gregory L; Bierbach, Ulrich

    2014-03-01

    Confocal fluorescence microscopy was used to study a platinum-based anticancer agent in intact NCI-H460 lung cancer cells. Orthogonal copper-catalyzed azide-alkyne cycloaddition (click) reactions were used to simultaneously determine the cell-cycle-specific localization of the azide-functionalized platinum-acridine agent 1 and monitor its effects on nucleic acid metabolism. Copper-catalyzed postlabeling showed advantages over copper-free click chemistry using a dibenzocyclooctyne (DIBO)-modified reporter dye, which produced high background levels in microscopic images and failed to efficiently label platinum adducts in chromatin. Compound 1 was successfully labeled with the fluorophore DIBO to yield 1* (characterized by in-line high-performance liquid chromatography/electrospray mass spectrometry). 1 and 1* show a high degree of colocalization in the confocal images, but the ability of 1* to target the (compacted) chromatin was markedly reduced, most likely owing to the steric bulk introduced by the DIBO tag. Nuclear platinum levels correlated inversely with the ability of the cells to synthesize DNA and cause cell cycle arrest, as confirmed by bivariate flow cytometry analysis. In addition, a decrease in the level of cellular transcription, shrinkage of the nucleolar regions, and redistribution of RNA into the cytosol were observed. Postlabeling in conjunction with colocalization experiments is a useful tool for studying the cell killing mechanism of this type of DNA-targeted agent.

  16. Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer.

    PubMed

    Pchejetski, Dmitri; Alfraidi, Albandri; Sacco, Keith; Alshaker, Heba; Muhammad, Aun; Monzon, Leonardo

    2016-08-01

    In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the non-specific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies.

  17. Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study.

    PubMed

    Moore, Kathleen N; Martin, Lainie P; O'Malley, David M; Matulonis, Ursula A; Konner, Jason A; Perez, Raymond P; Bauer, Todd M; Ruiz-Soto, Rodrigo; Birrer, Michael J

    2017-04-01

    Purpose This phase I expansion cohort study evaluated the safety and clinical activity of mirvetuximab soravtansine (IMGN853), an antibody-drug conjugate consisting of a humanized anti-folate receptor alpha (FRα) monoclonal antibody linked to the tubulin-disrupting maytansinoid DM4, in a population of patients with FRα-positive and platinum-resistant ovarian cancer. Patients and Methods Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer received IMGN853 at 6.0 mg/kg (adjusted ideal body weight) once every 3 weeks. Eligibility included a minimum requirement of FRα positivity by immunohistochemistry (≥ 25% of tumor cells with at least 2+ staining intensity). Adverse events, tumor response (via Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), and progression-free survival (PFS) were determined. Results Forty-six patients were enrolled. Adverse events were generally mild (≤ grade 2), with diarrhea (44%), blurred vision (41%), nausea (37%), and fatigue (30%) being the most commonly observed treatment-related toxicities. Grade 3 fatigue and hypotension were reported in two patients each (4%). For all evaluable patients, the confirmed objective response rate was 26%, including one complete and 11 partial responses, and the median PFS was 4.8 months. The median duration of response was 19.1 weeks. Notably, in the subset of patients who had received three or fewer prior lines of therapy (n = 23), an objective response rate of 39%, PFS of 6.7 months, and duration of response of 19.6 weeks were observed. Conclusion IMGN853 exhibited a manageable safety profile and was active in platinum-resistant ovarian cancer, with the strongest signals of efficacy observed in less heavily pretreated individuals. On the basis of these findings, the dose, schedule, and target population were identified for a phase III trial of IMGN853 monotherapy in patients with platinum-resistant disease.

  18. A Photoactivatable Platinum(IV) Complex Targeting Genomic DNA and Histone Deacetylases.

    PubMed

    Kasparkova, Jana; Kostrhunova, Hana; Novakova, Olga; Křikavová, Radka; Vančo, Ján; Trávníček, Zdeněk; Brabec, Viktor

    2015-11-23

    We report toxic effects of a photoactivatable platinum(IV) complex conjugated with suberoyl-bis-hydroxamic acid in tumor cells. The conjugate exerts, after photoactivation, two functions: activity as both a platinum(II) anticancer drug and histone deacetylase (HDAC) inhibitor in cancer cells. This approach relies on the use of a Pt(IV) pro-drug, acting by two independent mechanisms of biological action in a cooperative manner, which can be selectively photoactivated to a cytotoxic species in and around a tumor, thereby increasing selectivity towards cancer cells. These results suggest that this strategy is a valuable route to design new platinum agents with higher efficacy for photodynamic anticancer chemotherapy.

  19. A targeted theranostic platinum(IV) prodrug containing a luminogen with aggregation-induced emission (AIE) characteristics for in situ monitoring of drug activation.

    PubMed

    Yuan, Youyong; Chen, Yilong; Tang, Ben Zhong; Liu, Bin

    2014-04-14

    A targeted theranostic platinum(IV) prodrug based on a luminogen with aggregation-induced emission (AIE) characteristics was developed for selective and real-time monitoring of drug activation in situ.

  20. Targeting drug transport mechanisms for improving platinum-based cancer chemotherapy

    PubMed Central

    Chen, Helen HW; Chen, Wen-Chung; Liang, Zhang-Dong; Tsai, Wen-Bin; Long, Yan; Aiba, Isamu; Fu, Siqing; Broaddus, Russell; Liu, Jinsong; Feun, Lynn G; Savaraj, Niramol; Kuo, Macus Tien

    2016-01-01

    Introduction Platinum (Pt)-based antitumor agents remain important chemotherapeutic agents for treating many human malignancies. Elevated expression of the human high-affinity copper transporter 1 (hCtr1), resulting in enhanced Pt drug transport into cells, has been shown to be associated with improved treatment efficacy. Thus, targeting hCtr1 upregulation is an attractive strategy for improving the treatment efficacy of Pt-based cancer chemotherapy. Area covered Regulation of hCtr1 expression by cellular copper homeostasis is discussed. Association of elevated hCtr1 expression with intrinsic sensitivity of ovarian cancer to Pt drugs is presented. Mechanism of copper-lowering agents in enhancing hCtr1-mediated cis-diamminedichloroplatinum (II) (cisplatin, cDDP) transport is reviewed. Applications of copper chelation strategy in overcoming cDDP resistance through enhanced hCtr1 expression are evaluated. Expert opinion While both transcriptional and posttranslational mechanisms of hCtr1 regulation by cellular copper bioavailability have been proposed, detailed molecular insights into hCtr1 regulation by copper homeostasis remain needed. Recent clinical study using a copper-lowering agent in enhancing hCtr1-mediated drug transport has achieved incremental improvement in overcoming Pt drug resistance. Further improvements in identifying predictive measures in the subpopulation of patients that can benefit from the treatment are needed. PMID:26004625

  1. Evaluation of platinum chemotherapy in combination with HER2-targeted α-particle radiation.

    PubMed

    Milenic, Diane E; Baidoo, Kwamena E; Shih, Joanna H; Wong, Karen J; Brechbiel, Martin W

    2013-01-01

    The studies described herein assess the potential of combining platinum-based chemotherapy with high-linear energy transfer (LET) α-particle-targeted radiation therapy using trastuzumab as the delivery vehicle. An initial study explored the combination of cisplatin with (213)Bi-trastuzumab in the LS-174T i.p. xenograft model. This initial study determined the administration sequence of cisplatin and (213)Bi-trastuzumab. Cisplatin coinjected with (213)Bi-trastuzumab increased the median survival (MS) to 90 days versus 65 days for (213)Bi-trastuzumab alone. Toxicity was observed with a weight loss of 17.6% in some of the combined treatment groups. Carboplatin proved to be better tolerated. Maximal therapeutic benefit, that is, a 5.1-fold increase in MS, was obtained in the group injected with (213)Bi-trastuzumab, followed by carboplatin 24 hours later. This was further improved by administration of multiple weekly doses of carboplatin. The MS achieved with administration of 3 doses of carboplatin was 180 days versus 60 days with (213)Bi-trastuzumab alone. The combination of carboplatin with (212)Pb radioimmunotherapy was also evaluated. The therapeutic efficacy of (212)Pb-trastuzumab (58-day MS) increased when the mice were pretreated with carboplatin 24 hours prior (157-day MS). These results again demonstrate the necessity of empirically determining the administration sequence when combining therapeutic modalities.

  2. Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells.

    PubMed

    Yu, Seong-Lan; Lee, Dong Chul; Sohn, Hyun Ahm; Lee, Soo Young; Jeon, Hyo Sung; Lee, Joon H; Park, Chang Gyo; Lee, Hoi Young; Yeom, Young Il; Son, Ji Woong; Yoon, Yoo Sang; Kang, Jaeku

    2016-12-01

    MicroRNAs (miRNAs) are recognized as crucial posttranscriptional regulators of gene expression, and play critical roles as oncogenes or tumor suppressors in various cancers. Here, we show that miR-196b is upregulated in mesenchymal-like-state non-small cell lung cancer (NSCLC) cells and lung cancer tissues. Moreover, miR-196b upregulation stimulates cell invasion and a change in cell morphology to a spindle shape via loss of cell-to-cell contacts. We identified homeobox A9 (HOXA9) as a target gene of miR-196b by using public databases such as TargetScan, miRDB, and microRNA.org. HOXA9 expression is inversely correlated with miR-196b levels in clinical NSCLC samples as compared to that in corresponding control samples, and with the migration and invasion of NSCLC cells. Ectopic expression of HOXA9 resulted in a suppression of miR-196b-induced cell invasion, and HOXA9 reexpression increased E-cadherin expression. Furthermore, HOXA9 potently attenuated the expression of snail family zinc finger 2 (SNAI2/SLUG) and matrix metallopeptidase 9 (MMP9) by controlling the binding of nuclear factor-kappa B to the promoter of SLUG and MMP9 genes, respectively. Therefore, we suggest that HOXA9 plays a central role in controlling the aggressive behavior of lung cancer cells and that miR-196b can serve as a potential target for developing anticancer agents. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  3. Investigating the cellular fate of a DNA-targeted platinum-based anticancer agent by orthogonal double-click chemistry

    PubMed Central

    Qiao, Xin; Ding, Song; Liu, Fang; Kucera, Gregory L.

    2014-01-01

    Confocal fluorescence microscopy was used to study a platinum-based anticancer agent in intact NCI-H460 lung cancer cells. Orthogonal copper-catalyzed azide–alkyne cycloaddition (click) reactions were used to simultaneously determine the cell-cycle-specific localization of the azide-functionalized platinum–acridine agent 1 and monitor its effects on nucleic acid metabolism. Copper-catalyzed postlabeling showed advantages over copper-free click chemistry using a dibenzocyclooctyne (DIBO)-modified reporter dye, which produced high background levels in microscopic images and failed to efficiently label platinum adducts in chromatin. Compound 1 was successfully labeled with the fluorophore DIBO to yield 1* (characterized by in-line high-performance liquid chromatography/electrospray mass spectrometry). 1 and 1* show a high degree of colocalization in the confocal images, but the ability of 1* to target the (compacted) chromatin was markedly reduced, most likely owing to the steric bulk introduced by the DIBO tag. Nuclear platinum levels correlated inversely with the ability of the cells to synthesize DNA and cause cell cycle arrest, as confirmed by bivariate flow cytometry analysis. In addition, a decrease in the level of cellular transcription, shrinkage of the nucleolar regions, and redistribution of RNA into the cytosol were observed. Postlabeling in conjunction with colocalization experiments is a useful tool for studying the cell killing mechanism of this type of DNA-targeted agent. PMID:24407462

  4. Anticancer Platinum(IV) Prodrugs Containing Monoaminophosphonate Ester as a Targeting Group Inhibit Matrix Metalloproteinases and Reverse Multidrug Resistance.

    PubMed

    Huang, Xiaochao; Huang, Rizhen; Gou, Shaohua; Wang, Zhimei; Wang, Hengshan

    2017-04-19

    A novel class of platinum(IV) complexes comprising a monoaminophosphonate ester moiety, which can not only act as a bone-targeting group but also inhibit matrix metalloproteinases (MMPs), were designed and synthesized. Biological assay of these compounds showed that they had potent antitumor activities against the tested cancer cell lines compared with cisplatin and oxaliplatin and indicated low cytotoxicity to human normal liver cells. Particularly, the platinum(IV) complexes were very sensitive to cisplatin resistant cancer cell lines. The corresponding structure-activity relationships were studied and discussed. Related mechanism study revealed that the typical complex 11 caused cell cycle arrest at S phase and induced apoptosis in Bel-7404 cells via a mitochondrial-dependent apoptosis pathway. Moreover, complex 11 had potent ability to inhibit the tumor growth in the NCI-H460 xenograft model comparable to cisplatin.

  5. Active targeting of cancer cells using folic acid-conjugated platinum nanoparticles

    NASA Astrophysics Data System (ADS)

    Teow, Yiwei; Valiyaveettil, Suresh

    2010-12-01

    Interaction of nanoparticles with human cells is an interesting topic for understanding toxicity and developing potential drug candidates. Water soluble platinum nanoparticles were synthesized viareduction of hexachloroplatinic acid using sodium borohydride in the presence of capping agents. The bioactivity of folic acid and poly(vinyl pyrrolidone) capped platinum nanoparticles (Pt-nps) has been investigated using commercially available cell lines. In the cell viability experiments, PVP-capped nanoparticles were found to be less toxic (>80% viability), whereas, folic acid-capped platinum nanoparticles showed a reduced viability down to 24% after 72 h of exposure at a concentration of 100 μg ml-1 for MCF7 breast cancer cells. Such toxicity, combined with the possibility to incorporate functional organic molecules as capping agents, can be used for developing new drug candidates.

  6. Synthesis, biological activity, and DNA-damage profile of platinum-threading intercalator conjugates designed to target adenine.

    PubMed

    Guddneppanavar, Rajsekhar; Saluta, Gilda; Kucera, Gregory L; Bierbach, Ulrich

    2006-06-01

    PT-ACRAMTU {[PtCl(en)(ACRAMTU)](NO3)2, 2; ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea, 1, en = ethane-1,2-diamine} is the prototype of a series of DNA-targeted adenine-affinic dual intercalating/platinating agents. Several novel 4,9-disubstituted acridines and the corresponding platinum-acridine conjugates were synthesized. The newly introduced 4-carboxamide side chains contain H-bond donor/acceptor functions designed to promote groove- and sequence-specific platinum binding. In HL-60 (leukemia) and H460 (lung) cancer cells, IC50 values in the micromolar to millimolar range were observed. Several of the intercalators show enhanced cytotoxicity compared to prototype 1, but conjugate 2 appears to be the most potent hybrid agent. Enzymatic digestion assays in conjunction with liquid chromatography-electrospray mass spectrometry analysis indicate that the new conjugates produce PT-ACRAMTU-type DNA damage. Platinum-modified 2'-deoxyguanosine, dG, and several dinucleotide fragments, d(NpN)*, were detected. One of the conjugates showed significantly higher levels of binding to A-containing sites than conjugate 2 (35 +/- 3% vs 24 +/- 3%). Possible structure-activity relationships are discussed.

  7. Endoglin (CD105) contributes to platinum resistance and is a target for tumor-specific therapy in epithelial ovarian cancer

    PubMed Central

    Ziebarth, Angela J.; Nowsheen, Somaira; Steg, Adam D.; Shah, Monjri M.; Katre, Ashwini A.; Dobbin, Zachary C.; Han, Hee-Dong; Lopez-Berestein, Gabriel; Sood, Anil K.; Conner, Michael; Yang, Eddy S.; Landen, Charles N.

    2012-01-01

    Purpose Endoglin (ENG, CD105) is a membranous protein overexpressed in tumor-associated endothelial cells, chemoresistant populations of ovarian cancer cells, and potentially stem cells. Our objective was to evaluate the effects and mechanisms of targeting endoglin in ovarian cancer. Experimental Design Global and membranous endoglin expression was evaluated in multiple ovarian cancer lines. In vitro, the effects of siRNA-mediated endoglin knockdown with and without chemotherapy were evaluated by MTT assay, cell-cycle analysis, alkaline comet assay, γ-H2AX foci formation, and qPCR. In an orthotopic mouse model, endoglin was targeted with chitosan-encapsulated siRNA with and without carboplatin. Results Endoglin expression was surprisingly predominantly cytoplasmic, with a small population of surface-positive cells. Endoglin inhibition decreased cell viability, increased apoptosis, induced double-stranded DNA damage, and increased cisplatin sensitivity. Targeting endoglin downregulates expression of numerous DNA repair genes, including BARD1, H2AFX, NBN, NTHL1, and SIRT1. BARD1 was also associated with platinum resistance, and was induced by platinum exposure. In vivo, anti-endoglin treatment decreased tumor weight in both ES2 and HeyA8MDR models when compared to control (35-41% reduction, p<0.05). Endoglin inhibition with carboplatin was associated with even greater inhibitory effect when compared to control (58-62% reduction, p<0.001). Conclusions Endoglin downregulation promotes apoptosis, induces significant DNA damage through modulation of numerous DNA repair genes, and improves platinum sensitivity both in vivo and in vitro. Anti-endoglin therapy would allow dual treatment of both tumor angiogenesis and a subset of aggressive tumor cells expressing endoglin and is being actively pursued as therapy in ovarian cancer. PMID:23147994

  8. Gemcitabine as a molecular targeting agent that blocks the Akt cascade in platinum-resistant ovarian cancer

    PubMed Central

    2014-01-01

    -abdominal dissemination and production of ascites in the athymic nude mice inoculated with Caov-3 cells. Conclusions We herein demonstrated that Gemcitabine inhibits the Akt kinase activity and angiogenetic activity following treatment with Cisplatin in platinum-resistant ovarian cancer cells. These results provide a rationale for using Gemcitabine in clinical regimens containing molecular targeting agents against platinum-resistant ovarian cancers. PMID:24713296

  9. Gemcitabine as a molecular targeting agent that blocks the Akt cascade in platinum-resistant ovarian cancer.

    PubMed

    Kawaguchi, Hiroshi; Terai, Yoshito; Tanabe, Akiko; Sasaki, Hiroshi; Takai, Masaaki; Fujiwara, Satoe; Ashihara, Keisuke; Tanaka, Yoshimichi; Tanaka, Tomohito; Tsunetoh, Satoshi; Kanemura, Masanori; Ohmichi, Masahide

    2014-04-09

    ascites in the athymic nude mice inoculated with Caov-3 cells. We herein demonstrated that Gemcitabine inhibits the Akt kinase activity and angiogenetic activity following treatment with Cisplatin in platinum-resistant ovarian cancer cells. These results provide a rationale for using Gemcitabine in clinical regimens containing molecular targeting agents against platinum-resistant ovarian cancers.

  10. Multi-platinum anti-cancer agents. Substitution-inert compounds for tumor selectivity and new targets.

    PubMed

    Farrell, N P

    2015-12-21

    This tutorial review summarizes chemical, biophysical and cellular biological properties of formally substitution-inert "non-covalent" polynuclear platinum complexes (PPCs). We demonstrate how modulation of the pharmacological factors affecting platinum compound cytotoxicity such as cellular accumulation, reactivity toward extracellular and intracellular sulfur-ligand nucleophiles and consequences of DNA binding is achieved to afford a profile of biological activity distinct from that of covalently-binding agents. The DNA binding of substitution-inert complexes is achieved by molecular recognition through minor groove spanning and backbone tracking of the phosphate clamp. In this situation, the square-planar tetra-am(m)ine Pt(ii) coordination units hydrogen bond to phosphate oxygen OP atoms to form bidentate N-O-N motifs. The modular nature of the polynuclear compounds results in high-affinity binding to DNA and very efficient nuclear condensation. These combined effects distinguish the phosphate clamp as a third mode of ligand-DNA binding, discrete from intercalation and minor-groove binding. The cellular consequences mirror those of the biophysical studies and a significant portion of nuclear DNA is compacted, a unique effect different from mitosis, senescence or apoptosis. Substitution-inert PPCs display cytotoxicity similar to cisplatin in a wide range of cell lines, and sensitivity is indifferent to p53 status. Cellular accumulation is mediated through binding to heparan sulfate proteoglycans (HSPG) allowing for possibilities of tumor selectivity as well as disruption of HSPG function, opening new targets for platinum antitumor agents. The combined properties show that covalently-binding chemotypes are not the unique arbiters of cytotoxicity and antitumor activity and meaningful antitumor profiles can be achieved even in the absence of Pt-DNA bond formation. These dual properties make the substitution-inert compounds a unique class of inherently dual

  11. Novel platinum(IV) complexes conjugated with a wogonin derivative as multi-targeted anticancer agents.

    PubMed

    Qin, Xiaodong; Xu, Gang; Chen, Feihong; Fang, Lei; Gou, Shaohua

    2017-04-15

    Platinum-based complexes like cisplatin and oxaliplatin are well known the mainstay of chemotherapy regimens on clinic. Wogonin, a natural product that possesses wide biological activities, is now in phase I clinical test as an anticancer agent in China. Herein reported are a series of novel Pt(IV) complexes that conjugated a wogonin derivative (compound 3) to the axial position via a linker group. After being tethered to the platinum(IV) complexes, the wogonin derivative provided multiple anticancer effects, especially in compound 10, a fusion containing wogonin and cisplatin units. Compound 10 not only inherited the genotoxicity from cisplatin, but also obtained the COX inhibitory property from the wogonin derivative. Further mechanistic investigation revealed that compound 10 caused the accumulation of ROS, decreased the mitochondrial membrane potential (ΔΨm) and then activated the p53 pathway. Overall, the research demonstrates that the "integrative" prodrug can be an effective strategy to promote the anticancer potency of Pt-based drugs for cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    PubMed Central

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-01-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted. PMID:27150583

  13. A platinum-based hybrid drug design approach to circumvent acquired resistance to molecular targeted tyrosine kinase inhibitors

    NASA Astrophysics Data System (ADS)

    Wei, Yuming; Poon, Daniel C.; Fei, Rong; Lam, Amy S. M.; Au-Yeung, Steve C. F.; To, Kenneth K. W.

    2016-05-01

    Three molecular targeted tyrosine kinase inhibitors (TKI) were conjugated to classical platinum-based drugs with an aim to circumvent TKI resistance, predominately mediated by the emergence of secondary mutations on oncogenic kinases. The hybrids were found to maintain specificity towards the same oncogenic kinases as the original TKI. Importantly, they are remarkably less affected by TKI resistance, presumably due to their unique structure and the observed dual mechanism of anticancer activity (kinase inhibition and DNA damage). The study is also the first to report the application of a hybrid drug approach to switch TKIs from being efflux transporter substrates into non-substrates. TKIs cannot penetrate into the brain for treating metastases because of efflux transporters at the blood brain barrier. The hybrids were found to escape drug efflux and they accumulate more than the original TKI in the brain in BALB/c mice. Further development of the hybrid compounds is warranted.

  14. The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs

    PubMed Central

    Johnstone, Timothy C.; Suntharalingam, Kogularamanan; Lippard, Stephen J.

    2016-01-01

    The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer,, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing non-classical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore non-classical platinum(II) complexes with trans geometry and with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-treat agents, and photoactivatable platinum(IV) complexes. Nanodelivery particles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also reflect our optimism that the next generation of platinum cancer drugs is about to arrive. PMID:26865551

  15. The Next Generation of Platinum Drugs: Targeted Pt(II) Agents, Nanoparticle Delivery, and Pt(IV) Prodrugs.

    PubMed

    Johnstone, Timothy C; Suntharalingam, Kogularamanan; Lippard, Stephen J

    2016-03-09

    The platinum drugs, cisplatin, carboplatin, and oxaliplatin, prevail in the treatment of cancer, but new platinum agents have been very slow to enter the clinic. Recently, however, there has been a surge of activity, based on a great deal of mechanistic information, aimed at developing nonclassical platinum complexes that operate via mechanisms of action distinct from those of the approved drugs. The use of nanodelivery devices has also grown, and many different strategies have been explored to incorporate platinum warheads into nanomedicine constructs. In this Review, we discuss these efforts to create the next generation of platinum anticancer drugs. The introduction provides the reader with a brief overview of the use, development, and mechanism of action of the approved platinum drugs to provide the context in which more recent research has flourished. We then describe approaches that explore nonclassical platinum(II) complexes with trans geometry or with a monofunctional coordination mode, polynuclear platinum(II) compounds, platinum(IV) prodrugs, dual-threat agents, and photoactivatable platinum(IV) complexes. Nanoparticles designed to deliver platinum(IV) complexes will also be discussed, including carbon nanotubes, carbon nanoparticles, gold nanoparticles, quantum dots, upconversion nanoparticles, and polymeric micelles. Additional nanoformulations, including supramolecular self-assembled structures, proteins, peptides, metal-organic frameworks, and coordination polymers, will then be described. Finally, the significant clinical progress made by nanoparticle formulations of platinum(II) agents will be reviewed. We anticipate that such a synthesis of disparate research efforts will not only help to generate new drug development ideas and strategies, but also will reflect our optimism that the next generation of approved platinum cancer drugs is about to arrive.

  16. Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide

    PubMed Central

    Serpe, Loredana; Gallicchio, Margherita; Canaparo, Roberto; Dosio, Franco

    2014-01-01

    Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin) comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent “tumor-associated antigen”. With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide) for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide) as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy. PMID:24516337

  17. Targeted treatment of folate receptor-positive platinum-resistant ovarian cancer and companion diagnostics, with specific focus on vintafolide and etarfolatide.

    PubMed

    Serpe, Loredana; Gallicchio, Margherita; Canaparo, Roberto; Dosio, Franco

    2014-01-01

    Among the gynecological malignancies, ovarian cancer is the leading cause of mortality in developed countries. Treatment of ovarian cancer is based on surgery integrated with chemotherapy. Platinum-based drugs (cisplatin and carboplatin) comprise the core of first-line chemotherapy for patients with advanced ovarian cancer. Platinum-resistant ovarian cancer can be treated with cytotoxic chemotherapeutics such as paclitaxel, topotecan, PEGylated liposomal doxorubicin, or gemcitabine, but many patients eventually relapse on treatment. Targeted therapies based on agents specifically directed to overexpressed receptors, or to selected molecular targets, may be the future of clinical treatment. In this regard, overexpression of folate receptor-α on the surface of almost all epithelial ovarian cancers makes this receptor an excellent "tumor-associated antigen". With appropriate use of spacers/linkers, folate-targeted drugs can be distributed within the body, where they preferentially bind to ovarian cancer cells and are released inside their target cells. Here they can exert their desired cytotoxic function. Based on this strategy, 12 years after it was first described, a folate-targeted vinblastine derivative has now reached Phase III clinical trials in ovarian cancer. This review examines the importance of folate targeting, the state of the art of a vinblastine folate-targeted agent (vintafolide) for treating platinum-resistant ovarian cancer, and its diagnostic companion (etarfolatide) as a prognostic agent. Etarfolatide is a valuable noninvasive diagnostic imaging agent with which to select ovarian cancer patient populations that may benefit from this specific targeted therapy.

  18. Highly efficient colorimetric detection of target cancer cells utilizing superior catalytic activity of graphene oxide-magnetic-platinum nanohybrids

    NASA Astrophysics Data System (ADS)

    Kim, Moon Il; Kim, Min Su; Woo, Min-Ah; Ye, Youngjin; Kang, Kyoung Suk; Lee, Jinwoo; Park, Hyun Gyu

    2014-01-01

    Enzyme-linked immunosorbent assays (ELISAs) have most widely been applied in immunoassays for several decades. However, several unavoidable limitations (e.g., instability caused by structural unfolding) of natural enzymes have hindered their widespread applications. Here, we describe a new nanohybrid consisting of Fe3O4 magnetic nanoparticles (MNPs) and platinum nanoparticles (Pt NPs), simultaneously immobilized on the surface of graphene oxide (GO). By synergistically integrating highly catalytically active Pt NPs and MNPs on GO whose frameworks possess high substrate affinity, the nanohybrid is able to achieve up to a 30-fold higher maximal reaction velocity (Vmax) compared to that of free GO for the colorimetric reaction of the peroxidase substrate, 3,3',5,5'-tetramethylbenzidine (TMB), and enable rapid detection of target cancer cells. Specifically, using this new assay system, clinically important breast cancer cells are detected in a 5 min time period at room temperature with high specificity and sensitivity. The remarkably high capability to catalyze oxidation reactions could allow the nanohybrid to replace conventional peroxidase-based immunoassay systems as part of new, rapid, robust and convenient assay systems which can be widely utilized for the identification of important target molecules.Enzyme-linked immunosorbent assays (ELISAs) have most widely been applied in immunoassays for several decades. However, several unavoidable limitations (e.g., instability caused by structural unfolding) of natural enzymes have hindered their widespread applications. Here, we describe a new nanohybrid consisting of Fe3O4 magnetic nanoparticles (MNPs) and platinum nanoparticles (Pt NPs), simultaneously immobilized on the surface of graphene oxide (GO). By synergistically integrating highly catalytically active Pt NPs and MNPs on GO whose frameworks possess high substrate affinity, the nanohybrid is able to achieve up to a 30-fold higher maximal reaction velocity (Vmax

  19. Improving Platinum Efficiency:. Nanoformulations

    NASA Astrophysics Data System (ADS)

    Carmona, Rolando; Liang, Xing-Jie

    2013-09-01

    Platinum-based drugs continue being the support of therapy for many different kinds of cancer. Cancer patients often present irreversible resistance to platinum after repeated treatment in clinic. Despite of the great efforts, chemoresistance (intrinsic or acquired) already is a major limitation in the management of this disease. In this review, the last current research on cancer characteristic and cancer chemical resistance is summarized, the major and novel strategies to reverse resistance to platinum- based drugs are discussed and this article mainly emphasizes the contribution of nanotechnology and combination therapies to target sites and reduce the cancer chemoresistance.

  20. A dual-targeting, p53-independent, apoptosis-inducing platinum(II) anticancer complex, [Pt(BDI(QQ))]Cl.

    PubMed

    Suntharalingam, Kogularamanan; Wilson, Justin J; Lin, Wei; Lippard, Stephen J

    2014-03-01

    The therapeutic index and cellular mechanism of action of [Pt(BDI(QQ))]Cl, a monocationic, square-planar platinum(II) complex, are reported. [Pt(BDI(QQ))]Cl was used to treat several cell lines, including wild type and cisplatin-resistant ovarian carcinoma cells (A2780 and A2780CP70) and non-proliferating lung carcinoma cells (A549). [Pt(BDI(QQ))]Cl selectively kills cancer cells over healthy cells and exhibits no cross-resistance with cisplatin. The mechanism of cell killing was established through detailed cell-based assays. [Pt(BDI(QQ))]Cl exhibits dual-threat capabilities, targeting nuclear DNA and mitochondria simultaneously. [Pt(BDI(QQ))]Cl induces DNA damage, leading to p53 enrichment, mitochondrial membrane potential depolarisation, and caspase-mediated apoptosis. [Pt(BDI(QQ))]Cl also accumulates in the mitochondria, resulting in direct mitochondrial damage. Flow cytometric studies demonstrated that [Pt(BDI(QQ))]Cl has no significant effect on cell cycle progression. Remarkably, p53-status is a not a determinant of [Pt(BDI(QQ))]Cl activity. In p53-null cells, [Pt(BDI(QQ))]Cl induces cell death through mitochondrial dysfunction. Cancers with p53-null status could therefore be targeted using [Pt(BDI(QQ))]Cl.

  1. Multifunctional iron platinum stealth immunomicelles: targeted detection of human prostate cancer cells using both fluorescence and magnetic resonance imaging

    PubMed Central

    Huber, Dale L.; Monson, Todd C.; Ali, Abdul-Mehdi S.; Bisoffi, Marco; Sillerud, Laurel O.

    2011-01-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are the most common type of contrast agents used in contrast agent-enhanced magnetic resonance imaging (MRI). Still, there is a great deal of room for improvement, and nanoparticles with increased MRI relaxivities are needed to increase the contrast enhancement in MRI applied to various medical conditions including cancer. We report the synthesis of superparamagnetic iron platinum nanoparticles (SIPPs) and subsequent encapsulation using PEGylated phospholipids to create stealth immunomicelles (DSPE-SIPPs) that can be specifically targeted to human prostate cancer cell lines and detected using both MRI and fluorescence imaging. SIPP cores and DSPE-SIPPs were 8.5 ± 1.6 nm and 42.9 ± 8.2 nm in diameter, respectively, and the SIPPs had a magnetic moment of 120 A m2/kg iron. J591, a monoclonal antibody against prostate specific membrane antigen (PSMA), was conjugated to the DSPE-SIPPs (J591-DSPE-SIPPs), and specific targeting of J591-DSPE-SIPPs to PSMA-expressing human prostate cancer cell lines was demonstrated using fluorescence confocal microscopy. The transverse relaxivity of the DSPE-SIPPs, measured at 4.7 Tesla, was 300.6 ± 8.5 s−1 mM−1, which is 13-fold better than commercially available SPIONs (23.8 ± 6.9 s−1 mM−1) and ~3-fold better than reported relaxivities for Feridex® and Resovist®. Our data suggest that J591-DSPE-SIPPs specifically target human prostate cancer cells in vitro, are superior contrast agents in T2-weighted MRI, and can be detected using fluorescence imaging. To our knowledge, this is the first report on the synthesis of multifunctional SIPP micelles and using SIPPs for the specific detection of prostate cancer. PMID:22121333

  2. Multifunctional iron platinum stealth immunomicelles: targeted detection of human prostate cancer cells using both fluorescence and magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Taylor, Robert M.; Huber, Dale L.; Monson, Todd C.; Ali, Abdul-Mehdi S.; Bisoffi, Marco; Sillerud, Laurel O.

    2011-10-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are the most common type of contrast agents used in contrast agent-enhanced magnetic resonance imaging (MRI). Still, there is a great deal of room for improvement, and nanoparticles with increased MRI relaxivities are needed to increase the contrast enhancement in MRI applied to various medical conditions including cancer. We report the synthesis of superparamagnetic iron platinum nanoparticles (SIPPs) and subsequent encapsulation using PEGylated phospholipids to create stealth immunomicelles (DSPE-SIPPs) that can be specifically targeted to human prostate cancer cell lines and detected using both MRI and fluorescence imaging. SIPP cores and DSPE-SIPPs were 8.5 ± 1.6 nm and 42.9 ± 8.2 nm in diameter, respectively, and the SIPPs had a magnetic moment of 120 A m2/kg iron. J591, a monoclonal antibody against prostate specific membrane antigen (PSMA), was conjugated to the DSPE-SIPPs (J591-DSPE-SIPPs), and specific targeting of J591-DSPE-SIPPs to PSMA-expressing human prostate cancer cell lines was demonstrated using fluorescence confocal microscopy. The transverse relaxivity of the DSPE-SIPPs, measured at 4.7 Tesla, was 300.6 ± 8.5 s-1 mM-1, which is 13-fold better than commercially available SPIONs (23.8 ± 6.9 s-1 mM-1) and 3-fold better than reported relaxivities for Feridex® and Resovist®. Our data suggest that J591-DSPE-SIPPs specifically target human prostate cancer cells in vitro, are superior contrast agents in T 2-weighted MRI, and can be detected using fluorescence imaging. To our knowledge, this is the first report on the synthesis of multifunctional SIPP micelles and using SIPPs for the specific detection of prostate cancer.

  3. Platinum hypersensitivity and desensitization.

    PubMed

    Miyamoto, Shingo; Okada, Rika; Ando, Kazumichi

    2015-09-01

    Platinum agents are drugs used for various types of cancer. With increased frequency of administration of platinum agents, hypersensitivity reactions appear more frequently, occurring in over 25% of cases from the seventh cycle or second line onward. It then becomes difficult to conduct treatment using these agents. Various approaches have been investigated to address hypersensitivity reactions to platinum agents. Desensitization, which gradually increases the concentration of the anticancer drug considered to be the antigen until the target dosage, has been reported as being particularly effective, with a success rate of 80-100%. The aims of this paper are to present the current findings regarding hypersensitivity reactions to platinum agents and to discuss attempts of using desensitization against hypersensitivity reactions worldwide. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Targeting Foxm1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer.

    PubMed

    Westhoff, Gina L; Chen, Yi; Teng, Nelson N H

    2017-06-01

    Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative real-time polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets. Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1, CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo. Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.

  5. Targeting FOXM1 Improves Cytotoxicity of Paclitaxel and Cisplatinum in Platinum-Resistant Ovarian Cancer.

    PubMed

    Westhoff, Gina L; Chen, Yi; Teng, Nelson N H

    2017-07-07

    Aberrantly activated FOXM1 (forkhead box protein M1) leading to uncontrolled cell proliferation and dysregulation of FOXM1 transcription network occurs in 84% of ovarian cancer cases. It was demonstrated that thiostrepton, a thiazole antibiotic, decreases FOXM1 expression. We aimed to determine if targeting the FOXM1 pathway with thiostrepton could improve the efficacy of paclitaxel and cisplatin in human ovarian cancer ascites cells ex vivo. Human ovarian cancer cell lines and patients' ascites cells were treated with paclitaxel, cisplatin, and thiostrepton or a combination for 48 hours, and cytotoxicity was assessed. Drug combination effects were determined by calculating the combination index values using the Chou and Talalay method. Quantitative reverse transcriptase-polymerase chain reaction was performed to determine changes in FOXM1 expression and its downstream targets. Ovarian cancer cell lines and the patients' ascites cancer cells had an overexpression of FOXM1 expression levels. Targeting FOXM1 with thiostrepton decreased FOXM1 mRNA expression and its downstream targets such as CCNB1 and CDC25B, leading to cell death in both cell lines and patients' ascites cancer cells. Furthermore, addition of thiostrepton to paclitaxel and cisplatin showed synergistic effects in chemoresistant ovarian cancer patients' ascites cells ex vivo. Targeting FOXM1 may lead to novel therapeutics for chemoresistant epithelial ovarian cancer.

  6. Methyl 6-Amino-6-deoxy-d-pyranoside-Conjugated Platinum(II) Complexes for Glucose Transporter (GLUT)-Mediated Tumor Targeting: Synthesis, Cytotoxicity, and Cellular Uptake Mechanism.

    PubMed

    Li, Taoli; Gao, Xiangqian; Yang, Liu; Shi, Yunli; Gao, Qingzhi

    2016-05-19

    Methyl 6-aminodeoxy-d-pyranoside-derived platinum(II) glycoconjugates were designed and synthesized based on the clinical drug oxaliplatin for glucose transporter (GLUT)-mediated tumor targeting. In addition to a substantial improvement in water solubility, the conjugates exhibited cytotoxicity similar to or higher than that of oxaliplatin in six different human cancer cell lines. GLUT-mediated transport of the complexes was investigated with a cell-based fluorescence competition assay and GLUT-inhibitor-mediated cytotoxicity analysis in a GLUT-overexpressing human colorectal adenocarcinoma (HT29) cell line. The antitumor effect of the aminodeoxypyranoside-conjugated platinum(II) complexes was found to depend significantly on the GLUT inhibitor, and the cellular uptake of the molecules was regulated by GLUT-mediated transport. The results from this study demonstrate the potential advantages of aminodeoxypyranosides as sugar motifs for glycoconjugation for Warburg-effect-targeted drug design. These fundamental results also support the potential of aminodeoxypyranoside-conjugated platinum(II) complexes as lead compounds for further preclinical evaluation.

  7. Glycosylated Platinum(IV) Complexes as Substrates for Glucose Transporters (GLUTs) and Organic Cation Transporters (OCTs) Exhibited Cancer Targeting and Human Serum Albumin Binding Properties for Drug Delivery.

    PubMed

    Ma, Jing; Wang, Qingpeng; Huang, Zhonglv; Yang, Xiande; Nie, Quandeng; Hao, Wenpei; Wang, Peng George; Wang, Xin

    2017-07-13

    Glycosylated platinum(IV) complexes were synthesized as substrates for GLUTs and OCTs for the first time, and the cytotoxicity and detailed mechanism were determined in vitro and in vivo. Galactoside Pt(IV), glucoside Pt(IV), and mannoside Pt(IV) were highly cytotoxic and showed specific cancer-targeting properties in vitro and in vivo. Glycosylated platinum(IV) complexes 5, 6, 7, and 8 (IC50 0.24-3.97 μM) had better antitumor activity of nearly 166-fold higher than the positive controls cisplatin (1a), oxaliplatin (3a), and satraplatin (5a). The presence of a hexadecanoic chain allowed binding with human serum albumin (HSA) for drug delivery, which not only enhanced the stability of the inert platinum(IV) prodrugs but also decreased their reduction by reductants present in human whole blood. Their preferential accumulation in cancer cells compared to noncancerous cells (293T and 3T3 cells) suggested that they were potentially safe for clinical therapeutic use.

  8. Exploiting developments in nanotechnology for the preferential delivery of platinum-based anti-cancer agents to tumours: targeting some of the hallmarks of cancer.

    PubMed

    Parker, James P; Ude, Ziga; Marmion, Celine J

    2016-01-01

    Platinum drugs as anti-cancer therapeutics are held in extremely high regard. Despite their success, there are drawbacks associated with their use; their dose-limiting toxicity, their limited activity against an array of common cancers and patient resistance to Pt-based therapeutic regimes. Current investigations in medicinal inorganic chemistry strive to offset these shortcomings through selective targeting of Pt drugs and/or the development of Pt drugs with new or multiple modes of action. A comprehensive overview showcasing how liposomes, nanocapsules, polymers, dendrimers, nanoparticles and nanotubes may be employed as vehicles to selectively deliver cytotoxic Pt payloads to tumour cells is provided.

  9. Design, Synthesis, and Characterization of Folate-Targeted Platinum-Loaded Theranostic Nanoemulsions for Therapy and Imaging of Ovarian Cancer.

    PubMed

    Patel, Niravkumar R; Piroyan, Aleksandr; Nack, Abbegial H; Galati, Corin A; McHugh, Mackenzi; Orosz, Samantha; Keeler, Amanda W; O'Neal, Sara; Zamboni, William C; Davis, Barbara; Coleman, Timothy P

    2016-06-06

    Platinum (Pt) based chemotherapy is widely used to treat many types of cancer. Pt therapy faces challenges such as dose limiting toxicities, cumulative side effects, and multidrug resistance. Nanoemulsions (NEs) have tremendous potential in overcoming these challenges as they can be designed to improve circulation time, limit non-disease tissue uptake, and enhance tumor uptake by surface modification. We designed novel synthesis of three difattyacid platins, dimyrisplatin, dipalmiplatin, and distearyplatin, suitable for encapsulation in the oil core of an NE. The dimyrisplatin, dipalmiplatin, and distearyplatin were synthesized, characterized, and loaded into the oil core of our NEs, NMI-350, NMI-351, and NMI-352 respectively. Sequestration of the difattyacid platins was accomplished through high energy microfluidization. To target the NE, FA-PEG3400-DSPE was incorporated into the surface during microfluidization. The FA-NEs selectively bind the folate receptor α (FR-α) and utilize receptor mediated endocytosis to deliver Pt past cell surface resistance mechanisms. FR-α is overexpressed in a number of oncological conditions including ovarian cancer. The difattyacid platins, lipidated Gd-DTPA, and lipidated folate were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), and elemental analysis. NEs were synthesized using high shear microfluidization process and characterized for size, zeta-potential, and loading efficiency. In vitro cytotoxicity was determined using KB-WT (Pt-sensitive) and KBCR-1000 (Pt-resistant) cancer cells and measured by MTT assay. Pharmacokinetic profiles were studied in CD-1 mice. NEs loaded with difattyacid platins are highly stable and had size distribution in the range of ∼120 to 150 nm with low PDI. Cytotoxicity data indicates the longer the fatty acid chains, the less potent the NEs. The inclusion of C6-ceramide, an apoptosis enhancer, and surface functionalization with folate molecules significantly increased

  10. DNA-based aptamer fails as a simultaneous cancer targeting agent and drug delivery vehicle for a phenanthroline-based platinum(II) complex.

    PubMed

    McGinely, Nicola L; Plumb, Jane A; Wheate, Nial J

    2013-11-01

    The sgc8c aptamer is a 41-base DNA oligonucleotide that binds to leukaemia cells with high affinity and specificity. In this work we examined the utility of this aptamer as both a delivery vehicle and an active targeting agent for an inert platinum complex [(1,10-phenathroline)(ethylenediamine)platinum(II)](2+). The aptamer forms a stem-and-loop confirmation as determined by circular dichroism. This conformation is adopted in both water and phosphate buffered saline solutions. The metal complex binds through intercalation into the aptamer's double helical stem with a binding constant of approximately 4.3 × 10(4) M(-1). Binding of the metal complex to the aptamer had a significant effect on the aptamer's global conformation, and increased its melting temperature by 28°C possibly through lengthening and stiffening of the aptamer stem. The effect of the aptamer on the metal complex's cytotoxicity and cellular uptake was determined using in vitro assays with the target leukaemia cell line CCRF-CEM and the off-target ovarian cancer cell lines A2780 and A2780cp70. The aptamer has little inherent cytotoxicity and when used to deliver the metal complex results in a significant decrease in the metal complex's cytotoxicity and uptake. The reason(s) for the poor uptake and activity may be due to the change in aptamer conformation which affects its ability to recognise leukaemia cells.

  11. Role of miR-196 and its target gene HoxB8 in the development and proliferation of human colorectal cancer and the impact of neoadjuvant chemotherapy with FOLFOX4 on their expression

    PubMed Central

    Shen, Songfei; Pan, Jie; Lu, Xingrong; Chi, Pan

    2016-01-01

    The present study aimed to investigate the interaction between miR-196 and its target gene homeobox B8 (HoxB8) in colorectal cancer (CRC) cells, and the sensitivity of miR-196 and HoxB8 to fluorouracil, leucovorin and oxaliplatin (FOLFOX4) chemotherapy (1,200 mg/m2 fluorouracil, 200 mg/m2 leucovorin and 85 mg/m2 oxaliplatin). In total, 80 tissue samples were collected in the present study. In total, 50 patients undergoing preoperative chemotherapy completed at least 3 cycles (2 weeks per cycle) of 85 mg/m2 oxaliplatin (day 1) combined with a 2 h injection of 200 mg/m2 leucovorin (days 1 and 2), a bolus injection of 400 mg/m2 and 44 h continuous intravenous infusion of 1,200 mg/m2 fluorouracil. Complete response and partial response were included in the chemotherapy sensitive group (25 patients), and stable disease and progressive disease were included in the chemotherapy resistant group (25 patients). In addition, 30 patients without preoperative chemotherapy were examined for mRNA and protein expression of miR-196 and HoxB8. The expression of the mRNA and protein of miR-196 and HoxB8 was analyzed in 30 CRC and normal mucosa tissue samples. In addition, the expression of the mRNA and protein of miR-196 and HoxB8 was measured in 50 tissue samples obtained from patients that had received FOLFOX4 neoadjuvant chemotherapy. The expression levels of miR-196 and HoxB8 mRNA in CRC tissues were significantly increased compared with the corresponding normal mucosa tissue (P<0.05). The miR-196 mRNA was significantly correlated with lymph node metastasis, tumor stage and distant metastasis (P<0.05). miR-196 was indicated to be negatively correlated with HoxB8 mRNA expression (r=−0.458; P<0.05). The relative amount of miR-196 in the chemotherapy-sensitive group of patients was 0.949±0.691, which was increased compared with the chemotherapy-resistant group (0.345±0.536; P<0.01). The relative level of HoxB8 mRNA in the chemotherapy-sensitive group was 0.490±0.372, which was

  12. Chemical approach to positional isomers of glucose-platinum conjugates reveals specific cancer targeting through glucose-transporter mediated uptake in vitro and in vivo

    PubMed Central

    Patra, Malay; Awuah, Samuel G.; Lippard, Stephen J.

    2016-01-01

    Glycoconjugation is a promising strategy for specific targeting of cancer. In this study, we investigated the effect of D-glucose substitution position on the biological activity of glucose-platinum conjugates (Glc-Pts). We synthesized and characterized all possible positional isomers (C1α, C1β, C2, C3, C4 and C6) of a Glc-Pt. The synthetic routes presented here could in principle be extended to prepare glucose-conjugates with different active ingredients than platinum. The biological activities of the compounds were evaluated both in vitro and in vivo. We discovered that variation in position of substitution of D-glucose not only alters the cellular uptake and cytotoxicity profile but also the GLUT1 specificity of resulting glycoconjugates, where GLUT1 is glucose transporter 1. The C1α- and C2-substituted Glc-Pts (1α and 2) accumulate in cancer cells most efficiently compared to the others, whereas the C3-Glc-Pt (3) is taken up least efficiently. Compounds 1α and 2 are more potent compared to 3 in DU145 cells. The α- and β-anomer of the C1-Glc-Pt also differ significantly in their cellular uptake and activity profiles. No significant differences in uptake of the Glc-Pts were observed in noncancerous RWPE2 cells. The GLUT1 specificity of the Glc-Pts was evaluated by determining the cellular uptake in the absence and presence of the GLUT1 inhibitor cytochalasin B, and by comparing their anticancer activity in DU145 cells and a GLUT1 knockdown cell line. The results reveal that C2-substituted Glc-Pt 2 has the highest GLUT1 specific internalization, which also reflects the best cancer targeting ability. In a syngeneic breast cancer mouse model overexpressing GLUT1, compound 2 showed antitumor efficacy and selective uptake in tumors with no observable toxicity. This study thus reveals the synthesis of all positional isomers of D-glucose substitution for platinum warhead with detailed glycotargeting characterization in cancer. PMID:27570149

  13. Nucleolar Targeting by Platinum: p53-Independent Apoptosis Follows rRNA Inhibition, Cell-Cycle Arrest, and DNA Compaction

    PubMed Central

    2015-01-01

    TriplatinNC is a highly positively charged, substitution-inert derivative of the phase II clinical anticancer drug, BBR3464. Such substitution-inert complexes form a distinct subset of polynuclear platinum complexes (PPCs) interacting with DNA and other biomolecules through noncovalent interactions. Rapid cellular entry is facilitated via interaction with cell surface glycosoaminoglycans and is a mechanism unique to PPCs. Nanoscale secondary ion mass spectrometry (nanoSIMS) showed rapid distribution within cytoplasmic and nucleolar compartments, but not the nucleus. In this article, the downstream effects of nucleolar localization are described. In human colon carcinoma cells, HCT116, the production rate of 47S rRNA precursor transcripts was dramatically reduced as an early event after drug treatment. Transcriptional inhibition of rRNA was followed by a robust G1 arrest, and activation of apoptotic proteins caspase-8, -9, and -3 and PARP-1 in a p53-independent manner. Using cell synchronization and flow cytometry, it was determined that cells treated while in G1 arrest immediately, but cells treated in S or G2 successfully complete mitosis. Twenty-four hours after treatment, the majority of cells finally arrest in G1, but nearly one-third contained highly compacted DNA; a distinct biological feature that cannot be associated with mitosis, senescence, or apoptosis. This unique effect mirrored the efficient condensation of tRNA and DNA in cell-free systems. The combination of DNA compaction and apoptosis by TriplatinNC treatment conferred striking activity in platinum-resistant and/or p53 mutant or null cell lines. Taken together, our results support that the biological activity of TriplatinNC reflects reduced metabolic deactivation (substitution-inert compound not reactive to sulfur nucleophiles), high cellular accumulation, and novel consequences of high-affinity noncovalent DNA binding, producing a new profile and a further shift in the structure

  14. Detailed analysis of targeted gene mutations caused by the Platinum-Fungal TALENs in Aspergillus oryzae RIB40 strain and a ligD disruptant.

    PubMed

    Mizutani, Osamu; Arazoe, Takayuki; Toshida, Kenji; Hayashi, Risa; Ohsato, Shuichi; Sakuma, Tetsushi; Yamamoto, Takashi; Kuwata, Shigeru; Yamada, Osamu

    2017-03-01

    Transcription activator-like effector nucleases (TALENs), which can generate DNA double-strand breaks at specific sites in the desired genome locus, have been used in many organisms as a tool for genome editing. In Aspergilli, including Aspergillus oryzae, however, the use of TALENs has not been validated. In this study, we performed genome editing of A. oryzae wild-type strain via error of nonhomologous end-joining (NHEJ) repair by transient expression of high-efficiency Platinum-Fungal TALENs (PtFg TALENs). Targeted mutations were observed as various mutation patterns. In particular, approximately half of the PtFg TALEN-mediated deletion mutants had deletions larger than 1 kb in the TALEN-targeting region. We also conducted PtFg TALEN-based genome editing in A. oryzae ligD disruptant (ΔligD) lacking the ligD gene involved in the final step of the NHEJ repair and found that mutations were still obtained as well as wild-type. In this case, the ratio of the large deletions reduced compared to PtFg TALEN-based genome editing in the wild-type. In conclusion, we demonstrate that PtFg TALENs are sufficiently functional to cause genome editing via error of NHEJ in A. oryzae. In addition, we reveal that genome editing using TALENs in A. oryzae tends to cause large deletions at the target region, which were partly suppressed by deletion of ligD.

  15. Platinum stable isotopes in ferromanganese crust and nodules

    NASA Astrophysics Data System (ADS)

    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 (< ±1) in the stable isotopic composition of marine platinum, raising the potential of adding platinum to the growing arsenal of paleoceanographic tracers. A method has been developed to measure the platinum isotopic composition using double spike MC-ICPMS analysis [2]and applied to a global suite of modern Fe-Mn crust and nodules. Combining synchrotron XAFS analyses of platinum adsorbed onto Fe-Mn oxide and oxyhydroxide surfaces to determine oxidation state and bonding environment, with platinum stable isotopic measurements allowing us to evaluate both platinum incorporation onto these sediments and the associated degree of platinum isotopic fractionation. 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.

  16. In Vitro and In Vivo Studies of Non-Platinum-Based Halogenated Compounds as Potent Antitumor Agents for Natural Targeted Chemotherapy of Cancers

    PubMed Central

    Lu, Qing-Bin; Zhang, Qin-Rong; Ou, Ning; Wang, Chun-Rong; Warrington, Jenny

    2015-01-01

    Based on a molecular-mechanism-based anticancer drug discovery program enabled by an innovative femtomedicine approach, we have found a previously unknown class of non-platinum-based halogenated molecules (called FMD compounds) as potent antitumor agents for effective treatment of cancers. Here, we present in vitro and in vivo studies of the compounds for targeted chemotherapy of cervical, breast, ovarian, and lung cancers. Our results show that these FMD agents led to DNA damage, cell cycle arrest in the S phase, and apoptosis in cancer cells. We also observed that such a FMD compound caused an increase of reduced glutathione (GSH, an endogenous antioxidant) levels in human normal cells, while it largely depleted GSH in cancer cells. We correspondingly found that these FMD agents exhibited no or little toxicity toward normal cells/tissues, while causing significant cytotoxicity against cancer cells, as well as suppression and delay in tumor growth in mouse xenograft models of cervical, ovarian, breast and lung cancers. These compounds are therefore a previously undiscovered class of potent antitumor agents that can be translated into clinical trials for natural targeted chemotherapy of multiple cancers. PMID:26351651

  17. Anticancer platinum (IV) prodrugs with novel modes of activity.

    PubMed

    Chin, Chee Fei; Wong, Daniel Yuan Qiang; Jothibasu, Ramasamy; Ang, Wee Han

    2011-01-01

    Over the past four decades, the search for improved platinum drugs based on the classical platinum (II)-diam(m)ine pharmacophore has yielded only a handful of successful candidates. New methodologies centred on platinum (IV) complexes, with better stability and expanded coordination spheres, offer the possibility of overcoming limitations inherent to platinum (II) drugs. In this review, novel strategies of targeting and killing cancer cells using platinum (IV) constructs are discussed. These approaches exploit the unique electrochemical characteristics and structural attributes of platinum (IV) complexes as a means of developing anticancer prodrugs that can target and selectively destroy cancer cells. Anticancer platinum (IV) prodrugs represent promising new strategies as targeted chemotherapeutic agents in the ongoing battle against cancer.

  18. Au-Pt alloy nanoparticles obtained by nanosecond laser irradiation of gold and platinum bulk targets in an ethylene glycol solution

    NASA Astrophysics Data System (ADS)

    Moniri, Samira; Reza Hantehzadeh, Mohammad; Ghoranneviss, Mahmood; Asadi Asadabad, Mohsen

    2017-07-01

    Au-Pt alloy nanoparticles (NPs) of different compositions ( Au0Pt100 , Au30Pt70 , Au50Pt50 , Au70Pt30 , and Au100Pt0 were obtained using the nanosecond laser ablation of gold and platinum bulk targets in ethylene glycol, followed by mixing highly monodisperse Au and Pt nanocolloids, for the first time. UV-vis absorption spectra of NPs showed that by increasing the Au content in the Au-Pt NPs, the surface plasmon resonance (SPR) peak red-shifted, from 260 to 573nm in a nonlinear way. In addition, the mean crystalline size, crystal structure, d-spacing, and lattice parameters of NPs were estimated from the XRD spectra. Microscopy studies revealed the most NPs have a spherical or near-spherical shape, and the average sizes of Au0Pt100 , Au30Pt70 , Au50Pt50 , Au70Pt30 , and Au100Pt0 NPs were calculated to be 12.50, 14.15, 18.53, 19.29, and 26.38nm, respectively. Also, the chemical identity of the molecules adhering to the NPs surface was considered by Raman and FT-IR spectroscopy techniques. Among different synthesis methods, the demonstrated technique allows easy synthesis of alloy NPs in aqueous media at room temperature with no formation of by-products.

  19. Radiation and platinum drug interaction.

    PubMed

    Nias, A H

    1985-09-01

    Platinum drugs have chemical as well as biochemical and biological effects on cells, all of which may interact with radiation effects. They inhibit recovery from sublethal and potentially lethal radiation damage. They produce a pattern of chromosome aberrations analogous to that from alkylating agents. Cellular sensitivity to platinum is increased when glutathione levels are reduced, just as is radiosensitivity. There is a pattern of drug sensitivity throughout the phases of the cell cycle which is different from that for radiosensitivity. 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.

  20. Extended Platinum Nanotubes as Fuel Cell Catalysts

    SciTech Connect

    Alia, S.; Pivovar, B. S.; Yan, Y.

    2012-01-01

    Energy consumption has relied principally on fossil fuels as an energy source; fuel cells, however, can provide a clean and sustainable alternative, an answer to the depletion and climate change concerns of fossil fuels. Within proton exchange membrane fuel cells, high catalyst cost and poor durability limit the commercial viability of the device. Recently, platinum nanotubes (PtNTs) were studied as durable, active catalysts, providing a platform to meet US Department of Energy vehicular activity targets.[1] Porous PtNTs were developed to increase nanotube surface area, improving mass activity for oxygen reduction without sacrificing durability.[2] Subsurface platinum was then replaced with palladium, forming platinum-coated palladium nanotubes.[3] By forming a core shell structure, platinum utilization was increased, reducing catalyst cost. Alternative substrates have also been examined, modifying platinum surface facets and increasing oxygen reduction specific activity. Through modification of the PtNT platform, catalyst limitations can be reduced, ensuring a commercially viable device.

  1. A triple-amplification colorimetric assay for antibiotics based on magnetic aptamer-enzyme co-immobilized platinum nanoprobes and exonuclease-assisted target recycling.

    PubMed

    Miao, Yangbao; Gan, Ning; Ren, Hong-Xia; Li, Tianhua; Cao, Yuting; Hu, Futao; Yan, Zhongdan; Chen, Yinji

    2015-11-21

    Herein, an ultrasensitive and selective colorimetric assay for antibiotics, using chloramphenicol (CAP) as the model analyte, was developed based on magnetic aptamer-HRP-platinum composite probes and exonuclease-assisted target recycling. The composite probes were prepared through immunoreactions between the double stranded DNA antibody (anti-DNA) labeled on core-shell Fe3O4@Au nanoparticles (AuMNP-anti-DNA) as the capture probe, and the double stranded aptamer (aptamer hybrid with its complementary oligonucleotides) labeled on Pt@HRP nanoparticles as the nanotracer (ds-Apt-HRP-PtNPs). When the CAP samples were incubated with the probes for 30 min at room temperature, they could be captured by the aptamer to form a nanotracer-CAP complex, which was then released into the supernatant after magnetic separation. This is because the anti-DNA on the capture probes cannot recognize the single strand aptamer-CAP complex. The exonuclease I (Exo I) added into the supernatant can further digest the aptamer-CAP from the 3'-end of the aptamer and the CAP in the aptamer-CAP complex can be released again, which can further participate in a new cycling process to react with the probes. Pt and HRP in the nanotracer could both catalyze and dual amplify the absorbance at 650 nm ascribed to the 3,3',5,5'-tetramethylbenzidine (TMB)-H2O2 system. Moreover, Exo I can assist the target recycling, which can further amplify the signal. Thus, the triple amplified signal can be quantified by ultraviolet-visible spectroscopy. The experimental results showed that the CAP detection possessed a linear range of 0.001-10 ng mL(-1) and a detection limit of 0.0003 ng mL(-1) (S/N = 3). The assay was successfully employed to detect CAP in milk, which is much more facile, time saving, and sensitive than the commercial ELISA kits.

  2. Altered glutamine metabolism in platinum resistant ovarian cancer

    PubMed Central

    Hudson, Chantelle D.; Savadelis, Alyssa; Nagaraj, Anil Belur; Joseph, Peronne; Avril, Stefanie; DiFeo, Analisa; Avril, Norbert

    2016-01-01

    Ovarian cancer is characterized by an increase in cellular energy metabolism, which is predominantly satisfied by glucose and glutamine. Targeting metabolic pathways is an attractive approach to enhance the therapeutic effectiveness and to potentially overcome drug resistance in ovarian cancer. In platinum-sensitive ovarian cancer cell lines the metabolism of both, glucose and glutamine was initially up-regulated in response to platinum treatment. In contrast, platinum-resistant cells revealed a significant dependency on the presence of glutamine, with an upregulated expression of glutamine transporter ASCT2 and glutaminase. This resulted in a higher oxygen consumption rate compared to platinum-sensitive cell lines reflecting the increased dependency of glutamine utilization through the tricarboxylic acid cycle. The important role of glutamine metabolism was confirmed by stable overexpression of glutaminase, which conferred platinum resistance. Conversely, shRNA knockdown of glutaminase in platinum resistant cells resulted in re-sensitization to platinum treatment. Importantly, combining the glutaminase inhibitor BPTES with platinum synergistically inhibited platinum sensitive and resistant ovarian cancers in vitro. Apoptotic induction was significantly increased using platinum together with BPTES compared to either treatment alone. Our findings suggest that targeting glutamine metabolism together with platinum based chemotherapy offers a potential treatment strategy particularly in drug resistant ovarian cancer. PMID:27191653

  3. Altered glutamine metabolism in platinum resistant ovarian cancer.

    PubMed

    Hudson, Chantelle D; Savadelis, Alyssa; Nagaraj, Anil Belur; Joseph, Peronne; Avril, Stefanie; DiFeo, Analisa; Avril, Norbert

    2016-07-05

    Ovarian cancer is characterized by an increase in cellular energy metabolism, which is predominantly satisfied by glucose and glutamine. Targeting metabolic pathways is an attractive approach to enhance the therapeutic effectiveness and to potentially overcome drug resistance in ovarian cancer. In platinum-sensitive ovarian cancer cell lines the metabolism of both, glucose and glutamine was initially up-regulated in response to platinum treatment. In contrast, platinum-resistant cells revealed a significant dependency on the presence of glutamine, with an upregulated expression of glutamine transporter ASCT2 and glutaminase. This resulted in a higher oxygen consumption rate compared to platinum-sensitive cell lines reflecting the increased dependency of glutamine utilization through the tricarboxylic acid cycle. The important role of glutamine metabolism was confirmed by stable overexpression of glutaminase, which conferred platinum resistance. Conversely, shRNA knockdown of glutaminase in platinum resistant cells resulted in re-sensitization to platinum treatment. Importantly, combining the glutaminase inhibitor BPTES with platinum synergistically inhibited platinum sensitive and resistant ovarian cancers in vitro. Apoptotic induction was significantly increased using platinum together with BPTES compared to either treatment alone. Our findings suggest that targeting glutamine metabolism together with platinum based chemotherapy offers a potential treatment strategy particularly in drug resistant ovarian cancer.

  4. Galactose conjugated platinum(II) complex targeting the Warburg effect for treatment of non-small cell lung cancer and colon cancer.

    PubMed

    Wu, Meng; Li, Hong; Liu, Ran; Gao, Xiangqian; Zhang, Menghua; Liu, Pengxing; Fu, Zheng; Yang, Jinna; Zhang-Negrerie, Daisy; Gao, Qingzhi

    2016-03-03

    Malignant neoplasms exhibit a higher rate of glycolysis than normal cells; this is known as the Warburg effect. To target it, a galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-chloromalonato-platinum(II) complex (Gal-Pt) was designed, synthesized, and evaluated in five human cancer cell lines and against two different xenograft tumour models. Gal-Pt exhibits much higher aqueous solubility (over 25 times) and improved cytotoxicity than oxaliplatin, especially in human colon (HT29) and lung (H460) cancer cell lines. The safety profile of Gal-Pt was investigated in vivo by exploring the maximum tolerated dose (MTD) and animal mortality rate. The ratios of the animal lethal dosage values to the cytotoxicity in HT29 (LD50/IC50) showed that Gal-Pt was associated with an increased therapeutic index by over 30-fold compared to cisplatin and oxaliplatin. We evaluated in vivo antitumor activity by single agent intravenous treatment comparison studies of Gal-Pt (50 mg/kg as 65% MTD) and cisplatin (3 mg/kg, as 80% MTD) in a H460 lung cancer xenograft model, and with oxaliplatin (7 mg/kg, as 90% MTD) in a HT29 colon cancer xenograft model. The results show that Gal-Pt was more efficacious against H460 than cisplatin, and had superior potency in HT29 cells compared to oxaliplatin under nontoxic dosage conditions. The dependency between cytotoxicity of Gal-Pt and glucose transporters (GLUTs) was investigated by using quercetin as an inhibitor of GLUTs in HT29 cells. The cytotoxic potency of Gal-Pt was highly reduced by the inhibitor, suggesting that the uptake of Gal-Pt was regulated by glucose transporters. The GLUT mediated transportability and cellular uptake of Gal-Pt was also demonstrated using a fluorescent glucose bioprobe in HT29 competition assay.

  5. PLATINUM AND FUEL CELLS

    EPA Science Inventory

    Platinum requirements for fuel cell vehicles (FCVS) have been identified as a concern and possible problem with FCV market penetration. Platinum is a necessary component of the electrodes of fuel cell engines that power the vehicles. The platinum is deposited on porous electrodes...

  6. PLATINUM AND FUEL CELLS

    EPA Science Inventory

    Platinum requirements for fuel cell vehicles (FCVS) have been identified as a concern and possible problem with FCV market penetration. Platinum is a necessary component of the electrodes of fuel cell engines that power the vehicles. The platinum is deposited on porous electrodes...

  7. 32 CFR 196.310 - Recruitment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Recruitment. 196.310 Section 196.310 National... Discrimination on the Basis of Sex in Admission and Recruitment Prohibited § 196.310 Recruitment. (a) Nondiscriminatory recruitment. A recipient to which §§ 196.300 through 196.310 apply shall not discriminate on the...

  8. VEGF/VEGFR-2 upregulates EZH2 expression in lung adenocarcinoma cells and EZH2 depletion enhances the response to platinum-based and VEGFR-2–targeted therapy

    PubMed Central

    Riquelme, Erick; Suraokar, Milind; Behrens, Carmen; Lin, Heather Y.; Girard, Luc; Nilsson, Monique B.; Simon, George; Wang, Jing; Coombes, Kevin R.; Lee, J. Jack; Hong, Waun Ki; Heymach, John; Minna, John D.; Wistuba, Ignacio I.

    2014-01-01

    Purpose Investigate the mechanisms of regulation and role associated with EZH2 expression in lung cancer cells. Experimental Design We investigated the mechanisms of EZH2 expression associated with the vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR-2) pathway. Furthermore, we sought to determine the role of EZH2 in response of lung adenocarcinoma to platinum-based chemotherapy, as well as the effect of EZH2 depletion on VEGFR-2–targeted therapy in lung adenocarcinoma cell lines. Additionally, we characterized EZH2 expression in lung adenocarcinoma specimens and correlated it with patients’ clinical characteristics. Results In this study, we demonstrate that VEGF/VEGFR-2 activation induces expression of EZH2 through the upregulation of E2F3 and HIF-1α, and downregulated expression of miR-101. EZH2 depletion by treatment with 3-deazaneplanocin A and knockdown by siRNA decreased the expression of EZH2 and H3K27me3, increased PARP-C level, reduced cell proliferation and migration, and increased sensitivity of the cells to treatment with cisplatin and carboplatin. Additionally, high EZH2 expression was associated with poor overall survival in patients who received platinum-based adjuvant therapy, but not in patients who did not receive this therapy. Furthermore, we demonstrated for the first time that the inhibition of EZH2 greatly increased the sensitivity of lung adenocarcinoma cells to the anti-VEGFR-2 drug AZD2171. Conclusion Our results suggest that VEGF/VEGFR-2 pathway plays a role in regulation of EZH2 expression via E2F3, HIF-1α and miR-101. EZH2 depletion decreases the malignant potential of lung adenocarcinoma and sensitivity of the cells to both platinum-based and VEGFR-2–targeted therapy. PMID:24850841

  9. Independent regulation of vertebral number and vertebral identity by microRNA-196 paralogs

    PubMed Central

    Wong, Siew Fen Lisa; Agarwal, Vikram; Mansfield, Jennifer H.; Denans, Nicolas; Schwartz, Matthew G.; Prosser, Haydn M.; Pourquié, Olivier; Bartel, David P.; Tabin, Clifford J.; McGlinn, Edwina

    2015-01-01

    The Hox genes play a central role in patterning the embryonic anterior-to-posterior axis. An important function of Hox activity in vertebrates is the specification of different vertebral morphologies, with an additional role in axis elongation emerging. The miR-196 family of microRNAs (miRNAs) are predicted to extensively target Hox 3′ UTRs, although the full extent to which miR-196 regulates Hox expression dynamics and influences mammalian development remains to be elucidated. Here we used an extensive allelic series of mouse knockouts to show that the miR-196 family of miRNAs is essential both for properly patterning vertebral identity at different axial levels and for modulating the total number of vertebrae. All three miR-196 paralogs, 196a1, 196a2, and 196b, act redundantly to pattern the midthoracic region, whereas 196a2 and 196b have an additive role in controlling the number of rib-bearing vertebra and positioning of the sacrum. Independent of this, 196a1, 196a2, and 196b act redundantly to constrain total vertebral number. Loss of miR-196 leads to a collective up-regulation of numerous trunk Hox target genes with a concomitant delay in activation of caudal Hox genes, which are proposed to signal the end of axis extension. Additionally, we identified altered molecular signatures associated with the Wnt, Fgf, and Notch/segmentation pathways and demonstrate that miR-196 has the potential to regulate Wnt activity by multiple mechanisms. By feeding into, and thereby integrating, multiple genetic networks controlling vertebral number and identity, miR-196 is a critical player defining axial formulae. PMID:26283362

  10. Platinum-containing compound platinum pyrithione is stronger and safer than cisplatin in cancer therapy

    PubMed Central

    Zang, Dan; Lan, Xiaoying; Liao, Siyan; Yang, Changshan; Zhang, Peiquan; Wu, Jinjie; Li, Xiaofen; Liu, Ningning; Liao, Yuning; Huang, Hongbiao; Shi, Xianping; Jiang, Lili; Liu, Xiuhua; He, Zhimin; Wang, Xuejun; Liu, Jinbao

    2017-01-01

    DNA is the well-known molecular target of current platinum-based anticancer drugs; consequently, their clinical use is severely restricted by their systemic toxicities and drug resistance originating from non-selective DNA damage. Various strategies have been developed to circumvent the shortcomings of platinum-based chemotherapy but the inherent problem remains unsolved. Here we report that platinum pyrithione (PtPT), a chemically well-characterized synthetic complex of platinum, inhibits proteasome function and thereby exhibits greater and more selective cytotoxicity to multiple cancer cells than cisplatin, without showing discernible DNA damage both in vitro and in vivo. Moreover, unlike the classical proteasome inhibitor bortezomib/Velcade which inhibits the proteasome via blocking the peptidase activity of 20S proteasomes, PtPT primarily deactivates 26S proteasome-associated deubiquitinases USP14 and UCHL5. Furthermore, PtPT can selectively induce cytotoxicity and proteasome inhibition in cancer cells from leukemia patients but not peripheral blood mononuclear cells from healthy humans. In nude mice, PtPT also remarkably inhibited tumor xenograft growth, without showing the adverse effects that were induced by cisplatin. Hence, we have discovered a new platinum-based anti-tumor agent PtPT which targets 26S proteasome-associated deubiquitinases rather than DNA in the cell and thereby exerts safer and more potent anti-tumor effects, identifying a highly translatable new platinum-based anti-cancer strategy. PMID:27381943

  11. Antidepressants and platinum drugs.

    PubMed

    Engelmann, Brigitte J; Ryan, John J; Farrell, Nicholas P

    2014-01-01

    Antidepressants are frequently prescribed concurrently with anti-cancer drugs and may have synergistic, additive or antagonistic effects. The present work investigated the effect of antidepressants on the cytotoxicity of platinum agents cisplatin, carboplatin and oxaliplatin. The cytotoxicity of platinum drugs alone or in combination with antidepressants was measured in HCT116 wild-type (wt), HCT116 (p53 -/-), HT-29, SKOV3 and A2780 cells using an apoptosis-based assay. The effect of antidepressants on platinum cytotoxicity is both cell type- and drug dependent. Mostly additive effects were observed. Desipramine and fluoxetine caused the greatest effects, with cisplatin in general being most sensitive to their presence. There is little effect of p53 status on the drug-drug interaction while the calmodulin inhibitor W7 augmented cisplatin cytotoxicity relative to carboplatin and oxaliplatin. The drug-drug interaction between antidepressants and platinum anti-cancer agents requires detailed evaluation for optimization of patient care.

  12. Drug Delivery Systems for Platinum Drugs

    NASA Astrophysics Data System (ADS)

    Huynh, Vien T.; Scarano, Wei; Stenzel, Martina H.

    2013-09-01

    Since the discovery of cisplatin, drugs based on platinum, have made a significant impact on the treatment of various cancers. The administration of platinum drugs is however accompanied by significant side effects. This chapter discusses the types of drug delivery systems that have been developed in order to enable the targeted delivery while maintaining controlled temporal supply of the drug. The sizes of carriers range from nanometer to micrometer sized particles. The most common types of drug carriers are micelles, liposomes, nanoparticles, and dendrimers, but also a few microspheres have been developed. Most striking aspect of the delivery of platinum drugs is the possibility of physical encapsulation but also the binding of the drug to the polymer carrier coordinate covalent bond. Since platinum drugs have typically two permanent and two leaving ligands, the polymer can be part of either ligand. As the leaving ligand, the platinum drug is released often as cisplatin. If the polymer provides the functionality for the permanent ligand, a new macromolecular drug has been formed. In addition to the attachment of pt(II) drugs, recent offorts are devoted to the conjugation via the Pt((IV) prodrug.

  13. MicroRNA 196B regulates FAS-mediated apoptosis in colorectal cancer cells

    PubMed Central

    Kang, In-Hong; Park, Won Cheol; Seo, Geom-Seog; Choi, Suck-Chei; Kim, Hun-Soo; Moon, Hyung-Bae; Yun, Ki-Jung; Chae, Soo-Cheon

    2015-01-01

    Using miRNA microarray analysis, we identified 31 miRNAs that were significantly up-regulated or down-regulated in colon cancer tissues. We chose MIR196B, which was specifically up-regulated in colon cancer, for further study. We identified 18 putative MIR196B target genes by comparing between the mRNAs down-regulated in MIR196B-overexpressed cells and the assumed MIR196B target genes predicted by public bioinformatics tools. The association between MIR196B and FAS was verified in this study. FAS expression was constitutively elevated in normal human colorectal tissues. However, its expression was often reduced in human colorectal cancer. The decrease in FAS expression could be responsible for the reduction of apoptosis in colorectal cancer cells. In colorectal cancer tissue, we showed that MIR196B up-regulation was mutually followed by down regulation of FAS expression. We also showed that MIR196B directly repressed FAS expression in colorectal cells. Furthermore, anti-MIR196B up-regulated FAS expression and increased apoptosis in colorectal cancer cell lines. Our results suggest that the up-regulation of MIR196B modulates apoptosis in colorectal cancer cells by partially repressing FAS expression and that anti-MIR196B could be a potential candidate as an anti-cancer drug in colorectal cancer therapy. PMID:25605245

  14. Functionalization of Platinum Complexes for Biomedical Applications.

    PubMed

    Wang, Xiaoyong; Wang, Xiaohui; Guo, Zijian

    2015-09-15

    Platinum-based anticancer drugs are the mainstay of chemotherapy regimens in clinic. Nevertheless, the efficacy of platinum drugs is badly affected by serious systemic toxicities and drug resistance, and the pharmacokinetics of most platinum drugs is largely unknown. In recent years, a keen interest in functionalizing platinum complexes with bioactive molecules, targeting groups, photosensitizers, fluorophores, or nanomaterials has been sparked among chemical and biomedical researchers. The motivation for functionalization comes from some of the following demands: to improve the tumor selectivity or minimize the systemic toxicity of the drugs, to enhance the cellular accumulation of the drugs, to overcome the tumor resistance to the drugs, to visualize the drug molecules in vitro or in vivo, to achieve a synergistic anticancer effect between different therapeutic modalities, or to add extra functionality to the drugs. In this Account, we present different strategies being used for functionalizing platinum complexes, including conjugation with bisphosphonates, peptides, receptor-specific ligands, polymers, nanoparticles, magnetic resonance imaging contrast agents, metal chelators, or photosensitizers. Among them, bisphosphonates, peptides, and receptor-specific ligands are used for actively targeted drug delivery, polymers and nanoparticles are for passively targeted drug delivery, magnetic resonance imaging contrast agents are for theranostic purposes, metal chelators are for the treatment or prevention of Alzheimer's disease (AD), and photosensitizers are for photodynamic therapy of cancers. The rationales behind these designs are explained and justified at the molecular or cellular level, associating with the requirements for diagnosis, therapy, and visualization of biological processes. To illustrate the wide range of opportunities and challenges that are emerging in this realm, representative examples of targeted drug delivery systems, anticancer conjugates

  15. Methylation of platinum by methylcobalamin

    SciTech Connect

    Taylor, R.T.; Hanna, M.L.

    1984-01-01

    Incubation of micromolar levels of potassium hexachloroplatinate (K/sub 2/PtCl/sub 6/) and methylcobalamin (MeB-12) results in the complete conversion of MeB-12 to aquocobalamin (aquoB-12). Demethylation is optimal at approximately pH 2.0 and is accelerated by the addition of potassium tetrachloroplatinate (K/sub 2/PtCl/sub 4/). The reaction is stoichiometric between MeB-12 and the K/sub 2/PtCl/sub 6/ added (1:1). Isosbestic points at 492, 367, and 335 nm during the course of the reaction indicate that MeB-12 is demethylated to aquoB-12 with no accumulation of corrinoid intermediates. Higher alkylcobalamins and methylcobinamide react at much slower rates compared with MeB-12. Incubation of 40..mu..M K/sub 2/ PtCl/sub 6/ with either 40..mu..M (Me-/sup 14/C)MeB-12 or (Me-/sup 3/H)MeB-12 followed by lyophilization converts 70% of the label to a stable form that is associated with platinum upon subsequent paper chromatography and electrophoresis. There is no preferential loss of /sup 3/H relative to /sup 14/C in the reaction product. Difference spectra indicated that the platinum reaction product had an absorption maximum at 260 nm. When 50 ..mu..moles each of (Me-/sup 14/C)MeB-12 and K/sub 2/PtCl/sub 6/ were reacted and subjected to Sephadex G-15 chromatography, the /sup 14/C label eluted with 260 nm of absorbing material. Further chromatography on Sephadex G-15 and CM-cellulose yielded a labeled ultraviolet-absorbing product with a /sup 14/C/Pt ratio of 1.2. The overall recovery was 36 to 42% on the basis of the /sup 14/C. The /sup 14/C-Pt product has absorption maximums at 260 nm and 208 nm, with a minimum at 240 nm (A/sub 240/ nm/A/sub 260/ nm = 0.5). Proton-nuclear magnetic resonance (NMR) spectroscopy confirmed the presence of an H-C-Pt covalent bonding pattern (J for /sup 1/H, /sup 195/Pt = 78.2 Hz; tau for /sup 194/Pt-Me + /sup 196/Pt-Me = 6.956).

  16. Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor.

    PubMed

    Wu, Jingjing; Zhang, Mingzhi; Liu, Delong

    2016-03-09

    More and more targeted agents become available for B cell malignancies with increasing precision and potency. The first-in-class Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. More selective BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, CC-292) are being explored. Acalabrutinib (ACP-196) is a novel irreversible second-generation BTK inhibitor that was shown to be more potent and selective than ibrutinib. This review summarized the preclinical research and clinical data of acalabrutinib.

  17. 32 CFR 196.230 - Transition plans.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Transition plans. 196.230 Section 196.230... FINANCIAL ASSISTANCE Coverage § 196.230 Transition plans. (a) Submission of plans. An institution to which... a single transition plan applicable to all such units, or a separate transition plan applicable...

  18. 22 CFR 196.4 - Administering office.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Administering office. 196.4 Section 196.4 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION THOMAS R. PICKERING FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.4 Administering office. The Department of State...

  19. 32 CFR 196.605 - Enforcement procedures.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Enforcement procedures. 196.605 Section 196.605 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Procedures § 196.605...

  20. 32 CFR 196.605 - Enforcement procedures.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Enforcement procedures. 196.605 Section 196.605 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Procedures § 196.605...

  1. 32 CFR 196.605 - Enforcement procedures.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Enforcement procedures. 196.605 Section 196.605 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Procedures § 196.605...

  2. 32 CFR 196.605 - Enforcement procedures.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Enforcement procedures. 196.605 Section 196.605 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Procedures § 196.605...

  3. 32 CFR 196.605 - Enforcement procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Enforcement procedures. 196.605 Section 196.605 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Procedures § 196.605...

  4. 32 CFR 196.450 - Athletics.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Athletics. 196.450 Section 196.450 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.450 Athletics. (a... interscholastic, intercollegiate, club, or intramural athletics offered by a recipient, and no recipient shall...

  5. 32 CFR 196.450 - Athletics.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Athletics. 196.450 Section 196.450 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.450 Athletics. (a... interscholastic, intercollegiate, club, or intramural athletics offered by a recipient, and no recipient shall...

  6. 32 CFR 196.450 - Athletics.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Athletics. 196.450 Section 196.450 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.450 Athletics. (a... interscholastic, intercollegiate, club, or intramural athletics offered by a recipient, and no recipient shall...

  7. 46 CFR 196.34-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 196.34-1 Section 196.34-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-1 Application. (a) Provisions of this subpart shall apply to all vessels....

  8. 46 CFR 196.34-10 - Use.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Use. 196.34-10 Section 196.34-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-10 Use. (a) Approved buoyant work vests are considered to be items of safety apparel and may be...

  9. 46 CFR 196.53-1 - Officers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Officers. 196.53-1 Section 196.53-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Exhibition of Credential § 196.53-1 Officers. All officers on a vessel must have their licenses or officer endorsements...

  10. 46 CFR 196.43-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 196.43-1 Section 196.43-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Placard of Lifesaving Signals § 196.43-1 Application. The provisions of this subpart apply to all vessels on an...

  11. 46 CFR 196.12-1 - Posting.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Posting. 196.12-1 Section 196.12-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Stability Letter § 196.12-1 Posting. If a stability letter is issued in accordance with the requirements in § 170.120 of...

  12. 46 CFR 196.35-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 196.35-1 Section 196.35-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Logbook Entries § 196.35-1 Application. (a) Except as specifically noted, the provisions of this subpart shall...

  13. 46 CFR 196.01-1 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false General. 196.01-1 Section 196.01-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Application § 196.01-1 General. (a) The provisions of this part shall apply to all vessels except as specifically noted in this...

  14. 46 CFR 196.37-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 196.37-1 Section 196.37-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-1 Application. (a) The provisions of this subpart...

  15. 46 CFR 196.40-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 196.40-1 Section 196.40-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-1 Application. (a) The provisions of this subpart shall apply to all vessels except as...

  16. 46 CFR 196.15-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Application. 196.15-1 Section 196.15-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-1 Application. (a) The provisions of this subpart shall apply to all...

  17. 46 CFR 196.15-5 - Drafts.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Drafts. 196.15-5 Section 196.15-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-5 Drafts. (a) The master of every vessel on an ocean, coastwise, or Great Lakes voyage...

  18. 46 CFR 196.43-5 - Availability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Availability. 196.43-5 Section 196.43-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Placard of Lifesaving Signals § 196.43-5 Availability. On all vessels to which this subpart applies there must be...

  19. 32 CFR 196.230 - Transition plans.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Transition plans. 196.230 Section 196.230... FINANCIAL ASSISTANCE Coverage § 196.230 Transition plans. (a) Submission of plans. An institution to which... a single transition plan applicable to all such units, or a separate transition plan applicable...

  20. 32 CFR 196.230 - Transition plans.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Transition plans. 196.230 Section 196.230... FINANCIAL ASSISTANCE Coverage § 196.230 Transition plans. (a) Submission of plans. An institution to which... a single transition plan applicable to all such units, or a separate transition plan applicable...

  1. 21 CFR 211.196 - Distribution records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Distribution records. 211.196 Section 211.196 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Records and Reports § 211.196...

  2. 21 CFR 211.196 - Distribution records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Distribution records. 211.196 Section 211.196 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Records and Reports § 211.196...

  3. 27 CFR 24.196 - Formula required.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Formula required. 24.196 Section 24.196 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS WINE Production of Special Natural Wine § 24.196 Formula required....

  4. 46 CFR 196.53-1 - Officers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Officers. 196.53-1 Section 196.53-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Exhibition of Credential § 196.53-1 Officers. All officers on a vessel must have their licenses or officer...

  5. 46 CFR 196.12-1 - Posting.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Posting. 196.12-1 Section 196.12-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Stability Letter § 196.12-1 Posting. If a stability letter is issued in accordance with the requirements in § 170.120...

  6. 46 CFR 196.35-1 - Application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Application. 196.35-1 Section 196.35-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Logbook Entries § 196.35-1 Application. (a) Except as specifically noted, the provisions of this subpart...

  7. 46 CFR 196.01-1 - General.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false General. 196.01-1 Section 196.01-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Application § 196.01-1 General. (a) The provisions of this part shall apply to all vessels except as specifically noted in...

  8. 46 CFR 196.34-1 - Application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Application. 196.34-1 Section 196.34-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-1 Application. (a) Provisions of this subpart shall apply to all vessels....

  9. 46 CFR 196.34-10 - Use.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Use. 196.34-10 Section 196.34-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-10 Use. (a) Approved buoyant work vests are considered to be items of safety apparel and may be...

  10. 46 CFR 196.40-1 - Application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Application. 196.40-1 Section 196.40-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-1 Application. (a) The provisions of this subpart shall apply to all vessels except...

  11. 32 CFR 196.405 - Housing.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Housing. 196.405 Section 196.405 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.405 Housing. (a... different fees or requirements, or offer different services or benefits related to housing, except...

  12. 32 CFR 196.405 - Housing.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Housing. 196.405 Section 196.405 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.405 Housing. (a... different fees or requirements, or offer different services or benefits related to housing, except...

  13. 32 CFR 196.405 - Housing.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Housing. 196.405 Section 196.405 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.405 Housing. (a... different fees or requirements, or offer different services or benefits related to housing, except...

  14. 32 CFR 196.405 - Housing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Housing. 196.405 Section 196.405 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.405 Housing. (a... different fees or requirements, or offer different services or benefits related to housing, except...

  15. 32 CFR 196.405 - Housing.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Housing. 196.405 Section 196.405 National... Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.405 Housing. (a... different fees or requirements, or offer different services or benefits related to housing, except...

  16. 46 CFR 196.34-10 - Use.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Use. 196.34-10 Section 196.34-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-10 Use. (a) Approved buoyant work vests are considered to be items of safety apparel and may be...

  17. 32 CFR 196.430 - Financial assistance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Financial assistance. 196.430 Section 196.430... FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.430 Financial assistance. (a) General. Except as provided in paragraphs (b) and (c) of this...

  18. 32 CFR 196.430 - Financial assistance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Financial assistance. 196.430 Section 196.430... FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.430 Financial assistance. (a) General. Except as provided in paragraphs (b) and (c) of this...

  19. 32 CFR 196.430 - Financial assistance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Financial assistance. 196.430 Section 196.430... FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.430 Financial assistance. (a) General. Except as provided in paragraphs (b) and (c) of this...

  20. 32 CFR 196.430 - Financial assistance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Financial assistance. 196.430 Section 196.430... FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Education Programs or Activities Prohibited § 196.430 Financial assistance. (a) General. Except as provided in paragraphs (b) and (c) of this...

  1. 46 CFR 196.15-10 - Sanitation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Sanitation. 196.15-10 Section 196.15-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-10 Sanitation. (a) It shall be the duty of the master and chief...

  2. 46 CFR 196.15-10 - Sanitation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Sanitation. 196.15-10 Section 196.15-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-10 Sanitation. (a) It shall be the duty of the master and chief...

  3. 46 CFR 196.15-10 - Sanitation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Sanitation. 196.15-10 Section 196.15-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-10 Sanitation. (a) It shall be the duty of the master and chief...

  4. 46 CFR 196.15-10 - Sanitation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Sanitation. 196.15-10 Section 196.15-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-10 Sanitation. (a) It shall be the duty of the master and chief...

  5. 46 CFR 196.15-10 - Sanitation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Sanitation. 196.15-10 Section 196.15-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-10 Sanitation. (a) It shall be the duty of the master and chief...

  6. Biomineralization of platinum by microorganisms

    NASA Astrophysics Data System (ADS)

    Pavlova, L. M.; Radomskaya, V. I.; Shumilova, L. P.; Ionov, A. M.; Sorokin, P.

    2017-04-01

    The mechanism of platinum biomineralization by microscopic fungi is displayed based on data of electron microscopy, infrared and X-ray photoelectronic spectroscopy. It was suggested the platinum sorption process by microscopic fungi has some stages. The initial interaction is carried out by the mechanisms of physical and chemical sorption. Hereafter the reduction process of adsorbed platinum ions up to zero state is performed, probably, for account of organic compounds, which are produced by fungi biomass as metabolism result, and the process terminates by nulvalent particles aggregating up to nanosize forms. Obtained data on the platinum biomineralization extends the concept concerning the character of forming platinum nanoparticles in carbonous paleobasin.

  7. Cubic colloidal platinum nanoparticles

    SciTech Connect

    Ahmadi, T.S.; Wang, Z.L.; Henglein, A.; El-Sayed, M.A.

    1996-06-01

    Cubic platinum nanoparticles (4-18 nm) have been synthesized for the first time in solution by the controlled reduction of K{sub 2}PtCl{sub 4} with hydrogen gas in the presence of sodium polyacrylate as a capping material. The nanoparticles are found to have fcc structures, similar to the bulk metal with (100) facets.

  8. Growth of platinum nanocrystals

    SciTech Connect

    2009-01-01

    Movie showing the growth of platinum nanocrystals in a liquid cell observed in situ using the JEOL 3010 TEM at the National Center for Electron Microscopy. This is the first ever-real time movie showing nucleation and growth by monomer attachment or by smaller nanocrystals coalescing to form larger nanocrystals. All the nanocrystals end up being roughly the same shape and size. http://newscenter.lbl.gov/feature-stories/2009/08/04/growth-spurts/

  9. Nuclear Data Sheets for A = 196

    SciTech Connect

    Huang Xiaolong

    2007-06-15

    The 1998 version of nuclear data sheets for A = 196 has been revised and updated on the basis of the experimental results from various decay and reaction studies before January 2006. The experimental data for all known nuclei of A = 196 (Os,Ir,Pt,Au,Hg, Tl,Pb,Bi,Po,At,Rn) have been reevaluated. The experimental methods, references,J{pi} arguments,and necessary comments are given in the text. Summary band structure drawings and level schemes from both radioactive decay and reaction studies are presented. Also of special interest are the new identification of superdeformed bands in {sup 196}Pb and {sup 196}Bi.

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

    PubMed

    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).

  11. Liposomes, a promising strategy for clinical application of platinum derivatives.

    PubMed

    Zalba, Sara; Garrido, María J

    2013-06-01

    Liposomes represent a versatile system for drug delivery in various pathologies. Platinum derivatives have been demonstrated to have therapeutic efficacy against several solid tumors. But their use is limited due to their side effects. Since liposomal formulations are known to reduce the toxicity of some conventional chemotherapeutic drugs, the encapsulation of platinum derivatives in these systems may be useful in reducing toxicity and maintaining an adequate therapeutic response. This review describes the strategies applied to platinum derivatives in order to improve their therapeutic activity, while reducing the incidence of side effects. It also reviews the results found in the literature for the different platinum-drugs liposomal formulations and their current status. The design of liposomes to achieve effectiveness in antitumor treatment is a goal for platinum derivatives. Liposomes can change the pharmacokinetic parameters of these encapsulated drugs, reducing their side effects. However, few liposomal formulations have demonstrated a significant advantage in therapeutic terms. Lipoplatin, a cisplatin formulation in Phase III, combines a reduction in the toxicity associated with an antitumor activity similar to the free drug. Thermosensitive or targeted liposomes for tumor therapy are also included in this review. Few articles about this strategy applied to platinum drugs can be found in the literature.

  12. 32 CFR 196.540 - Advertising.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Advertising. 196.540 Section 196.540 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... Advertising. A recipient shall not in any advertising related to employment indicate preference,...

  13. 32 CFR 196.510 - Recruitment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Recruitment. 196.510 Section 196.510 National... Recruitment. (a) Nondiscriminatory recruitment and hiring. A recipient shall not discriminate on the basis of sex in the recruitment and hiring of employees. Where a recipient has been found to be presently...

  14. 32 CFR 196.540 - Advertising.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Advertising. 196.540 Section 196.540 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... Advertising. A recipient shall not in any advertising related to employment indicate preference,...

  15. 32 CFR 196.540 - Advertising.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Advertising. 196.540 Section 196.540 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... Advertising. A recipient shall not in any advertising related to employment indicate preference,...

  16. 32 CFR 196.540 - Advertising.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Advertising. 196.540 Section 196.540 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... Advertising. A recipient shall not in any advertising related to employment indicate preference,...

  17. 32 CFR 196.540 - Advertising.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Advertising. 196.540 Section 196.540 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS... Advertising. A recipient shall not in any advertising related to employment indicate preference,...

  18. 32 CFR 196.220 - Admissions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... higher education, and public institutions of undergraduate higher education. (e) Public institutions of undergraduate higher education. §§ 196.300 through 196.310 do not apply to any public institution of undergraduate higher education that traditionally and continually from its establishment has had a policy...

  19. 32 CFR 196.220 - Admissions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... higher education, and public institutions of undergraduate higher education. (e) Public institutions of undergraduate higher education. §§ 196.300 through 196.310 do not apply to any public institution of undergraduate higher education that traditionally and continually from its establishment has had a policy...

  20. 32 CFR 196.220 - Admissions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... higher education, and public institutions of undergraduate higher education. (e) Public institutions of undergraduate higher education. §§ 196.300 through 196.310 do not apply to any public institution of undergraduate higher education that traditionally and continually from its establishment has had a policy...

  1. 32 CFR 196.220 - Admissions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... higher education, and public institutions of undergraduate higher education. (e) Public institutions of undergraduate higher education. §§ 196.300 through 196.310 do not apply to any public institution of undergraduate higher education that traditionally and continually from its establishment has had a policy...

  2. 32 CFR 196.220 - Admissions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... higher education, and public institutions of undergraduate higher education. (e) Public institutions of undergraduate higher education. §§ 196.300 through 196.310 do not apply to any public institution of undergraduate higher education that traditionally and continually from its establishment has had a policy...

  3. 32 CFR 196.410 - Comparable facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Comparable facilities. 196.410 Section 196.410....410 Comparable facilities. A recipient may provide separate toilet, locker room, and shower facilities on the basis of sex, but such facilities provided for students of one sex shall be comparable to...

  4. 32 CFR 196.515 - Compensation.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Compensation. 196.515 Section 196.515 National... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  5. 32 CFR 196.515 - Compensation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Compensation. 196.515 Section 196.515 National... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  6. 32 CFR 196.515 - Compensation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Compensation. 196.515 Section 196.515 National... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  7. 32 CFR 196.515 - Compensation.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Compensation. 196.515 Section 196.515 National... Compensation. A recipient shall not make or enforce any policy or practice that, on the basis of sex: (a) Makes distinctions in rates of pay or other compensation; (b) Results in the payment of wages to employees of one...

  8. 32 CFR 196.500 - Employment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... denied the benefits of, or be subjected to discrimination in employment, or recruitment, consideration... effect of subjecting employees or students to discrimination prohibited by §§ 196.500 through 196.550... the effect of discriminating on the basis of sex in violation of these Title IX regulations....

  9. A brief review of the management of platinum-resistant-platinum-refractory ovarian cancer.

    PubMed

    Oronsky, Bryan; Ray, Carolyn M; Spira, Alexander I; Trepel, Jane B; Carter, Corey A; Cottrill, Hope M

    2017-06-01

    Ovarian cancer, which ranks fifth in cancer deaths among women, is the most lethal gynecologic malignancy. Epithelial ovarian cancer (EOC) is the most common histologic type, with the 5-year survival for all stages estimated at 45.6%. This rate increases to more than 70% in the minority of patients who are diagnosed at an early stage, but declines to 35% in the vast majority of patients diagnosed at advanced stage. Recurrent EOC is incurable. Platinum sensitivity (or lack thereof) is a major determinant of prognosis. The current standard treatment is primary surgery followed by platinum-based chemotherapy. In recurrent platinum-resistant/platinum-refractory EOC, sequential single-agent salvage chemotherapy is superior to multiagent chemotherapy. Multiagent regimens increase toxicity without clear benefit; however, no preferred sequence of single agents is recommended. The impact of targeted therapies and immunotherapies on progression-free survival and overall survival, which remains dismal, is under active investigation. Currently, clinical trials offer the best hope for the development of a new treatment paradigm in this recalcitrant disease.

  10. Platinum nitride with fluorite structure

    SciTech Connect

    Yu, Rong; Zhang, Xiao-Feng

    2005-01-31

    The mechanical stability of platinum nitride has been studied using first-principles calculations. By calculating the single-crystal elastic constants, we show that platinum nitride can be stabilized in the fluorite structure, in which the nitrogen atoms occupy all the tetrahedral interstitial sites of the metal lattice. The stability is attributed to the pseudogap effect from analysis of the electronic structure.

  11. Recent Approaches to Platinum(IV) Prodrugs: A Variety of Strategies for Enhanced Delivery and Efficacy.

    PubMed

    Najjar, Anas; Rajabi, Naeema; Karaman, Rafik

    2017-01-01

    Intensive efforts have been implemented to improve the efficacy of platinum complexes especially with emerging cisplatin resistance and elevated cancer deaths. Platinum(IV) agents show better pharmacokinetics and decreased side effects compared to Platinum(II) agents. This review aims to summarize and categorize the strategies being employed to improve the efficacy of Platinum-based anticancer agents in recent years. Nanoparticles and nanoplatforms offer a vast variety of strategies in targeting specific tumor types and delivering one or two lethal drugs simultaneously. Theranostic agents are being developed to achieve enhanced imaging and provide further insight into the activity of platinum containing chemotherapy. Moreover, photoactivation of Pt(IV) prodrugs specifically at the tumor site is gaining attention due to a controlled activity. A platinum agent formulated as large multi-activity complex is the most common strategy being employed. Platinum(IV) agents offer great potential in targeting, increasing efficacy, and decreasing toxicity of Platinum-based anticancer agents. The strategies being employed are aiming to increase specificity and targeting as well as provide more potent agents. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Development of Platinum(iv) Complexes as Anticancer Prodrugs: the Story so Far

    NASA Astrophysics Data System (ADS)

    Wong, Daniel Yuan Qiang; Ang, Wee Han

    2012-06-01

    The serendipitous discovery of the antitumor properties of cisplatin by Barnett Rosenberg some forty years ago brought about a paradigm shift in the field of medicinal chemistry and challenged conventional thinking regarding the role of potentially toxic heavy metals in drugs. Platinum(II)-based anticancer drugs have since become some of the most effective and widely-used drugs in a clinician's arsenal and have saved countless lives. However, they are limited by high toxicity, severe side-effects and the incidence of drug resistance. In recent years, attention has shifted to stable platinum(IV) complexes as anticancer prodrugs. By exploiting the unique chemical and structural attributes of their scaffolds, these platinum(IV) prodrugs offer new strategies of targeting and killing cancer cells. This review summarizes the development of anticancer platinum(IV) prodrugs to date and some of the exciting strategies that utilise the platinum(IV) construct as targeted chemotherapeutic agents against cancer.

  13. Birinapant sensitizes platinum-resistant carcinomas with high levels of cIAP to carboplatin therapy

    PubMed Central

    La, V.; Fujikawa, R.; Janzen, D. M.; Nunez, M.; Bainvoll, L.; Hwang, L.; Faull, K.; Lawson, G.; Memarzadeh, S.

    2017-01-01

    Platinum drugs are the frontline therapy in many carcinomas, including high-grade serous ovarian cancers. Clinically, high-grade serous carcinomas have an apparent complete response to carboplatin, but tumors invariably recur and response to platinum drugs diminishes over time. Standard of care prohibits re-administration of platinum drugs to these patients who are labeled as having platinum-resistant disease. In this stage patients are treated with non-platinum agents and outcomes are often poor. In vivo and in vitro data presented here demonstrate that this clinical dogma should be challenged. Platinum drugs can be an effective therapy even for platinum-resistant carcinomas as long as they are combined with an agent that specifically targets mechanisms of platinum resistance exploited by the therapy-resistant tumor subpopulations. High levels of cellular inhibitor of apoptosis proteins cIAP1 and 2 (cIAP) were detected in up to 50% of high-grade serous and non-high-grade serous platinum-resistant carcinomas. cIAP proteins can induce platinum resistance and they are effectively degraded with the drug birinapant. In platinum-resistant tumors with ≥22.4 ng of cIAP per 20 μg of tumor lysate, the combination of birinapant with carboplatin was effective in eliminating the cancer. Our findings provide a new personalized therapeutic option for patients with platinum-resistant carcinomas. The efficacy of birinapant in combination with carboplatin should be tested in high-grade serous carcinoma patients in a clinical trial. PMID:28804784

  14. Platinum in phosphate laser glasses

    NASA Astrophysics Data System (ADS)

    Click, Carol Ann

    The platinum concentration in phosphate laser glasses has been characterized as a function of composition, melting time and temperature. The highest measured ionic platinum concentration is 2042 ppmw in a potassium-alumino-metaphosphate glass after 24 hours of melting at 900°C. The maximum platinum concentration in a given composition decreases with increasing temperature. The time, temperature and composition dependent platinum concentration in the melt depends on the relative rates of the platinum dissolution from the crucible wall into and platinum oxide volatilization out of the glass melt. As such, the platinum concentration in the melt can be seen to decrease with increasing time under some conditions. The local environment of the ionic platinum in these glasses has been investigated using optical spectroscopy. The ionic platinum is incorporated as Pt4+ ions in a distorted octahedral symmetry. This platinum is characterized by optical absorption occurring at wavelengths less than 500nm (energy > 20,000 cm-1) due to d-d electronic transitions. The addition of chlorine to the system results in an electronic transition shift to greater wavelengths in barium free glasses, which indicates that the chlorine is coordinating to the platinum in the barium free glasses. The effect of platinum on the Nd3+ 4F 3/2 → 4I11/2 fluorescence decay rate in a commercial laser glass has been investigated, and the effect is negligible. However, the effects of hydroxyl concentration and Nd2O3 concentration on the fluorescence decay rate are substantial and have been investigated in potassium-magnesium-aluminometaphosphate glasses with Nd 2O3 contents ranging from 0.5 to 8.0 weight%. The hydroxyl concentration ranged from ˜3 to 43 cm-1 at 3.33 mum, corresponding to hydroxyl concentrations of ˜300 to 4300 ppm. The fluorescence quenching rate of the Nd3+ ions by hydroxyls increases linearly with Nd atomic concentration, and when extrapolated to zero Nd concentration, has a value

  15. Understanding platinum-induced ototoxicity.

    PubMed

    Langer, Thorsten; am Zehnhoff-Dinnesen, Antoinette; Radtke, Susanne; Meitert, Johannes; Zolk, Oliver

    2013-08-01

    Childhood cancer survival rates are now nearly 80% in more developed European countries because of improved therapies and better supportive care. Platinum chemotherapy drugs, such as cisplatin and carboplatin, are the cornerstone of many effective therapeutic protocols for childhood cancer. However, the antitumor efficacy of cisplatin and carboplatin comes at the cost of ototoxicity, which affects at least 60% of pediatric patients. Although ototoxicity is not life threatening, it can have debilitating effects on patients' quality of life. Recently, many initiatives have been launched with the ultimate goal of reducing cisplatin and high-dose carboplatin ototoxicity without compromising antitumor efficacy. This review addresses the incidence of platinum ototoxicity and its clinical presentation, time course, and early diagnostic evaluation. Genetic and non-genetic risk factors for platinum-associated ototoxicity, and their predictive value, are discussed. Recent developments in the prevention of platinum ototoxicity are also summarized. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Platinum availability for future automotive technologies.

    PubMed

    Alonso, Elisa; Field, Frank R; Kirchain, Randolph E

    2012-12-04

    Platinum is an excellent catalyst, can be used at high temperatures, and is stable in many aggressive chemical environments. Consequently, platinum is used in many current industrial applications, notably automotive catalytic converters, and prospective vehicle fuel cells are expected to rely upon it. Between 2005 and 2010, the automotive industry used approximately 40% of mined platinum. Future automotive industry growth and automotive sales shifts toward new technologies could significantly alter platinum demand. The potential risks for decreased platinum availability are evaluated, using an analysis of platinum market characteristics that describes platinum's geophysical constraints, institutional efficiency, and dynamic responsiveness. Results show that platinum demand for an automotive fleet that meets 450 ppm greenhouse gas stabilization goals would require within 10% of historical growth rates of platinum supply before 2025. However, such a fleet, due largely to sales growth in fuel cell vehicles, will more strongly constrain platinum supply in the 2050 time period. While current platinum reserves are sufficient to satisfy this increased demand, decreasing platinum ore grade and continued concentration of platinum supply in a single geographic area are availability risk factors to platinum end-users.

  17. HDAC4-regulated STAT1 activation mediates platinum resistance in ovarian cancer

    PubMed Central

    Stronach, Euan A; Alfraidi, Albandri; Rama, Nona; Datler, Christoph; Studd, Jamie; Agarwal, Roshan; Guney, Tankut G; Gourley, Charlie; Hennessy, Bryan T; Mills, Gordon B; Mai, Antonello; Brown, Robert; Dina, Roberto; Gabra, Hani

    2011-01-01

    Ovarian cancer frequently acquires resistance to platinum chemotherapy, representing a major challenge for improving patient survival. Recent work suggests resistant clones exist within a larger drug sensitive cell-population prior to chemotherapy, implying that resistance is selected for rather than generated by treatment. We sought to compare clinically-derived, intra-patient paired models of initial platinum response and subsequent resistant relapse to define molecular determinants of evolved resistance. Transcriptional analysis of a matched cell-line series from three patients with high-grade serous ovarian cancer before and after development of clinical platinum resistance (PEO1/PEO4/PEO6, PEA1/PEA2, PEO14/PEO23) identified 91 up- and 126 down-regulated genes common to acquired resistance. Significantly enhanced apoptotic response to platinum treatment in resistant cells was observed following knockdown of HDAC4, FOLR2, PIK3R1 or STAT1 (p<0.05). Interestingly, HDAC4 and STAT1 were found to physically interact. Acetyl-STAT1 was detected in platinum sensitive but not HDAC4 over-expressing platinum resistant cells from the same patient. In resistant cells, STAT1 phosphorylation/nuclear translocation was seen following platinum exposure, whereas silencing of HDAC4 increased acetyl-STAT1 levels, prevented platinum induced STAT1 activation and restored cisplatin sensitivity. Conversely, matched sensitive cells were refractory to STAT1 phosphorylation on platinum treatment. Analysis of 16 paired tumor biopsies taken before and after development of clinical platinum resistance showed significantly increased HDAC4 expression in resistant tumors (n=7/16[44%]; p=0.04). Therefore, clinical selection of HDAC4 overexpressing tumor cells upon exposure to chemotherapy promotes STAT1 deacetylation and cancer cell survival. Together, our findings identify HDAC4 as a novel, therapeutically tractable target to counter platinum resistance in ovarian cancer. PMID:21571862

  18. Fluorometric imaging methods for palladium and platinum and the use of palladium for imaging biomolecules.

    PubMed

    Tracey, Matthew P; Pham, Dianne; Koide, Kazunori

    2015-07-21

    Neither palladium nor platinum is an endogenous biological metal. Imaging palladium in biological samples, however, is becoming increasingly important because bioorthogonal organometallic chemistry involves palladium catalysis. In addition to being an imaging target, palladium has been used to fluorometrically image biomolecules. In these cases, palladium species are used as imaging-enabling reagents. This review article discusses these fluorometric methods. Platinum-based drugs are widely used as anticancer drugs, yet their mechanism of action remains largely unknown. We discuss fluorometric methods for imaging or quantifying platinum in cells or biofluids. These methods include the use of chemosensors to directly detect platinum, fluorescently tagging platinum-based drugs, and utilizing post-labeling to elucidate distribution and mode of action.

  19. miR-196b Is Epigenetically Silenced during the Premalignant Stage of Lung Carcinogenesis.

    PubMed

    Tellez, Carmen S; Juri, Daniel E; Do, Kieu; Picchi, Maria A; Wang, Teresa; Liu, Gang; Spira, Avrum; Belinsky, Steven A

    2016-08-15

    miRNA silencing by promoter hypermethylation may represent a mechanism by which lung cancer develops and progresses, but the miRNAs involved during malignant transformation are unknown. We previously established a model of premalignant lung cancer wherein we treated human bronchial epithelial cells (HBEC) with low doses of tobacco carcinogens. Here, we demonstrate that next-generation sequencing of carcinogen-transformed HBECs treated with the demethylating agent 5-aza-2'deoxycytidine revealed miR-196b and miR-34c-5p to be epigenetic targets. Bisulfite sequencing confirmed dense promoter hypermethylation indicative of silencing in multiple malignant cell lines and primary tumors. Chromatin immunoprecipitation studies further demonstrated an enrichment in repressive histone marks on the miR-196b promoter during HBEC transformation. Restoration of miR-196b expression by transfecting transformed HBECs with specific mimics led to cell-cycle arrest mediated in part through transcriptional regulation of the FOS oncogene, and miR-196b reexpression also significantly reduced the growth of tumor xenografts. Luciferase assays demonstrated that forced expression of miR-196b inhibited the FOS promoter and AP-1 reporter activity. Finally, a case-control study revealed that methylation of miR-196b in sputum was strongly associated with lung cancer (OR = 4.7, P < 0.001). Collectively, these studies highlight miR-196b as a tumor suppressor whose silencing early in lung carcinogenesis may provide a selective growth advantage to premalignant cells. Targeted delivery of miR-196b could therefore serve as a preventive or therapeutic strategy for the management of lung cancer. Cancer Res; 76(16); 4741-51. ©2016 AACR.

  20. Cross-reactivity of Halogenated Platinum Salts

    EPA Science Inventory

    Halogenated platinum (Pt) salts are well-known respiratory sensitizers associated with the development of asthma. People may be exposed to a variety of platinum compounds in different contexts (e.g. occupationally, automobile exhaust). Published reports suggest that sensitizati...

  1. Cross-reactivity of Halogenated Platinum Salts

    EPA Science Inventory

    Halogenated platinum (Pt) salts are well-known respiratory sensitizers associated with the development of asthma. People may be exposed to a variety of platinum compounds in different contexts (e.g. occupationally, automobile exhaust). Published reports suggest that sensitizati...

  2. Antimicrobial Properties of Diamondlike Carbon-Silver-Platinum Nanocomposite Thin Films

    SciTech Connect

    CHRISTOPHER, BERRY

    2005-03-07

    Silver and platinum were incorporated within diamondlike carbon (DLC) thin films using a multicomponent target pulsed laser deposition process. Transmission electron microscopy of the DLC-silver and DLC-platinum composite films reveals that the metals self-assemble into particulate nanocomposite structures. Nanoindentation testing has shown that diamondlike carbon-silver films exhibit hardness and Young's modulus values of approximately 37 GPa and 333 GPa, respectively. DLC-silver-platinum films exhibited antimicrobial properties against Staphylococcus bacteria. Diamondlike carbon-biofunctional metal nanocomposite films have a variety of potential medical and antimicrobial applications.

  3. Phosphorus adlayers on Platinum (110)

    NASA Astrophysics Data System (ADS)

    Heikkinen, Olli; Riihimäki, Ari; Sainio, Jani; Lahtinen, Jouko

    2017-10-01

    Platinum is a metal utilized in many applications. Its catalytic activity can be decreased due to chemical poisoning caused e.g. by phosphorus. To gain more understanding of its poisoning, we present a study of phosphorus adsorption on a platinum (110) single crystal surface. Using X-ray photoelectron spectroscopy, we have found that the adsorbate coverage saturates at around 3 monolayers. Annealing the phosphorus-covered platinum surface at 750 °C gives rise to three different ordered adlayer structures, with symmetries of 2 × 3, 11 × 4 and √{ 2} × 1 , from the lowest to the highest coverage, detected with low-energy electron diffraction. We have studied the sample topography with scanning tunnelling microscopy. We also present a tentative model for the observed structures and their evolution.

  4. Coating Carbon Fibers With Platinum

    NASA Technical Reports Server (NTRS)

    Effinger, Michael R.; Duncan, Peter; Coupland, Duncan; Rigali, Mark J.

    2007-01-01

    A process for coating carbon fibers with platinum has been developed. The process may also be adaptable to coating carbon fibers with other noble and refractory metals, including rhenium and iridium. The coated carbon fibers would be used as ingredients of matrix/fiber composite materials that would resist oxidation at high temperatures. The metal coats would contribute to oxidation resistance by keeping atmospheric oxygen away from fibers when cracks form in the matrices. Other processes that have been used to coat carbon fibers with metals have significant disadvantages: Metal-vapor deposition processes yield coats that are nonuniform along both the lengths and the circumferences of the fibers. The electrical resistivities of carbon fibers are too high to be compatible with electrolytic processes. Metal/organic vapor deposition entails the use of expensive starting materials, it may be necessary to use a furnace, and the starting materials and/or materials generated in the process may be hazardous. The present process does not have these disadvantages. It yields uniform, nonporous coats and is relatively inexpensive. The process can be summarized as one of pretreatment followed by electroless deposition. The process consists of the following steps: The surfaces of the fiber are activated by deposition of palladium crystallites from a solution. The surface-activated fibers are immersed in a solution that contains platinum. A reducing agent is used to supply electrons to effect a chemical reduction in situ. The chemical reduction displaces the platinum from the solution. The displaced platinum becomes deposited on the fibers. Each platinum atom that has been deposited acts as a catalytic site for the deposition of another platinum atom. Hence, the deposition process can also be characterized as autocatalytic. The thickness of the deposited metal can be tailored via the duration of immersion and the chemical activity of the solution.

  5. 32 CFR 196.500 - Employment.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ..., leave for persons of either sex to care for children or dependents, or any other leave; (7) Fringe... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 196.500...

  6. 32 CFR 196.500 - Employment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., leave for persons of either sex to care for children or dependents, or any other leave; (7) Fringe... NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Discrimination on the Basis of Sex in Employment in Education Programs or Activities Prohibited § 196.500...

  7. Method for forming porous platinum films

    DOEpatents

    Maya, Leon

    2000-01-01

    A method for forming a platinum film includes providing a substrate, sputtering a crystalline platinum oxide layer over at least a portion of the substrate, and reducing the crystalline platinum oxide layer to form the platinum film. A device includes a non-conductive substrate and a platinum layer having a density of between about 2 and 5 g/cm.sup.3 formed over at least a portion of the non-conductive substrate. The platinum films produced in accordance with the present invention provide porous films suitable for use as electrodes, yet require few processing steps. Thus, such films are less costly. Such films may be formed on both conductive and non-conductive substrates. While the invention has been illustrated with platinum, other metals, such as noble metals, that form a low density oxide when reactively sputtered may also be used.

  8. Nanocarriers for delivery of platinum anticancer drugs☆

    PubMed Central

    Oberoi, Hardeep S.; Nukolova, Natalia V.; Kabanov, Alexander V.; Bronich, Tatiana K.

    2014-01-01

    Platinum based anticancer drugs have revolutionized cancer chemotherapy, and continue to be in widespread clinical use especially for management of tumors of the ovary, testes, and the head and neck. However, several dose limiting toxicities associated with platinum drug use, partial anti-tumor response in most patients, development of drug resistance, tumor relapse, and many other challenges have severely limited the patient quality of life. These limitations have motivated an extensive research effort towards development of new strategies for improving platinum therapy. Nanocarrier-based delivery of platinum compounds is one such area of intense research effort beginning to provide encouraging preclinical and clinical results and may allow the development of the next generation of platinum chemotherapy. This review highlights current understanding on the pharmacology and limitations of platinum compounds in clinical use, and provides a comprehensive analysis of various platinum–polymer complexes, micelles, dendrimers, liposomes and other nanoparticles currently under investigation for delivery of platinum drugs. PMID:24113520

  9. [Formylation of porphyrin platinum complexes].

    PubMed

    Rumiantseva, V D; Konovalenko, L I; Nagaeva, E A; Mironov, A F

    2005-01-01

    The formylation reaction of platinum complexes of beta-unsubstituted porphyrins was studied. The interaction of deuteroporphyrin IX derivatives with the Vilsmeyer reagent led to the selective formylation of their macrocycles in the beta position. The resulting formyl derivatives of the porphyrins are of interest for fluorescent immunoassay.

  10. Production of platinum radioisotopes at Brookhaven Linac Isotope Producer (BLIP)

    NASA Astrophysics Data System (ADS)

    Smith, Suzanne V.; McCutchan, Elizabeth; Gürdal, Gülhan; Lister, Christopher; Muench, Lisa; Nino, Michael; Sonzogni, Alexandro; Herman, Michal; Nobre, Gustavo; Cullen, Chris; Chillery, Thomas; Chowdury, Partha; Harding, Robert

    2017-09-01

    The accelerator production of platinum isotopes was investigated at the Brookhaven Linac Isotope Producer (BLIP). In this study high purity natural platinum foils were irradiated at 53.2, 65.7, 105.2, 151.9, 162.9 and 173.3.MeV. The irradiated foils were digested in aqua regia and then converted to their hydrochloride salt with concentrated hydrochloric acid before analyzing by gamma spectrometry periodically for at least 10 days post end of bombardment. A wide range of platinum (Pt), gold (Au) and iridium (Ir) isotopes were identified. Effective cross sections at BLIP for Pt-188, Pt-189, Pt-191 and Pt-195m were compared to literature and theoretical cross sections determined using Empire-3.2. The majority of the effective cross sections (<70 MeV) confirm those reported in the literature. While the absolute values of the theoretical cross sections were up to a factor of 3 lower, Empire 3.2 modeled thresholds and maxima correlated well with experimental values. Preliminary evaluation into a rapid separation of Pt isotopes from high levels of Ir and Au isotopes proved to be a promising approach for large scale production. In conclusion, this study demonstrated that with the use of isotopically enriched target material accelerator production of selected platinum isotopes is feasible over a wide proton energy range.

  11. Internal correction of hafnium oxide spectral interferences and mass bias in the determination of platinum in environmental samples using isotope dilution analysis.

    PubMed

    Rodríguez-Castrillón, José Angel; Moldovan, Mariella; García Alonso, J Ignacio

    2009-05-01

    A method has been developed for the accurate determination of platinum by isotope dilution analysis, using enriched (194)Pt, in environmental samples containing comparatively high levels of hafnium without any chemical separation. The method is based on the computation of the contribution of hafnium oxide as an independent factor in the observed isotope pattern of platinum in the spiked sample. Under these conditions, the ratio of molar fractions between natural abundance and isotopically enriched platinum was independent of the amount of hafnium present in the sample. Additionally, mass bias was corrected by an internal procedure in which the regression variance was minimised. This was possible as the mass bias factor for hafnium oxide was very close to that of platinum. The final procedure required the measurement of three platinum isotope ratios (192/194, 195/194 and 196/194) to calculate the concentration of platinum in the sample. The methodology has been validated using the reference material "BCR-723 road dust" and has been applied to different environmental matrices (road dust, air particles, bulk wet deposition and epiphytic lichens) collected in the Aspe Valley (Pyrenees Mountains). A full uncertainty budget, using Kragten's spreadsheet method, showed that the total uncertainty was limited only by the uncertainty in the measured isotope ratios and not by the uncertainties of the isotopic composition of platinum and hafnium.

  12. Platinum dendritic nanoparticles with magnetic behavior

    SciTech Connect

    Li, Wenxian; Sun, Ziqi; Nevirkovets, Ivan P.; Dou, Shi-Xue; Tian, Dongliang

    2014-07-21

    Magnetic nanoparticles have attracted increasing attention for biomedical applications in magnetic resonance imaging, high frequency magnetic field hyperthermia therapies, and magnetic-field-gradient-targeted drug delivery. In this study, three-dimensional (3D) platinum nanostructures with large surface area that features magnetic behavior have been demonstrated. The well-developed 3D nanodendrites consist of plentiful interconnected nano-arms ∼4 nm in size. The magnetic behavior of the 3D dendritic Pt nanoparticles is contributed by the localization of surface electrons due to strongly bonded oxygen/Pluronic F127 and the local magnetic moment induced by oxygen vacancies on the neighboring Pt and O atoms. The magnetization of the nanoparticles exhibits a mixed paramagnetic and ferromagnetic state, originating from the core and surface, respectively. The 3D nanodendrite structure is suitable for surface modification and high amounts of drug loading if the transition temperature was enhanced to room temperature properly.

  13. 46 CFR 196.37-8 - Carbon dioxide warning signs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Carbon dioxide warning signs. 196.37-8 Section 196.37-8... Markings for Fire and Emergency Equipment, etc. § 196.37-8 Carbon dioxide warning signs. Each entrance to a space storing carbon dioxide cylinders, a space protected by carbon dioxide systems, or any space into...

  14. 46 CFR 196.37-8 - Carbon dioxide warning signs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Carbon dioxide warning signs. 196.37-8 Section 196.37-8... Markings for Fire and Emergency Equipment, etc. § 196.37-8 Carbon dioxide warning signs. Each entrance to a space storing carbon dioxide cylinders, a space protected by carbon dioxide systems, or any space into...

  15. 46 CFR 196.37-9 - Carbon dioxide alarm.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Carbon dioxide alarm. 196.37-9 Section 196.37-9 Shipping... Markings for Fire and Emergency Equipment, etc. § 196.37-9 Carbon dioxide alarm. (a) All carbon dioxide alarms shall be conspicuously identified: “WHEN ALARM SOUNDS—VACATE AT ONCE. CARBON DIOXIDE BEING...

  16. 46 CFR 196.37-9 - Carbon dioxide alarm.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Carbon dioxide alarm. 196.37-9 Section 196.37-9 Shipping... Markings for Fire and Emergency Equipment, etc. § 196.37-9 Carbon dioxide alarm. (a) All carbon dioxide alarms shall be conspicuously identified: “WHEN ALARM SOUNDS—VACATE AT ONCE. CARBON DIOXIDE BEING...

  17. 46 CFR 196.37-8 - Carbon dioxide warning signs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Carbon dioxide warning signs. 196.37-8 Section 196.37-8... Markings for Fire and Emergency Equipment, etc. § 196.37-8 Carbon dioxide warning signs. Each entrance to a space storing carbon dioxide cylinders, a space protected by carbon dioxide systems, or any space into...

  18. 46 CFR 196.25-1 - Improper use prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Improper use prohibited. 196.25-1 Section 196.25-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Searchlights § 196.25-1 Improper use prohibited. (a) No person shall flash or cause to be flashed the rays of...

  19. 46 CFR 196.25-1 - Improper use prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Improper use prohibited. 196.25-1 Section 196.25-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Searchlights § 196.25-1 Improper use prohibited. (a) No person shall flash or cause to be flashed the rays of...

  20. 46 CFR 196.25-1 - Improper use prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Improper use prohibited. 196.25-1 Section 196.25-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Searchlights § 196.25-1 Improper use prohibited. (a) No person shall flash or cause to be flashed the rays of...

  1. 22 CFR 19.6 - Court orders and divorce decrees.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Court orders and divorce decrees. 19.6 Section 19.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.6 Court orders and divorce decrees. ...

  2. 22 CFR 19.6 - Court orders and divorce decrees.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false Court orders and divorce decrees. 19.6 Section 19.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.6 Court orders and divorce decrees. ...

  3. 22 CFR 19.6 - Court orders and divorce decrees.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false Court orders and divorce decrees. 19.6 Section 19.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.6 Court orders and divorce decrees. ...

  4. 22 CFR 19.6 - Court orders and divorce decrees.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false Court orders and divorce decrees. 19.6 Section 19.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.6 Court orders and divorce decrees. ...

  5. 22 CFR 19.6 - Court orders and divorce decrees.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Court orders and divorce decrees. 19.6 Section 19.6 Foreign Relations DEPARTMENT OF STATE PERSONNEL BENEFITS FOR SPOUSES AND FORMER SPOUSES OF PARTICIPANTS IN THE FOREIGN SERVICE RETIREMENT AND DISABILITY SYSTEM § 19.6 Court orders and divorce decrees. ...

  6. 46 CFR 196.19-1 - Data required.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Data required. 196.19-1 Section 196.19-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Maneuvering Characteristics § 196.19-1 Data required. For each ocean and coastwise vessel of 1,600 gross tons or over, the...

  7. 46 CFR 196.19-1 - Data required.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Data required. 196.19-1 Section 196.19-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Maneuvering Characteristics § 196.19-1 Data required. For each ocean and coastwise vessel of 1,600 gross tons or over, the...

  8. 46 CFR 196.19-1 - Data required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Data required. 196.19-1 Section 196.19-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Maneuvering Characteristics § 196.19-1 Data required. For each ocean and coastwise vessel of 1,600 gross tons or over, the...

  9. 46 CFR 196.19-1 - Data required.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Data required. 196.19-1 Section 196.19-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Maneuvering Characteristics § 196.19-1 Data required. For each ocean and coastwise vessel of 1,600 gross tons or over, the...

  10. 46 CFR 196.19-1 - Data required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Data required. 196.19-1 Section 196.19-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Maneuvering Characteristics § 196.19-1 Data required. For each ocean and coastwise vessel of 1,600 gross tons or over, the...

  11. 46 CFR 196.37-25 - Emergency lights.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Emergency lights. 196.37-25 Section 196.37-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-25 Emergency lights. (a) All emergency...

  12. 46 CFR 196.37-25 - Emergency lights.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Emergency lights. 196.37-25 Section 196.37-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-25 Emergency lights. (a) All emergency...

  13. 46 CFR 196.37-25 - Emergency lights.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Emergency lights. 196.37-25 Section 196.37-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-25 Emergency lights. (a) All emergency...

  14. 46 CFR 196.37-25 - Emergency lights.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Emergency lights. 196.37-25 Section 196.37-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-25 Emergency lights. (a) All emergency...

  15. 46 CFR 196.37-25 - Emergency lights.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Emergency lights. 196.37-25 Section 196.37-25 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-25 Emergency lights. (a) All emergency...

  16. 27 CFR 28.196 - Consignment, shipment, and delivery.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... delivery. 28.196 Section 28.196 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Benefit of Drawback Filing of Notice and Removal § 28.196 Consignment, shipment, and delivery. The consignment, shipment, and delivery of distilled spirits removed under this subpart for export, use on...

  17. 27 CFR 28.196 - Consignment, shipment, and delivery.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... delivery. 28.196 Section 28.196 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... Benefit of Drawback Filing of Notice and Removal § 28.196 Consignment, shipment, and delivery. The consignment, shipment, and delivery of distilled spirits removed under this subpart for export, use on...

  18. 46 CFR 196.05-5 - Charts and nautical publications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Charts and nautical publications. 196.05-5 Section 196... OPERATIONS Notice to Mariners and Aids to Navigation § 196.05-5 Charts and nautical publications. As... publications necessary. 1 1 For United States vessels in or on the navigable waters of the United States,...

  19. 46 CFR 196.05-5 - Charts and nautical publications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Charts and nautical publications. 196.05-5 Section 196... OPERATIONS Notice to Mariners and Aids to Navigation § 196.05-5 Charts and nautical publications. As... publications necessary. 1 1 For United States vessels in or on the navigable waters of the United States,...

  20. 46 CFR 196.05-5 - Charts and nautical publications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Charts and nautical publications. 196.05-5 Section 196... OPERATIONS Notice to Mariners and Aids to Navigation § 196.05-5 Charts and nautical publications. As... publications necessary. 1 1 For United States vessels in or on the navigable waters of the United States,...

  1. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  2. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  3. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  4. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  5. 46 CFR 196.30-5 - Accidents to machinery.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Accidents to machinery. 196.30-5 Section 196.30-5... Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-5 Accidents to machinery. (a) In the event of an accident to a boiler, unfired pressure vessel, or machinery tending to render the further use...

  6. 46 CFR 196.37-7 - General alarm bells.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false General alarm bells. 196.37-7 Section 196.37-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-7 General alarm bells. (a) All general alarm bells...

  7. 46 CFR 196.37-15 - Firehose stations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Firehose stations. 196.37-15 Section 196.37-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-15 Firehose stations. (a) Each fire hydrant shall...

  8. 46 CFR 196.05-5 - Charts and nautical publications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Charts and nautical publications. 196.05-5 Section 196.05-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Notice to Mariners and Aids to Navigation § 196.05-5 Charts and nautical publications. As...

  9. 46 CFR 196.30-10 - Notice required before repair.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Notice required before repair. 196.30-10 Section 196.30-10 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Reports of Accidents, Repairs, and Unsafe Equipment § 196.30-10 Notice required before repair. (a...

  10. 46 CFR 196.37-23 - Hand portable fire extinguishers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Hand portable fire extinguishers. 196.37-23 Section 196.37-23 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-23 Hand portable fire...

  11. 46 CFR 196.05-1 - Duty of officers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Duty of officers. 196.05-1 Section 196.05-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Notice to Mariners and Aids to Navigation § 196.05-1 Duty of officers. (a) Licensed deck officers are...

  12. 46 CFR 196.15-60 - Firefighting equipment, general.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Firefighting equipment, general. 196.15-60 Section 196.15-60 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-60 Firefighting equipment, general. (a) It shall...

  13. 46 CFR 196.37-35 - Rudder orders.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Rudder orders. 196.37-35 Section 196.37-35 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-35 Rudder orders. (a) At all steering stations...

  14. 46 CFR 196.33-1 - When required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false When required. 196.33-1 Section 196.33-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Communication Between Deckhouses § 196.33-1 When required. On all vessels navigating in other than protected...

  15. 46 CFR 196.40-5 - Hull markings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Hull markings. 196.40-5 Section 196.40-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this chapter. ...

  16. 46 CFR 196.37-13 - Fire extinguishing system controls.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Fire extinguishing system controls. 196.37-13 Section 196.37-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-13 Fire extinguishing system...

  17. 46 CFR 196.15-20 - Hatches and other openings.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Hatches and other openings. 196.15-20 Section 196.15-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-20 Hatches and other openings. (a) It shall be the...

  18. 46 CFR 196.36-1 - When required.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false When required. 196.36-1 Section 196.36-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Display of Plans § 196.36-1 When required. (a) All manned vessels shall have permanently exhibited for the guidance...

  19. 46 CFR 196.20-1 - Unnecessary whistling prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Unnecessary whistling prohibited. 196.20-1 Section 196.20-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Whistling § 196.20-1 Unnecessary whistling prohibited. (a) The unnecessary sounding of the vessel...

  20. 46 CFR 196.40-15 - Load line marks.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Load line marks. 196.40-15 Section 196.40-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-15 Load line marks. (a) Vessels assigned a load line shall have the deck line...

  1. 46 CFR 196.15-18 - Loading doors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Loading doors. 196.15-18 Section 196.15-18 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Test, Drills, and Inspections § 196.15-18 Loading doors. (a) The master of a vessel fitted with loading doors...

  2. 46 CFR 196.27-1 - Master's and officer's responsibility.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Master's and officer's responsibility. 196.27-1 Section 196.27-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Lookouts § 196.27-1 Master's and officer's responsibility. (a) Nothing in this part...

  3. 46 CFR 196.80-1 - Master's responsibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Master's responsibility. 196.80-1 Section 196.80-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Explosive Handling Plan § 196.80-1 Master's responsibility. (a) It shall be the responsibility of the master...

  4. 46 CFR 196.27-1 - Master's and officer's responsibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Master's and officer's responsibility. 196.27-1 Section 196.27-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Lookouts § 196.27-1 Master's and officer's responsibility. (a) Nothing in this part...

  5. 32 CFR 196.130 - Effect of employment opportunities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Effect of employment opportunities. 196.130 Section 196.130 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE... FEDERAL FINANCIAL ASSISTANCE Introduction § 196.130 Effect of employment opportunities. The obligation...

  6. 46 CFR 196.15-18 - Loading doors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Loading doors. 196.15-18 Section 196.15-18 Shipping..., Drills, and Inspections § 196.15-18 Loading doors. (a) The master of a vessel fitted with loading doors shall assure that all loading doors are closed watertight and secured during the entire voyage except...

  7. 37 CFR 1.192-1.196 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false 1.192-1.196 Section 1.192-1.196 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... Patent Appeals and Interferences §§ 1.192-1.196 ...

  8. 37 CFR 1.192-1.196 - [Reserved

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false 1.192-1.196 Section 1.192-1.196 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... Trial and Appeal Board §§ 1.192-1.196 ...

  9. 37 CFR 1.192-1.196 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false 1.192-1.196 Section 1.192-1.196 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... Patent Appeals and Interferences §§ 1.192-1.196 ...

  10. 37 CFR 1.192-1.196 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false 1.192-1.196 Section 1.192-1.196 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... Patent Appeals and Interferences §§ 1.192-1.196 ...

  11. 37 CFR 1.192-1.196 - [Reserved

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false 1.192-1.196 Section 1.192-1.196 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF... Trial and Appeal Board §§ 1.192-1.196 ...

  12. 46 CFR 196.25-1 - Improper use prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Improper use prohibited. 196.25-1 Section 196.25-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Searchlights § 196.25-1 Improper use prohibited. (a) No person shall flash or cause to be flashed the rays of a...

  13. 46 CFR 196.25-1 - Improper use prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Improper use prohibited. 196.25-1 Section 196.25-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Searchlights § 196.25-1 Improper use prohibited. (a) No person shall flash or cause to be flashed the rays of a...

  14. 46 CFR 196.35-3 - Logbooks and records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Logbooks and records. 196.35-3 Section 196.35-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Logbook Entries § 196.35-3 Logbooks and records. (a) The master or person in charge of an...

  15. 46 CFR 196.34-15 - Shipboard stowage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Shipboard stowage. 196.34-15 Section 196.34-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-15 Shipboard stowage. (a) The approved buoyant work vests shall be stowed separately...

  16. 46 CFR 196.40-15 - Load line marks.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Load line marks. 196.40-15 Section 196.40-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-15 Load line marks. (a) Vessels assigned a load line shall have the deck...

  17. 46 CFR 196.33-1 - When required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false When required. 196.33-1 Section 196.33-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Communication Between Deckhouses § 196.33-1 When required. On all vessels navigating in other than...

  18. 46 CFR 196.40-5 - Hull markings.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Hull markings. 196.40-5 Section 196.40-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Markings on Vessels § 196.40-5 Hull markings. Vessels shall be marked as required by parts 67 and 69 of this chapter....

  19. 46 CFR 196.34-20 - Shipboard inspections.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Shipboard inspections. 196.34-20 Section 196.34-20 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-20 Shipboard inspections. (a) Each work vest shall be subject to examination by...

  20. 46 CFR 196.27-1 - Master's and officer's responsibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Master's and officer's responsibility. 196.27-1 Section 196.27-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Lookouts § 196.27-1 Master's and officer's responsibility. (a) Nothing in this...

  1. 46 CFR 196.20-1 - Unnecessary whistling prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Unnecessary whistling prohibited. 196.20-1 Section 196.20-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Whistling § 196.20-1 Unnecessary whistling prohibited. (a) The unnecessary sounding of the...

  2. 46 CFR 196.37-23 - Hand portable fire extinguishers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Hand portable fire extinguishers. 196.37-23 Section 196... VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-23 Hand portable fire extinguishers. (a) Each hand portable fire extinguisher shall be marked with a number and the location where...

  3. 46 CFR 196.37-23 - Hand portable fire extinguishers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Hand portable fire extinguishers. 196.37-23 Section 196... VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-23 Hand portable fire extinguishers. (a) Each hand portable fire extinguisher shall be marked with a number and the location where...

  4. 46 CFR 196.37-23 - Hand portable fire extinguishers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Hand portable fire extinguishers. 196.37-23 Section 196... VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-23 Hand portable fire extinguishers. (a) Each hand portable fire extinguisher shall be marked with a number and the location where...

  5. 46 CFR 196.37-23 - Hand portable fire extinguishers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Hand portable fire extinguishers. 196.37-23 Section 196... VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-23 Hand portable fire extinguishers. (a) Each hand portable fire extinguisher shall be marked with a number and the location where...

  6. 46 CFR 196.80-1 - Master's responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Master's responsibility. 196.80-1 Section 196.80-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Explosive Handling Plan § 196.80-1 Master's responsibility. (a) It shall be the responsibility of the...

  7. 27 CFR 41.196 - Power of attorney.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., § 41.196 was revised, effective Aug. 26, 2013 through Aug. 26, 2016. ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Power of attorney. 41.196 Section 41.196 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU,...

  8. 12 CFR 196.5 - Small market share exemption.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Small market share exemption. 196.5 Section 196.5 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MANAGEMENT OFFICIAL INTERLOCKS § 196.5 Small market share exemption. (a) Exemption. A management interlock that is prohibited...

  9. 12 CFR 196.5 - Small market share exemption.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Small market share exemption. 196.5 Section 196.5 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MANAGEMENT OFFICIAL INTERLOCKS § 196.5 Small market share exemption. (a) Exemption. A management interlock that is prohibited...

  10. 12 CFR 196.5 - Small market share exemption.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 1 2014-01-01 2014-01-01 false Small market share exemption. 196.5 Section 196.5 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY MANAGEMENT OFFICIAL INTERLOCKS § 196.5 Small market share exemption. (a) Exemption. A management interlock that is prohibited...

  11. 46 CFR 196.85-1 - Magazine operation and control.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Magazine operation and control. 196.85-1 Section 196.85... OPERATIONS Magazine Control § 196.85-1 Magazine operation and control. (a) Keys to magazine spaces and magazine chests shall be kept in the sole control or custody of the Master or one delegated...

  12. 46 CFR 196.37-47 - Portable magazine chests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Portable magazine chests. 196.37-47 Section 196.37-47... Markings for Fire and Emergency Equipment, etc. § 196.37-47 Portable magazine chests. (a) Portable magazine chests shall be marked in letters at least 3 inches high: PORTABLE MAGAZINE CHEST — FLAMMABLE —...

  13. 46 CFR 196.37-47 - Portable magazine chests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Portable magazine chests. 196.37-47 Section 196.37-47... Markings for Fire and Emergency Equipment, etc. § 196.37-47 Portable magazine chests. (a) Portable magazine chests shall be marked in letters at least 3 inches high: PORTABLE MAGAZINE CHEST — FLAMMABLE —...

  14. 46 CFR 196.85-1 - Magazine operation and control.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Magazine operation and control. 196.85-1 Section 196.85... OPERATIONS Magazine Control § 196.85-1 Magazine operation and control. (a) Keys to magazine spaces and magazine chests shall be kept in the sole control or custody of the Master or one delegated...

  15. 46 CFR 196.85-1 - Magazine operation and control.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Magazine operation and control. 196.85-1 Section 196.85... OPERATIONS Magazine Control § 196.85-1 Magazine operation and control. (a) Keys to magazine spaces and magazine chests shall be kept in the sole control or custody of the Master or one delegated...

  16. 46 CFR 196.85-1 - Magazine operation and control.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Magazine operation and control. 196.85-1 Section 196.85... OPERATIONS Magazine Control § 196.85-1 Magazine operation and control. (a) Keys to magazine spaces and magazine chests shall be kept in the sole control or custody of the Master or one delegated...

  17. 46 CFR 196.37-47 - Portable magazine chests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Portable magazine chests. 196.37-47 Section 196.37-47... Markings for Fire and Emergency Equipment, etc. § 196.37-47 Portable magazine chests. (a) Portable magazine chests shall be marked in letters at least 3 inches high: PORTABLE MAGAZINE CHEST — FLAMMABLE —...

  18. 46 CFR 196.37-47 - Portable magazine chests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Portable magazine chests. 196.37-47 Section 196.37-47... Markings for Fire and Emergency Equipment, etc. § 196.37-47 Portable magazine chests. (a) Portable magazine chests shall be marked in letters at least 3 inches high: PORTABLE MAGAZINE CHEST — FLAMMABLE —...

  19. 46 CFR 196.85-1 - Magazine operation and control.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Magazine operation and control. 196.85-1 Section 196.85... OPERATIONS Magazine Control § 196.85-1 Magazine operation and control. (a) Keys to magazine spaces and magazine chests shall be kept in the sole control or custody of the Master or one delegated...

  20. 46 CFR 196.37-47 - Portable magazine chests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Portable magazine chests. 196.37-47 Section 196.37-47... Markings for Fire and Emergency Equipment, etc. § 196.37-47 Portable magazine chests. (a) Portable magazine chests shall be marked in letters at least 3 inches high: PORTABLE MAGAZINE CHEST — FLAMMABLE —...

  1. Dipole Bands in {sup 196}Hg

    SciTech Connect

    Lawrie, J. J.; Lawrie, E. A.; Newman, R. T.; Sharpey-Schafer, J. F.; Smit, F. D.; Msezane, B.; Benatar, M.; Mabala, G. K.; Mutshena, K. P.; Federke, M.; Mullins, S. M.; Ncapayi, N. J.; Vymers, P.

    2011-10-28

    High spin states in {sup 196}Hg have been populated in the {sup 198}Pt({alpha},6n) reaction at 65 MeV and the level scheme has been extended. A new dipole band has been observed and a previously observed dipole has been confirmed. Excitation energies, spins and parities of these bands were determined from DCO ratio and linear polarization measurements. Possible quasiparticle excitations responsible for these structures are discussed.

  2. Advances in drug delivery system for platinum agents based combination therapy

    PubMed Central

    Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

    2015-01-01

    Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy. PMID:26779373

  3. Advances in drug delivery system for platinum agents based combination therapy.

    PubMed

    Kang, Xiang; Xiao, Hai-Hua; Song, Hai-Qin; Jing, Xia-Bin; Yan, Le-San; Qi, Ruo-Gu

    2015-12-01

    Platinum-based anticancer agents are widely used as first-line drugs in cancer chemotherapy for various solid tumors. However, great side effects and occurrence of resistance remain as the major drawbacks for almost all the platinum drugs developed. To conquer these problems, new strategies should be adopted for platinum drug based chemotherapy. Modern nanotechnology has been widely employed in the delivery of various therapeutics and diagnostic. It provides the possibility of targeted delivery of a certain anticancer drug to the tumor site, which could minimize toxicity and optimize the drug efficacy. Here, in this review, we focused on the recent progress in polymer based drug delivery systems for platinum-based combination therapy.

  4. Surface characterization of platinum electrodes.

    PubMed

    Solla-Gullón, José; Rodríguez, Paramaconi; Herrero, Enrique; Aldaz, Antonio; Feliu, Juan M

    2008-03-14

    The quantitative analysis of the different surface sites on platinum samples is attempted from pure voltammetric data. This analysis requires independent knowledge of the fraction of two-dimensional (111) and (100) domains. Specific site-probe reactions are employed to achieve this goal. Irreversibly-adsorbed bismuth and tellurium have been revealed to be sensitive to the presence of (111) terrace domains of different width whereas almost all sites involved in (100) ordered domains have been characterized through germanium adatoms. The experimental protocol follows that used with well-defined single-crystal electrodes and, therefore, requires careful control of the surface cleanliness. Platinum basal planes and their vicinal stepped surfaces have been employed to obtain calibration plots between the charge density measured under the adatom redox peak, specific for the type of surface site, and the corresponding terrace size. The evaluation of the (100) bidimensional domains can also be achieved using the voltammetric profiles, once the fraction of (111) ordered domains present in the polyoriented platinum has been determined and their featureless contribution has been subtracted from the whole voltammetric response. Using that curve, it is possible to perform a deconvolution of the adsorption states of the polycrystalline sample different from those related to (111) domains. The fraction of (100)-related states in the deconvoluted voltammogram can then be compared to that expected from the independent estimation coming from the charge involved in the redox process undergone by the irreversibly-adsorbed germanium and thus check the result of the deconvolution. The information about the surface-site distribution can also be applied to analyze the voltammetric profile of nanocrystalline platinum electrodes.

  5. Request for Correction 11001 Toxicological Review of Halogenated Platinum Salts and Platinum Compounds

    EPA Pesticide Factsheets

    Request for Correction by the International Platinum Group Metals Association seeking the correction of information disseminated in the draft EPA document Toxicological Review of Halogenated Platinum Salts and Platinum Compounds: In Support of Summary Information on the Integrated Risk Information System (IRIS).

  6. Phosphoric acid fuel cell platinum use study

    NASA Technical Reports Server (NTRS)

    Lundblad, H. L.

    1983-01-01

    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.

  7. Process of [sup 196]Hg enrichment

    DOEpatents

    Grossman, M.W.; Mellor, C.E.

    1993-04-27

    A simple rate equation model shows that by increasing the length of the photochemical reactor and/or by increasing the photon intensity in said reactor, the feedstock utilization of [sup 196]Hg will be increased. Two preferred embodiments of the present invention are described, namely (1) long reactors using long photochemical lamps and vapor filters; and (2) quartz reactors with external UV reflecting films. These embodiments have each been constructed and operated, demonstrating the enhanced utilization process dictated by the mathematical model (also provided).

  8. Process of .sup.196 Hg enrichment

    DOEpatents

    Grossman, Mark W.; Mellor, Charles E.

    1993-01-01

    A simple rate equation model shows that by increasing the length of the photochemical reactor and/or by increasing the photon intensity in said reactor, the feedstock utilization of .sup.196 Hg will be increased. Two preferred embodiments of the present invention are described, namely (1) long reactors using long photochemical lamps and vapor filters; and (2) quartz reactors with external UV reflecting films. These embodiments have each been constructed and operated, demonstrating the enhanced utilization process dictated by the mathematical model (also provided).

  9. IPD-196, a novel phosphatidylinositol 3-kinase inhibitor with potent anticancer activity against hepatocellular carcinoma.

    PubMed

    Lee, Ju-Hee; Lee, Hyunseung; Yun, Sun-Mi; Jung, Kyung Hee; Jeong, Yujeong; Yan, Hong Hua; Hong, Sungwoo; Hong, Soon-Sun

    2013-02-01

    As the activation of phosphatidylinositol 3-kinase (PI3K) is associated with a wide variety of human malignancies, it is emerging as an attractive target for cancer treatment. In this study we synthesized a novel PI3Kα inhibitor, IPD-196 [ethyl 6-(5-(2,4-difluorophenylsulfonamido)pyridin-3-yl)imidazo[1,2-a]pyridine-3-carboxylate], and evaluated its anticancer effects on human hepatocellular carcinoma (HCC) cells. IPD-196 effectively inhibited the phosphorylation of downstream PI3K effectors such as Akt, mTOR, p70S6K, and 4E-BP1, and its antiproliferative effect was more potent than that of sorafenib or LY294002. It also induced cell cycle arrest at the G0/G1 phase as well as apoptosis by increasing the proportion of sub-G1 apoptotic cells, and the levels of cleaved PARP, caspase-3, and caspase-9. Furthermore, it decreased the expression of HIF-1α and VEGF in Huh-7 cells, and inhibited tube formation and migration of human umbilical vein endothelial cells, which was confirmed by a Matrigel plug assay in mice. Taken together, IPD-196 exhibited its anticancer activity through disruption of the PI3K/Akt pathway that caused cell cycle arrest, apoptosis induction, and inhibition of angiogenesis in human HCC cells. We therefore suggest that IPD-196 may be a potential candidate drug for targeted HCC therapy.

  10. Design, Synthesis of Novel Platinum(II) Glycoconjugates, and Evaluation of Their Antitumor Effects.

    PubMed

    Han, Jianbin; Gao, Xiangqian; Liu, Ran; Yang, Jinna; Zhang, Menghua; Mi, Yi; Shi, Ying; Gao, Qingzhi

    2016-06-01

    A new series of sugar-conjugated (trans-R, R-cyclohexane-1, 2-diamine)-2-halo-malonato-platinum(II) complexes were designed and synthesized to target tumor-specific glucose transporters (GLUTs). The water solubility of the sugar-conjugated platinum (II) complexes was greatly improved by average of 570-fold, 33-fold, and 94-fold, respectively, compared to cisplatin (1.0 mg/mL), carboplatin (17.1 mg/mL), and the newest generation of clinical drug oxaliplatin (6.0 mg/mL). Despite the high water solubility, the platinum(II) glycoconjugates exhibited a notable increase in cytotoxicity by a margin of 1.5- to 6.0-fold in six different human cancer cell lines with respect to oxaliplatin. The potential GLUT1 transportability of the complexes was investigated through a molecular docking study and was confirmed with GLUT1 inhibitor-mediated cytotoxicity dependency evaluation. The results showed that the sugar-conjugated platinum(II) complexes can be recognized by the glucose recognition binding site of GLUT1 and their cell killing effect depends highly on the GLUT1 inhibitor, quercetin. The research presenting a prospective concept for targeted therapy anticancer drug design, and with the analysis of the synthesis, water solubility, antitumor activity, and the transportability of the platinum(II) glycoconjugates, this study provides fundamental data supporting the inherent potential of these designed conjugates as lead compounds for GLUT-mediated tumor targeting.

  11. Overexpression of MAC30 is Resistant to Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer.

    PubMed

    Chen, Ruhua; Fen, Yan; Lin, Xubo; Ma, Tieliang; Cai, Hourong; Ding, Hui

    2016-12-01

    Adjuvant platinum-based chemotherapy has developed its stability as the first-line treatment in advanced non-small cell lung cancer (NSCLC). The objective of this study was to investigate the prognostic value of meningioma-associated protein (MAC30) on adjuvant platinum-based chemotherapeutic response and survival in patients with NSCLC. A total of 174 retrospective stage III B to IV Chinese patients with NSCLC were enrolled in the study. Among all cases, 85 patients were given platinum-based chemotherapy and another 89 patients received molecularly targeted therapy. The expression of MAC30 in tumor samples was confirmed via immunohistochemical staining to correlate with the therapeutic response and survival of patients. Patients having NSCLC with MAC30 overexpression showed a poorer response to platinum-based chemotherapy, while there was no prognostic value of MAC30 expression on molecularly targeted therapy. Further, patients receiving platinum-based chemotherapy with enhanced MAC30 expression exhibited shorter survival. A multivariate analysis exhibited that increased MAC30 expression was an independent prognostic factor for overall survival in patients having NSCLC with platinum-based chemotherapy. In conclusion, patients having NSCLC with higher MAC30 expression resisted to platinum-based chemotherapy and exhibited worse survival. © The Author(s) 2015.

  12. Platinum electrodes for electrochemical detection of bacteria

    NASA Technical Reports Server (NTRS)

    Wilkins, J. R.

    1979-01-01

    Bacteria is detected electro-chemically by measuring evolution of hydrogen in test system with platinum and reference electrode. Using system, electrodes of platinum are used to detect and enumerate varieties of gram-positive and gram-negative organisms compared in different media.

  13. Mouse Model of Halogenated Platinum Salt Hypersensitivity

    EPA Science Inventory

    Occupational exposure to halogenated platinum salts can trigger the development of asthma. Concern for increased asthma risk exists for the general population due to the use of platinum (Pt) in catalytic converters and its emerging use as a diesel fuel additive. To investigate a...

  14. Failure mechanism characterization of platinum alloy

    NASA Technical Reports Server (NTRS)

    Rosen, J. M.; Mcfarlen, W. T.

    1986-01-01

    This article describes procedures and results of testing performed on a platinum/10-percent rhodium, thin-wall tubular product. The purpose of the testing was to develop exemplar SEM fractographs to be used to characterize failures under various environmental conditions. Conditions evaluated for the platinum alloys included high temperature, hydrogen environment, braze metal contamination, and cyclic loading.

  15. Mouse Model of Halogenated Platinum Salt Hypersensitivity

    EPA Science Inventory

    Occupational exposure to halogenated platinum salts can trigger the development of asthma. Concern for increased asthma risk exists for the general population due to the use of platinum (Pt) in catalytic converters and its emerging use as a diesel fuel additive. To investigate a...

  16. Aurora Kinase A expression predicts platinum-resistance and adverse outcome in high-grade serous ovarian carcinoma patients.

    PubMed

    Mignogna, Chiara; Staropoli, Nicoletta; Botta, Cirino; De Marco, Carmela; Rizzuto, Antonia; Morelli, Michele; Di Cello, Annalisa; Franco, Renato; Camastra, Caterina; Presta, Ivan; Malara, Natalia; Salvino, Angela; Tassone, Pierfrancesco; Tagliaferri, Pierosandro; Barni, Tullio; Donato, Giuseppe; Di Vito, Anna

    2016-05-21

    High-Grade Serous Ovarian Carcinoma (HGSOC) is the predominant histotype of epithelial ovarian cancer (EOC), characterized by advanced stage at diagnosis, frequent TP53 mutation, rapid progression, and high responsiveness to platinum-based-chemotherapy. To date, standard first-line-chemotherapy in advanced EOC includes platinum salts and paclitaxel with or without bevacizumab. The major prognostic factor is the response duration from the end of the platinum-based treatment (platinum-free interval) and about 10-0 % of EOC patients bear a platinum-refractory disease or develop early resistance (platinum-free interval shorter than 6 months). On these bases, a careful selection of patients who could benefit from chemotherapy is recommended to avoid unnecessary side effects and for a better disease outcome. In this retrospective study, an immunohistochemical evaluation of Aurora Kinase A (AURKA) was performed on 41 cases of HGSOC according to platinum-status. Taking into account the number and intensity of AURKA positive cells we built a predictive score able to discriminate with high accuracy platinum-sensitive patients from platinum-resistant patients (p < 0.001). Furthermore, we observed that AURKA overexpression correlates to worse overall survival (p = 0.001; HR 0.14). We here suggest AURKA as new effective tool to predict the biological behavior of HGSOC. Particularly, our results indicate that AURKA has a role both as predictor of platinum-resistance and as prognostic factor, that deserves further investigation in prospective clinical trials. Indeed, in the era of personalized medicine, AURKA could assist the clinicians in selecting the best treatment and represent, at the same time, a promising new therapeutic target in EOC treatment.

  17. Chemical and Electrochemical Synthesis of Platinum Black.

    PubMed

    Stanca, S E; Hänschke, F; Ihring, A; Zieger, G; Dellith, J; Kessler, E; Meyer, H-G

    2017-04-21

    We present electrochemical and chemical synthesis of platinum black at room temperature in aqueous and non-aqueous media. X-ray analysis established the purity and crystalline nature. The electron micrographs indicate that the nanostructures consist of platinum crystals that interconnect to form porous assemblies. Additionally, the electron micrographs of the platinum black thin layer, which was electrochemically deposited on different metallic and semiconductive substrates (aluminium, platinum, silver, gold, tin-cooper alloy, indium-tin-oxide, stainless steel, and copper), indicate that the substrate influences its porous features but not its absorbance characteristics. The platinum black exhibited a broad absorbance and low reflectance in the ultraviolet, visible, and infrared regions. These characteristics make this material suitable for use as a high-temperature resistant absorber layer for the fabrication of microelectronics.

  18. 46 CFR 196.15-55 - Requirements for fuel oil.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Requirements for fuel oil. 196.15-55 Section 196.15-55... Test, Drills, and Inspections § 196.15-55 Requirements for fuel oil. (a) It shall be the duty of the chief engineer to cause an entry in the log to be made of each supply of fuel oil received on...

  19. 46 CFR 196.15-55 - Requirements for fuel oil.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Requirements for fuel oil. 196.15-55 Section 196.15-55... Test, Drills, and Inspections § 196.15-55 Requirements for fuel oil. (a) It shall be the duty of the chief engineer to cause an entry in the log to be made of each supply of fuel oil received on...

  20. 46 CFR 196.15-55 - Requirements for fuel oil.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Requirements for fuel oil. 196.15-55 Section 196.15-55... Test, Drills, and Inspections § 196.15-55 Requirements for fuel oil. (a) It shall be the duty of the chief engineer to cause an entry in the log to be made of each supply of fuel oil received on...

  1. 46 CFR 196.15-55 - Requirements for fuel oil.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Requirements for fuel oil. 196.15-55 Section 196.15-55... Test, Drills, and Inspections § 196.15-55 Requirements for fuel oil. (a) It shall be the duty of the chief engineer to cause an entry in the log to be made of each supply of fuel oil received on...

  2. 46 CFR 196.15-55 - Requirements for fuel oil.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Requirements for fuel oil. 196.15-55 Section 196.15-55... Test, Drills, and Inspections § 196.15-55 Requirements for fuel oil. (a) It shall be the duty of the chief engineer to cause an entry in the log to be made of each supply of fuel oil received on board...

  3. 32 CFR 196.545 - Pre-employment inquiries.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Pre-employment inquiries. 196.545 Section 196... Prohibited § 196.545 Pre-employment inquiries. (a) Marital status. A recipient shall not make pre-employment...” or “Mrs.” (b) Sex. A recipient may make pre-employment inquiry as to the sex of an applicant...

  4. 32 CFR 196.545 - Pre-employment inquiries.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Pre-employment inquiries. 196.545 Section 196... Prohibited § 196.545 Pre-employment inquiries. (a) Marital status. A recipient shall not make pre-employment...” or “Mrs.” (b) Sex. A recipient may make pre-employment inquiry as to the sex of an applicant...

  5. 32 CFR 196.545 - Pre-employment inquiries.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Pre-employment inquiries. 196.545 Section 196... Prohibited § 196.545 Pre-employment inquiries. (a) Marital status. A recipient shall not make pre-employment...” or “Mrs.” (b) Sex. A recipient may make pre-employment inquiry as to the sex of an applicant...

  6. 32 CFR 196.545 - Pre-employment inquiries.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Pre-employment inquiries. 196.545 Section 196... Prohibited § 196.545 Pre-employment inquiries. (a) Marital status. A recipient shall not make pre-employment...” or “Mrs.” (b) Sex. A recipient may make pre-employment inquiry as to the sex of an applicant...

  7. MicroRNA-196a and -196b as Potential Biomarkers for the Early Detection of Familial Pancreatic Cancer

    PubMed Central

    Slater, Emily P.; Strauch, Konstantin; Rospleszcz, Susanne; Ramaswamy, Annette; Esposito, Irene; Klöppel, Günter; Matthäi, Elvira; Heeger, Kristin; Fendrich, Volker; Langer, Peter; Bartsch, Detlef K.

    2014-01-01

    Screening programs are recommended for individuals at risk (IAR) from families with familial pancreatic cancer (FPC). However, reliable imaging methods or biomarkers for early diagnosis of pancreatic ductal adenocarcinoma (PC) or its precursor lesions are still lacking. The ability of circulating microRNAs (miRNAs) to discriminate multifocal high-grade precursor lesions or PC from normal was examined. The presence of miRNA-21, -155, -196a, -196b and -210 was analyzed in the serum of transgenic KPC mice to test their ability to distinguish mice with different grades of pancreatic intraepithelial neoplasia (mPanIN1–3) or PC from control mice. Serum levels of miR-196a and -196b were significantly higher in mice with PanIN2/3 lesions (n = 10) or PC (n = 8) as compared to control mice (n = 10) or mice with PanIN1 lesions (n = 10; P = .01). In humans, miR-196a and -196b were also diagnostic. Patients with PC, sporadic (n = 9) or hereditary (n = 10), and IAR with multifocal PanIN2/3 lesions (n = 5) had significantly higher serum levels than patients with neuroendocrine pancreatic tumors (n = 10) or chronic pancreatitis (n = 10), IAR with PanIN1 or no PanIN lesions (n = 5), and healthy controls (n = 10). The combination of both miR-196a and -196b reached a sensitivity of 1 and specificity of 0.9 (area under the curve = 0.99) to diagnose PC or high-grade PanIN lesions. In addition, preoperative elevated serum levels of miR-196a and -196b in patients with PC or multifocal PanIN2/3 lesions dropped to normal after potential curative resection. The combination of miR-196a and -196b may be a promising biomarker test for the screening of IAR for FPC. PMID:24956938

  8. MicroRNA-196a Is a Potential Marker of Progression during Barrett’s Metaplasia-Dysplasia-Invasive Adenocarcinoma Sequence in Esophagus

    PubMed Central

    Maru, Dipen M.; Singh, Rajesh R.; Hannah, Christina; Albarracin, Constance T.; Li, Yong X.; Abraham, Ronald; Romans, Angela M.; Yao, Hui; Luthra, Madan G.; Anandasabapathy, Sharmila; Swisher, Stephen G.; Hofstetter, Wayne L.; Rashid, Asif; Luthra, Rajyalakshmi

    2009-01-01

    Barrett’s esophagus (BE)/Barrett’s metaplasia (BM) is a recognized precursor of esophageal adenocarcinoma (EA) with an intermediary stage of dysplasia. The low yield and high cost of endoscopic screening of patients with BE underscores the need for novel biomarkers, such as microRNA (miRNA), which have emerged as important players in neoplastic progression for risk assessment of developing dysplasia/adenocarcinoma. Recently, we reported highly elevated levels of miRNA-196a (miR-196a) in EA and demonstrated its growth-promoting and anti-apoptotic functions. Here, we evaluated miR-196a as a marker of BE progression to low-grade dysplasia, high-grade dysplasia, and EA using microdissected paraffin-embedded tissues from 11 patients. Higher levels of miR-196a were observed in EA, BE, and dysplastic lesions compared with normal squamous mucosa, and in high-grade dysplasia compared with BE and low-grade dysplasia. Using frozen tumor tissues from 10 additional patients who had advanced EA, we evaluated the correlation of miR-196a with its in silico-predicted targets, keratin 5 (KRT5), small proline-rich protein 2C (SPRR2C), and S100 calcium-binding protein A9 (S100A9), which are down-regulated during BE progression. MiR-196a levels inversely correlated with the predicted target mRNA levels in EA. We confirmed that miR-196a specifically targets KRT5, SPRR2C, and S100A9 3′ UTRs using miR-196a-mimic and luciferase reporter-based assays. In conclusion, this study identified miR-196a as a potential marker of progression of BE and KRT5, SPRR2C, and S100A9 as its targets. PMID:19342367

  9. Modelling oxide formation and growth on platinum

    NASA Astrophysics Data System (ADS)

    Baroody, Heather A.; Jerkiewicz, Gregory; Eikerling, Michael H.

    2017-04-01

    We present a mathematical model of oxide formation and growth on platinum. The motivation stems from the necessity to understand platinum dissolution in the cathode catalyst layer of polymer electrolyte fuel cells. As is known, platinum oxide formation and reduction are strongly linked to platinum dissolution processes. However, a consistent model of the oxidation processes on platinum does not exist. Our oxide growth model links interfacial exchange processes between platinum and oxygen ions with the transport of oxygen ion vacancies via diffusion and migration. A parametric analysis is performed to rationalize vital trends in oxide growth kinetics. The rate determining step of oxide formation and growth is identified as the extraction of platinum atoms at the metal-oxide interface. A kinetic effect is observed while adjusting the potential when growing the oxide layer, and the solution indicates that a structural change occurs at high potentials, around 1.5 VRHE. The model compares well to experimental data for various materials from various sources.

  10. Platinum for neural stimulation: voltammetry considerations.

    PubMed

    Hudak, E M; Mortimer, J T; Martin, H B

    2010-04-01

    The underlying cause of electrical stimulation-induced tissue trauma is debated. Our focus has been to study effects of generating electrochemical by-products at the electrode-electrolyte interface, using the pulse-clamp technique coupled with voltammetry to analyze charge transfer. The platinum-H(2)SO(4) system has been a standard for analyzing electrochemistry on platinum-stimulating electrodes, even though the chemical differences between H(2)SO(4) and the living body are obvious. Experiments were designed to determine whether phosphate-buffered saline (PBS) could serve as a more accurate emulation of living tissue. It had been rumored that platinum's performance in PBS deviates from that in H(2)SO(4) at larger potentials. Voltammetry in PBS was performed in two potential ranges. In a conventional potential range (-0.6 V to +0.9 V versus Ag/AgCl), characteristic peaks appear very similar to published voltammograms of platinum in H(2)SO(4). However, in an extended range (-1.0 V to +1.7 V versus Ag/AgCl), platinum exhibited additional electrochemical activity: one oxidation peak and two reduction peaks. Therefore, voltammetry was performed in NaCl and a sodium phosphate mixture (i.e. PBS components) to separate their activity. The altered electrochemical performance of platinum in PBS suggests that certain reactions on platinum at potentials outside the water window will not reflect what happens in vivo.

  11. Characterization of electrochemically modified polycrystalline platinum surfaces

    SciTech Connect

    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.

  12. Characterization of electrochemically modified polycrystalline platinum surfaces

    SciTech Connect

    Krebs, Leonard 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 -0.24 and +1.25 VSCE 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.

  13. Inhibition of constitutive signal transducer and activator of transcription 3 activation by novel platinum complexes with potent antitumor activity.

    PubMed

    Turkson, James; Zhang, Shumin; Palmer, Jay; Kay, Heidi; Stanko, Joseph; Mora, Linda B; Sebti, Said; Yu, Hua; Jove, Richard

    2004-12-01

    DNA-alkylating agents that are platinum complexes induce apoptotic responses and have wide application in cancer therapy. The potential for platinum compounds to modulate signal transduction events that contribute to their therapeutic outcome has not been extensively examined. Among the signal transducer and activator of transcription (STAT) proteins, Stat3 activity is frequently up-regulated in many human tumors. Various lines of evidence have established a causal role for aberrant Stat3 activity in malignant transformation and provided validation for its targeting in the development of small-molecule inhibitors as novel cancer therapeutics. We report here that platinum-containing compounds disrupt Stat3 signaling and suppress its biological functions. The novel platinum (IV) compounds, CPA-1, CPA-7, and platinum (IV) tetrachloride block Stat3 activity in vitro at low micromolar concentrations. In malignant cells that harbor constitutively activated Stat3, CPA-1, CPA-7, and platinum (IV) tetrachloride inhibit cell growth and induce apoptosis in a manner that reflects the attenuation of persistent Stat3 activity. By contrast, cells that do not contain persistent Stat3 activity are marginally affected or are not affected by these compounds. Moreover, CPA-7 induces the regression of mouse CT26 colon tumor, which correlates with the abrogation of persistent Stat3 activity in tumors. Thus, the modulation of oncogenic signal transduction pathways, such as Stat3, may be one of the key molecular mechanisms for the antitumor effects of platinum (IV)-containing complexes.

  14. [Mechanism of Platinum Derivatives Induced Kidney Injury].

    PubMed

    Yan, Feifei; Duan, Jianchun; Wang, Jie

    2015-09-20

    Platinum derivatives are the most widely used chemotherapeutic agents to treat solid tumors including ovarian, head and neck, and testicular germ cell tumors, lung cancer, and colorectal cancer. Two major problems exist, however, in the clinic use of platinum derivatives. One is the development of tumor resistance to the drug during therapy, leading to treatment failure. The other is the drug's toxicity such as the cisplatin's nephrotoxicity, which limits the dose that can be administered. This paper describes the mechanism of platinum derivatives induced kidney injury.

  15. Antitumor effect of arabinogalactan and platinum complex.

    PubMed

    Starkov, A K; Zamay, T N; Savchenko, A A; Ingevatkin, E V; Titova, N M; Kolovskaya, O S; Luzan, N A; Silkin, P P; Kuznetsova, S A

    2016-03-01

    The article presents the results of investigation of antitumor properties of platinum-arabinogalactan complex. We showed the ability of the complex to inhibit the growth of Ehrlich ascites tumor cells. It is found that the distribution of the platinum-arabinogalactan complex is not specific only for tumor cells in mice. The complex was found in all tissues and organs examined (ascites cells, embryonic cells, kidney, and liver). The mechanism of action of the arabinogalactan-platinum complex may be similar to cisplatin as the complex is able to accumulate in tumor cells.

  16. Stabilizing platinum in phosphoric acid fuel cells

    NASA Astrophysics Data System (ADS)

    Remick, R. J.

    1981-10-01

    A carbon substrate for use in fabricating phosphoric acid fuel cell cathodes was modified by catalytic oxidation to stabilize the platinum catalyst by retarding the sintering of small platinum crystallites. Results of 100-hour operational tests confirmed that the rate of platinum surface area loss observed on catalytically oxidized supports was less than that observed with unmodified supports of the same starting material. Fuel cell electrodes fabricated from Vulcan XC-72R, which was modified by catalytic in a nitric oxide atmosphere, produced low platium sintering rates and high activity for the reduction of oxygen in the phosphoric acid environment.

  17. Catalytic reforming with rhenium-platinum catalyst containing more rhenium than platinum

    SciTech Connect

    Gallagher, J.P.; Yarrington, R.M.

    1982-10-26

    A new reforming process employs a new rhenium-platinum catalytic composite having a rhenium to platinum weight ratio in the range of not less than 2 to about 5, whereby longer relative cycle length is obtained when reforming a naphtha having less than about 0.5 ppm by weight of sulfur than if the rhenium-platinum ratio is outside of such range.

  18. 27 CFR 41.196 - Power of attorney.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Power of attorney. 41.196 Section 41.196 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND...

  19. 27 CFR 41.196 - Power of attorney.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Power of attorney. 41.196 Section 41.196 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS AND TUBES, AND...

  20. 21 CFR 133.196 - Swiss cheese for manufacturing.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Swiss cheese for manufacturing. 133.196 Section... Standardized Cheese and Related Products § 133.196 Swiss cheese for manufacturing. Swiss cheese for manufacturing conforms to the definition and standard of identity prescribed for swiss cheese by §...

  1. 21 CFR 133.196 - Swiss cheese for manufacturing.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Swiss cheese for manufacturing. 133.196 Section... Standardized Cheese and Related Products § 133.196 Swiss cheese for manufacturing. Swiss cheese for manufacturing conforms to the definition and standard of identity prescribed for swiss cheese by §...

  2. 21 CFR 133.196 - Swiss cheese for manufacturing.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Swiss cheese for manufacturing. 133.196 Section... Standardized Cheese and Related Products § 133.196 Swiss cheese for manufacturing. Swiss cheese for manufacturing conforms to the definition and standard of identity prescribed for swiss cheese by §...

  3. 21 CFR 133.196 - Swiss cheese for manufacturing.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Swiss cheese for manufacturing. 133.196 Section... Standardized Cheese and Related Products § 133.196 Swiss cheese for manufacturing. Swiss cheese for manufacturing conforms to the definition and standard of identity prescribed for swiss cheese by §...

  4. 21 CFR 133.196 - Swiss cheese for manufacturing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false Swiss cheese for manufacturing. 133.196 Section... Standardized Cheese and Related Products § 133.196 Swiss cheese for manufacturing. Swiss cheese for manufacturing conforms to the definition and standard of identity prescribed for swiss cheese by §...

  5. 22 CFR 196.1 - What is the Fellowship Program?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 22 Foreign Relations 1 2014-04-01 2014-04-01 false What is the Fellowship Program? 196.1 Section... FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.1 What is the Fellowship Program? The Thomas R. Pickering Foreign Affairs/Graduate Foreign Affairs Fellowship Program is designed to...

  6. 22 CFR 196.1 - What is the Fellowship Program?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 22 Foreign Relations 1 2011-04-01 2011-04-01 false What is the Fellowship Program? 196.1 Section... FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.1 What is the Fellowship Program? The Thomas R. Pickering Foreign Affairs/Graduate Foreign Affairs Fellowship Program is designed to...

  7. 22 CFR 196.1 - What is the Fellowship Program?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false What is the Fellowship Program? 196.1 Section... FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.1 What is the Fellowship Program? The Thomas R. Pickering Foreign Affairs/Graduate Foreign Affairs Fellowship Program is designed to...

  8. 22 CFR 196.1 - What is the Fellowship Program?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 22 Foreign Relations 1 2013-04-01 2013-04-01 false What is the Fellowship Program? 196.1 Section... FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.1 What is the Fellowship Program? The Thomas R. Pickering Foreign Affairs/Graduate Foreign Affairs Fellowship Program is designed to...

  9. 22 CFR 196.1 - What is the Fellowship Program?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false What is the Fellowship Program? 196.1 Section... FOREIGN AFFAIRS/GRADUATE FOREIGN AFFAIRS FELLOWSHIP PROGRAM § 196.1 What is the Fellowship Program? The Thomas R. Pickering Foreign Affairs/Graduate Foreign Affairs Fellowship Program is designed to...

  10. 46 CFR 196.37-13 - Fire extinguishing system controls.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... DIOXIDE FIRE APPARATUS,” or “FOAM FIRE APPARATUS,” etc., as the case may be. ... 46 Shipping 7 2011-10-01 2011-10-01 false Fire extinguishing system controls. 196.37-13 Section... VESSELS OPERATIONS Markings for Fire and Emergency Equipment, etc. § 196.37-13 Fire extinguishing system...

  11. 40 CFR 417.196 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Pretreatment standards for new sources. 417.196 Section 417.196 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars...

  12. 40 CFR 417.196 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 29 2011-07-01 2009-07-01 true Pretreatment standards for new sources. 417.196 Section 417.196 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars...

  13. 40 CFR 417.196 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 30 2013-07-01 2012-07-01 true Pretreatment standards for new sources. 417.196 Section 417.196 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars...

  14. 40 CFR 417.196 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 29 2014-07-01 2012-07-01 true Pretreatment standards for new sources. 417.196 Section 417.196 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars...

  15. 40 CFR 417.196 - Pretreatment standards for new sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Pretreatment standards for new sources. 417.196 Section 417.196 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars...

  16. 46 CFR 196.35-3 - Logbooks and records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Logbooks and records. 196.35-3 Section 196.35-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS... research vessel that is required by 46 U.S.C. 11301 to have an official logbook may maintain the logbook on...

  17. 10 CFR 205.196 - Statement of objections.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Statement of objections. 205.196 Section 205.196 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable Violation, Remedial Order... that is filed by the person to whom a Proposed Remedial Order is directed shall include a copy of...

  18. 10 CFR 205.196 - Statement of objections.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Statement of objections. 205.196 Section 205.196 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable Violation, Remedial Order... that is filed by the person to whom a Proposed Remedial Order is directed shall include a copy of...

  19. 32 CFR 196.520 - Job classification and structure.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Job classification and structure. 196.520... Activities Prohibited § 196.520 Job classification and structure. A recipient shall not: (a) Classify a job... progression, seniority systems, career ladders, or tenure systems for similar jobs, position descriptions, or...

  20. 32 CFR 196.520 - Job classification and structure.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Job classification and structure. 196.520... Activities Prohibited § 196.520 Job classification and structure. A recipient shall not: (a) Classify a job... progression, seniority systems, career ladders, or tenure systems for similar jobs, position descriptions, or...

  1. 32 CFR 196.520 - Job classification and structure.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Job classification and structure. 196.520... Activities Prohibited § 196.520 Job classification and structure. A recipient shall not: (a) Classify a job... progression, seniority systems, career ladders, or tenure systems for similar jobs, position descriptions, or...

  2. 32 CFR 196.520 - Job classification and structure.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Job classification and structure. 196.520... Activities Prohibited § 196.520 Job classification and structure. A recipient shall not: (a) Classify a job... progression, seniority systems, career ladders, or tenure systems for similar jobs, position descriptions, or...

  3. 32 CFR 196.520 - Job classification and structure.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Job classification and structure. 196.520... Activities Prohibited § 196.520 Job classification and structure. A recipient shall not: (a) Classify a job... progression, seniority systems, career ladders, or tenure systems for similar jobs, position descriptions, or...

  4. 32 CFR 196.125 - Effect of other requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Effect of other requirements. 196.125 Section... FEDERAL FINANCIAL ASSISTANCE Introduction § 196.125 Effect of other requirements. (a) Effect of other... regulation. (b) Effect of State or local law or other requirements. The obligation to comply with these...

  5. 42 CFR 460.196 - Disclosure of review results.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Disclosure of review results. 460.196 Section 460... ELDERLY (PACE) Federal/State Monitoring § 460.196 Disclosure of review results. (a) CMS and the State administering agency promptly report the results of reviews under §§ 460.190 and 460.192 to the PACE...

  6. 36 CFR 223.196 - Civil penalties for violation

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Civil penalties for violation 223.196 Section 223.196 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER, SPECIAL FOREST PRODUCTS, AND FOREST...

  7. 36 CFR 223.196 - Civil penalties for violation

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Civil penalties for violation 223.196 Section 223.196 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER, SPECIAL FOREST PRODUCTS, AND FOREST...

  8. 32 CFR 196.130 - Effect of employment opportunities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Effect of employment opportunities. 196.130 Section 196.130 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Introduction...

  9. 32 CFR 196.125 - Effect of other requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Effect of other requirements. 196.125 Section 196.125 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Introduction §...

  10. 36 CFR 223.196 - Civil penalties for violation

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Civil penalties for violation 223.196 Section 223.196 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND DISPOSAL OF NATIONAL FOREST SYSTEM TIMBER The Forest Resources Conservation and Shortage...

  11. 32 CFR 196.435 - Employment assistance to students.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Employment assistance to students. 196.435... Prohibited § 196.435 Employment assistance to students. (a) Assistance by recipient in making available... available to any of its students: (1) Shall assure itself that such employment is made available...

  12. 32 CFR 196.435 - Employment assistance to students.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Employment assistance to students. 196.435... Prohibited § 196.435 Employment assistance to students. (a) Assistance by recipient in making available... available to any of its students: (1) Shall assure itself that such employment is made available...

  13. 32 CFR 196.435 - Employment assistance to students.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Employment assistance to students. 196.435... Prohibited § 196.435 Employment assistance to students. (a) Assistance by recipient in making available... available to any of its students: (1) Shall assure itself that such employment is made available...

  14. 32 CFR 196.435 - Employment assistance to students.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Employment assistance to students. 196.435... Prohibited § 196.435 Employment assistance to students. (a) Assistance by recipient in making available... available to any of its students: (1) Shall assure itself that such employment is made available...

  15. 32 CFR 196.435 - Employment assistance to students.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Employment assistance to students. 196.435... Prohibited § 196.435 Employment assistance to students. (a) Assistance by recipient in making available... available to any of its students: (1) Shall assure itself that such employment is made available...

  16. 46 CFR 196.37-13 - Fire extinguishing system controls.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Fire extinguishing system controls. 196.37-13 Section 196.37-13 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH... controls. The control cabinets or spaces containing valves, manifolds, or controls for the various...

  17. 46 CFR 196.27-1 - Master's and officer's responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Master's and officer's responsibility. 196.27-1 Section... VESSELS OPERATIONS Lookouts § 196.27-1 Master's and officer's responsibility. (a) Nothing in this part shall exonerate any master or officer in command from the consequences of any neglect to keep a...

  18. 46 CFR 196.01-1 - General; preemptive effect.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false General; preemptive effect. 196.01-1 Section 196.01-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS... State or local regulations in the same field. ...

  19. 46 CFR 196.01-1 - General; preemptive effect.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false General; preemptive effect. 196.01-1 Section 196.01-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS... State or local regulations in the same field. ...

  20. Comparison of the effects of the oral anticancer platinum(IV) complexes oxoplatin and metabolite cis-diammine-tetrachlorido-platinum(IV) on global gene expression of NCI-H526 cells

    PubMed Central

    Olszewski, Ulrike; Ulsperger, Ernst; Geissler, Klaus; Hamilton, Gerhard

    2011-01-01

    Platinum(IV) coordination complexes like oxoplatin (cis,cis,trans-diammine-dichlorido-dihydroxido-platinum[IV]) show high stability and therefore can be utilized orally for outpatient care. Although oxoplatin is capable of binding directly to DNA after prolonged incubation, platinum(IV) agents are considered to be largely inert prodrugs that are converted to highly cytotoxic platinum(II) compounds by reducing substances, enzymes, or microenviron-mental conditions. Reaction of oxoplatin with 0.1 M hydrogen chloride mimicking gastric acid yields cis-diammine-tetrachlorido-platinum(IV) (DATCP[IV]), which exhibits two-fold increased activity. The presence of chlorides as ligands in the axial position results in a high reduction potential that favors transformation to platinum(II) complexes. In this study, the intracellular effect of the highly reactive tetrachlorido derivative was investigated in comparison with an equipotent dose of cisplatin. Genome-wide expression profiling of NCI-H526 small cell lung cancer cells treated with these platinum species revealed clear differences in the expression pattern of affected genes and concerned cellular pathways between DATCP(IV) and cisplatin. Application of DATCP(IV) resulted in extensive downregulation of protein and ATP synthesis, cell cycle regulation, and glycolysis, in contrast to cisplatin, which preferentially targeted glutathione conjugation, pyruvate metabolism, citric acid cycle, and the metabolism of amino acids and a range of carbohydrates. Thus, the oxoplatin metabolite DATCP(IV) constitutes a potent cytotoxic derivative that may be produced by gastric acid or acidic areas prevailing in larger solid tumors, depending on the respective pharmaceutical formulation of oxoplatin. Furthermore, DATCP(IV) exhibits intracellular effects that are clearly different from the expected reduced product cisplatin(II). In conclusion, activation of the platinum(IV) complex oxoplatin seems to involve the generation of a cytotoxic

  1. Comparison of the effects of the oral anticancer platinum(IV) complexes oxoplatin and metabolite cis-diammine-tetrachlorido-platinum(IV) on global gene expression of NCI-H526 cells.

    PubMed

    Olszewski, Ulrike; Ulsperger, Ernst; Geissler, Klaus; Hamilton, Gerhard

    2011-01-01

    Platinum(IV) coordination complexes like oxoplatin (cis,cis,trans-diammine-dichlorido-dihydroxido-platinum[IV]) show high stability and therefore can be utilized orally for outpatient care. Although oxoplatin is capable of binding directly to DNA after prolonged incubation, platinum(IV) agents are considered to be largely inert prodrugs that are converted to highly cytotoxic platinum(II) compounds by reducing substances, enzymes, or microenviron-mental conditions. Reaction of oxoplatin with 0.1 M hydrogen chloride mimicking gastric acid yields cis-diammine-tetrachlorido-platinum(IV) (DATCP[IV]), which exhibits two-fold increased activity. The presence of chlorides as ligands in the axial position results in a high reduction potential that favors transformation to platinum(II) complexes. In this study, the intracellular effect of the highly reactive tetrachlorido derivative was investigated in comparison with an equipotent dose of cisplatin. Genome-wide expression profiling of NCI-H526 small cell lung cancer cells treated with these platinum species revealed clear differences in the expression pattern of affected genes and concerned cellular pathways between DATCP(IV) and cisplatin. Application of DATCP(IV) resulted in extensive downregulation of protein and ATP synthesis, cell cycle regulation, and glycolysis, in contrast to cisplatin, which preferentially targeted glutathione conjugation, pyruvate metabolism, citric acid cycle, and the metabolism of amino acids and a range of carbohydrates. Thus, the oxoplatin metabolite DATCP(IV) constitutes a potent cytotoxic derivative that may be produced by gastric acid or acidic areas prevailing in larger solid tumors, depending on the respective pharmaceutical formulation of oxoplatin. Furthermore, DATCP(IV) exhibits intracellular effects that are clearly different from the expected reduced product cisplatin(II). In conclusion, activation of the platinum(IV) complex oxoplatin seems to involve the generation of a cytotoxic

  2. Combinations of platinums and selected phytochemicals as a means of overcoming resistance in ovarian cancer.

    PubMed

    Huq, Fazlul; Yu, Jun Q; Beale, Philip; Chan, Charles; Arzuman, Lalia; Nessa, Meher U; Mazumder, Mohammed E H

    2014-01-01

    Cancer sufferers are often found to use herbal products along with targeted therapy although not much information (whether beneficial or harmful) is available about the effects of such combinations. In this study, we investigated synergism from the combination of platinum drugs and a number of tumour-active phytochemicals including curcumin, epigallocatechin-3-gallate, thymoquinone, genistein, resveratrol, betulinic acid and ursolic acid in three human ovarian cancer cell lines A2780, A2780(cisR) and A2780(ZD0473R), as a function of concentration and the sequence of administration. Both the dose-effect curves and combination indices show that the binary combinations of platinum drugs with the phytochemicals exert concentration- and sequence-dependent synergism in the cell lines. Generally the degree of synergism is found to be greater in sequenced administration such as 0/2 h, 2/0 h, 0/4 h and 4/0 h than the bolus. The variation in the nature of the combined drug action from being highly synergistic to antagonistic with the change in sequence of administration clearly indicates that the action of one drug modulates that of the other (towards the induction or inhibition of apoptosis). We have also used sequenced combinations of platinum drugs and bortezomib (a proteasome inhibitor that prevents cisplatin-induced proteasomal degration of copper transporter CTR1) to enhance cellular platinum accumulation and the level of platinum-DNA binding especially in the resistant human ovarian tumour models. Proteomic studies to identify the key proteins associated with platinum resistance are ongoing. We have identified 59 proteins associated with platinum resistance in ovarian tumor models.

  3. Platinum metals magmatic sulfide ores.

    PubMed

    Naldrett, A J; Duke, J M

    1980-06-27

    Platinum-group elements (PGE) are mined predominantly from deposits that have formed by the segregation of molten iron-nickel-copper sulfides from silicate magmas. The absolute concentrations of PGE in sulfides from different deposits vary over a range of five orders of magnitude, whereas those of other chalcophile elements vary by factors of only 2 to 100. However, the relative proportions of the different PGE in a given deposit are systematically related to the nature of the parent magma. The absolute and relative concentrations of PGE in magmatic sulfides are explained in terms of the degree of partial melting of mantle peridotite required to produce the parent magma and the processes of batch equilibration and fractional segregation of sulfides. The Republic of South Africa and the U.S.S.R. together possess more than 97 percent of the world PGE reserves, but significant undeveloped resources occur in North America. The Stillwater complex in Montana is perhaps the most important example.

  4. Photoelectron holography of platinum (111)

    SciTech Connect

    Petersen, B.L.; Terminello, L.J.; Barton, J.J.; Shirley, D.A.

    1993-04-01

    Platinum atoms near a (111) single-crystal face have been imaged using photoelectron holography. Electron angular intensity patterns were collected at equally spaced wavenumbers from 6 to 12{Angstrom}{sup {minus}1}. Images of atoms near expected atomic positions are obtained from single-wavenumber analyses over the range of the data set. Positions are detected further from the emitter than we have seen previously, and symmetry assumptions are not required. We have also adopted a three dimensional means of representing the data in order to help understand the results. Twin image suppression and artifact reduction in the holographically reconstructed data are set are obtained when images at different wavenumbers are correctly phase-summed. We are assessing the capability of the technique for rendering true three-dimensional structural information for unknown systems.

  5. Teaching the Chemistry of Platinum.

    PubMed

    Anderson, Robert G W

    2015-01-01

    Following colonisation of South America by the Spanish, many new naturally occurring substances were sent to Europe. One of these was the silvery, unreactive metal, platinum, discovered in New Grenada in the mid-eighteenth century. It was often found in granular form, associated with gold, and the challenge to chemists was to refine it, produce it as wire or sheet, and determine its chemical properties. This interested the professor of chemistry at the University of Edinburgh, Joseph Black, who was able to obtain samples from London-based Spanish contacts, particularly Ignacio Luzuriaga. This paper examines how Black transmitted his knowledge of the metal to large numbers of students attending his annual course.

  6. Calibration of platinum resistance thermometers.

    NASA Technical Reports Server (NTRS)

    Sinclair, D. H.; Terbeek, H. G.; Malone, J. H.

    1972-01-01

    Results of five years experience in calibrating about 1000 commercial platinum resistance thermometers (PRT) are reported. These PRT were relatively small and rugged, with ice-point resistances from 200 to 5000 ohms. Calibrations normalized in terms of resistance-difference ratios (Cragoe Z function) were found to be remarkably uniform for five of six different types of PRT tested, and to agree very closely with normalized calibrations of the primary reference standard type PRT. The Z function normalization cancels residual resistances which are not temperature dependent and simplifies interpolation between calibration points when the quality of a given type of PRT has been established in terms of uniform values of the Z function. Measurements at five or six well spaced base-point temperatures with Z interpolation will suffice to calibrate a PRT accurately from 4 to 900 K.

  7. Evaluation of platinum resistance thermometers

    NASA Technical Reports Server (NTRS)

    Daryabeigi, Kamran; Dillon-Townes, Lawrence A.

    1988-01-01

    An evaluation procedure for the characterization of industrial platinum resistance thermometers (PRTs) for use in the temperature range -120 to 160 C was investigated. This evaluation procedure consisted of calibration, thermal stability and hysteresis testing of four surface measuring PRTs. Five different calibration schemes were investigated for these sensors. The IPTS-68 formulation produced the most accurate result, yielding average sensor systematic error of 0.02 C and random error of 0.1 C. The sensors were checked for thermal stability by successive and thermal cycling between room temperature, 160 C, and boiling point of nitrogen. All the PRTs suffered from instability and hysteresis. The applicability of the self-heating technique as an in situ method for checking the calibration of PRTs located inside wind tunnels was investigated.

  8. Evaluation of platinum resistance thermometers

    NASA Technical Reports Server (NTRS)

    Daryabeigi, Kamran; Dillon-Townes, Lawrence A.

    1988-01-01

    An evaluation procedure for the characterization of industrial platinum resistance thermometers (PRTs) for use in the temperature range -120 to 160 C was investigated. This evaluation procedure consisted of calibration, thermal stability and hysteresis testing of four surface measuring PRTs. Five different calibration schemes were investigated for these sensors. The IPTS-68 formulation produced the most accurate result, yielding average sensor systematic error of 0.02 C and random error of 0.1 C. The sensors were checked for thermal stability by successive and thermal cycling between room temperature, 160 C, and boiling point of nitrogen. All the PRTs suffered from instability and hysteresis. The applicability of the self-heating technique as an in situ method for checking the calibration of PRTs located inside wind tunnels was investigated.

  9. Calibration of platinum resistance thermometers.

    NASA Technical Reports Server (NTRS)

    Sinclair, D. H.; Terbeek, H. G.; Malone, J. H.

    1972-01-01

    Results of five years experience in calibrating about 1000 commercial platinum resistance thermometers (PRT) are reported. These PRT were relatively small and rugged, with ice-point resistances from 200 to 5000 ohms. Calibrations normalized in terms of resistance-difference ratios (Cragoe Z function) were found to be remarkably uniform for five of six different types of PRT tested, and to agree very closely with normalized calibrations of the primary reference standard type PRT. The Z function normalization cancels residual resistances which are not temperature dependent and simplifies interpolation between calibration points when the quality of a given type of PRT has been established in terms of uniform values of the Z function. Measurements at five or six well spaced base-point temperatures with Z interpolation will suffice to calibrate a PRT accurately from 4 to 900 K.

  10. Low Expression of miR-196b Enhances the Expression of BCR-ABL1 and HOXA9 Oncogenes in Chronic Myeloid Leukemogenesis

    PubMed Central

    Liu, Yue; Zheng, Wenling; Song, Yanbin; Ma, Wenli; Yin, Hong

    2013-01-01

    MicroRNAs (miRNAs) can function as tumor suppressors or oncogene promoters during tumor development. In this study, low levels of expression of miR-196b were detected in patients with chronic myeloid leukemia. Bisulfite genomic sequencing PCR and methylation-specific PCR were used to examine the methylation status of the CpG islands in the miR-196b promoter in K562 cells, patients with leukemia and healthy individuals. The CpG islands showed more methylation in patients with chronic myeloid leukemia compared with healthy individuals (P<0.05), which indicated that low expression of miR-196b may be associated with an increase in the methylation of CpG islands. The dual-luciferase reporter assay system demonstrated that BCR-ABL1 and HOXA9 are the target genes of miR-196b, which was consistent with predictions from bioinformatics software analyses. Further examination of cell function indicated that miR-196b acts to reduce BCR-ABL1 and HOXA9 protein levels, decrease cell proliferation rate and retard the cell cycle. A low level of expression of miR-196b can cause up-regulation of BCR-ABL1 and HOXA9 expression, which leads to the development of chronic myeloid leukemia. MiR-196b may represent an effective target for chronic myeloid leukemia therapy. PMID:23894305

  11. Stabilizing platinum in phosphoric acid fuel cells

    NASA Technical Reports Server (NTRS)

    Remick, R. J.

    1981-01-01

    The cathode of the phosphoric acid fuel cell uses a high surface area platinum catalyst supported on a carbon substrate. During operation, the small platinum crystallites sinter, causing loss in cell performance. A support was developed that stabilizes platinum in the high surface area condition by retarding or preventing the sintering process. The approach is to form etch pits in the carbon by oxidizing the carbon in the presence of a metal oxide catalyst, remove the metal oxide by an acid wash, and then deposit platinum in these pits. Results confirm the formation of etch pits in each of the three supports chosen for investigation: Vulcan XC-72R, Vulcan XC-72 that was graphized at 2500 C, and Shawinigan Acetylene Black.

  12. Platinum-ruthenium-palladium fuel cell electrocatalyst

    DOEpatents

    Gorer, Alexander

    2006-02-07

    A catalyst suitable for use in a fuel cell, especially as an anode catalyst, that contains platinum at a concentration that is between about 20 and about 60 atomic percent, ruthenium at a concentration that is between about 20 and about 60 atomic percent, palladium at a concentration that is between about 5 and about 45 atomic percent, and having an atomic ratio of platinum to ruthenium that is between about 0.7 and about 1.2. Alternatively, the catalyst may contain platinum at a concentration that is between about 25 and about 50 atomic percent, ruthenium at a concentration that is between about 25 and about 55 atomic percent, palladium at a concentration that is between about 5 and about 45 atomic percent, and having a difference between the concentrations of ruthenium and platinum that is no greater than about 20 atomic percent.

  13. Platinum-ruthenium-nickel fuel cell electrocatalyst

    DOEpatents

    Gorer, Alexander

    2005-07-26

    A catalyst suitable for use in a fuel cell, especially as an anode catalyst, that contains platinum, ruthenium, and nickel, wherein the nickel is at a concentration that is less than about 10 atomic percent.

  14. VB Platinum Tile & Carpet, Inc. Information Sheet

    EPA Pesticide Factsheets

    VB Platinum Tile & Carpet, Inc. (the Company) is located in Bristow, Virginia. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Washington, DC.

  15. Platinum-Resistor Differential Temperature Sensor

    NASA Technical Reports Server (NTRS)

    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.

  16. Fate of platinum metals in the environment.

    PubMed

    Pawlak, Justyna; Łodyga-Chruścińska, Elżbieta; Chrustowicz, Jakub

    2014-07-01

    For many years now automotive exhaust catalysts have been used to reduce the significant amounts of harmful chemical substances generated by car engines, such as carbon monoxide, nitrogen oxides, and aromatic hydrocarbons. Although they considerably decrease environmental contamination with the above-mentioned compounds, it is known that catalysts contribute to the environmental load of platinum metals (essential components of catalysts), which are released with exhaust fumes. Contamination with platinum metals stems mainly from automotive exhaust converters, but other major sources also exist. Since platinum group elements (PGEs): platinum (Pt), palladium (Pd), rhodium (Rh), ruthenium (Ru) and iridium (Ir) seem to spread in the environment and accumulate in living organisms, they may pose a threat to animals and humans. This paper discusses the modes and forms of PGE emission as well as their impact on the environment and living organisms.

  17. Stabilizing platinum in phosphoric acid fuel cells

    NASA Technical Reports Server (NTRS)

    Remick, R. J.

    1982-01-01

    Platinum sintering on phosphoric acid fuel cell cathodes is discussed. The cathode of the phosphoric acid fuel cell uses a high surface area platinum catalyst dispersed on a conductive carbon support to minimize both cathode polarization and fabrication costs. During operation, however, the active surface area of these electrodes decreases, which in turn leads to decreased cell performance. This loss of active surface area is a major factor in the degradation of fuel cell performance over time.

  18. Acquired platinum resistance involves epithelial to mesenchymal transition through ubiquitin ligase FBXO32 dysregulation

    PubMed Central

    Tanaka, Nobuyuki; Miyazaki, Yasumasa; Mikami, Shuji; Niwa, Naoya; Otsuka, Yutaro; Mizuno, Ryuichi; Kikuchi, Eiji; Miyajima, Akira; Sabe, Hisataka; Okada, Yasunori; Suematsu, Makoto; Oya, Mototsugu

    2016-01-01

    To identify the molecules involved in epithelial to mesenchymal transition (EMT) in urothelial carcinoma (UC) after acquisition of platinum resistance, here we examined the changes in global gene expression before and after platinum treatment. Four invasive UC cell lines, T24, 5637, and their corresponding sublines T24PR and 5637PR with acquired platinum resistance, were assessed by microarray, and the ubiquitin E3 ligase FBXO32 was newly identified as a negative regulator of EMT in UC tumors after acquisition of platinum resistance. In vitro and in vivo studies showed an intimate relationship between FBXO32 expression and EMT, demonstrating that FBXO32 dysregulation in T24PR cells results in elevated expression of the mesenchymal molecules SNAIL and vimentin and decreased expression of the epithelial molecule E-cadherin. The association between FBXO32 expression and EMT was further validated using clinical samples. Knockdown of MyoD expression, a specific target of FBXO32 polyubiquitination, revealed upregulation of E-cadherin expression and downregulation of SNAIL and vimentin expression in T24PR cells. Comparative genomic hybridization array analysis demonstrated loss of heterozygosity at 8q24.13 in T24PR cells, which harbors FBXO32. Our findings suggest the importance of the association between EMT and ubiquitin-proteasome regulation when tumors develop acquired platinum resistance. PMID:27812537

  19. Acquired platinum resistance involves epithelial to mesenchymal transition through ubiquitin ligase FBXO32 dysregulation.

    PubMed

    Tanaka, Nobuyuki; Kosaka, Takeo; Miyazaki, Yasumasa; Mikami, Shuji; Niwa, Naoya; Otsuka, Yutaro; Minamishima, Yoji Andrew; Mizuno, Ryuichi; Kikuchi, Eiji; Miyajima, Akira; Sabe, Hisataka; Okada, Yasunori; Uhlén, Per; Suematsu, Makoto; Oya, Mototsugu

    2016-11-03

    To identify the molecules involved in epithelial to mesenchymal transition (EMT) in urothelial carcinoma (UC) after acquisition of platinum resistance, here we examined the changes in global gene expression before and after platinum treatment. Four invasive UC cell lines, T24, 5637, and their corresponding sublines T24PR and 5637PR with acquired platinum resistance, were assessed by microarray, and the ubiquitin E3 ligase FBXO32 was newly identified as a negative regulator of EMT in UC tumors after acquisition of platinum resistance. In vitro and in vivo studies showed an intimate relationship between FBXO32 expression and EMT, demonstrating that FBXO32 dysregulation in T24PR cells results in elevated expression of the mesenchymal molecules SNAIL and vimentin and decreased expression of the epithelial molecule E-cadherin. The association between FBXO32 expression and EMT was further validated using clinical samples. Knockdown of MyoD expression, a specific target of FBXO32 polyubiquitination, revealed upregulation of E-cadherin expression and downregulation of SNAIL and vimentin expression in T24PR cells. Comparative genomic hybridization array analysis demonstrated loss of heterozygosity at 8q24.13 in T24PR cells, which harbors FBXO32. Our findings suggest the importance of the association between EMT and ubiquitin-proteasome regulation when tumors develop acquired platinum resistance.

  20. Platinum-based chemotherapy: gastrointestinal immunomodulation and enteric nervous system toxicity.

    PubMed

    Stojanovska, Vanesa; Sakkal, Samy; Nurgali, Kulmira

    2015-02-15

    The efficacy of chemotherapeutic treatment of colorectal cancer is challenged by severe gastrointestinal side effects, which include nausea, vomiting, constipation, and diarrhea. These symptoms can persist long after the treatment has been ceased. An emerging concept is the ability of platinum-based drugs to stimulate immunity, which is in contrast to conventional chemotherapeutic agents that are immunosuppressive. Here, we review the immunomodulatory aspects of platinum-based anticancer chemotherapeutics and their impact on gastrointestinal innervation. Given the bidirectional communication between the enteric nervous system and gastrointestinal immune system; exploring the consequences of platinum-induced immunogenicity will facilitate better understanding of gut dysfunction caused by chemotherapeutic agents. We propose that the development of future successful chemotherapeutics should rely on targeting the mechanisms underlying long-term gastrointestinal side effects.

  1. Downregulation of microRNA-196a enhances the sensitivity of non-small cell lung cancer cells to cisplatin treatment.

    PubMed

    Li, Qian; Yang, Zailiang; Chen, Mingyan; Liu, Ying

    2016-04-01

    MicroRNAs (miRNAs or miRs) are a class of small, non-coding RNA molecules that play an important role in the pathogenesis of human diseases through the regulation of gene expression. Although miRNA-196a has been implicated in the progression of human lung cancer, its role in enhancing the sensitivity of non‑small cell lung cancer (NSCLC) cells to cisplatin has not yet been confirmed. The aim of this study was to evaluate the effects of miRNA‑196a on the sensitivity of NSCLC cells to cisplatin in vitro and in vivo. RT-qPCR was used to detect miRNA-196a expression. Synthesized locked nucleic acid (LNA)-anti‑miRNA-196a oligonucleotide was transiently transfected into the SPC‑A‑1 and A549 lung cancer cells to examine the effects of miRNA‑196a on the growth of and colony formation inthe cisplatin‑treated cells. The effects of miRNA-196a on the sensitivity of SPC‑A-1 cells to cisplatin in vivo were determined using BALB/c nude mice. The expression of miRNA‑196a was significantly higher in both the lung cancer tissues and cell lines. The LNA-based knockdown of miRNA-196a significantly inhibited SPC‑A‑1 and A549 cell growth and induced apoptosis. Moreover, the downregulation of miRNA-196a sensitized the SPC‑A‑1 and A549 NSCLC cells to cisplatin in vitro and in vivo, by inducing apoptosis. The findings of this study demonstrate that the administration of cisplatin in combination with miRNA-196a-targeted therapy may be a potential therapeutic strategy for the treatment of NSCLC.

  2. MicroRNA miR-196a controls melanoma-associated genes by regulating HOX-C8 expression.

    PubMed

    Mueller, Daniel W; Bosserhoff, Anja-Katrin

    2011-09-01

    Resulting from a screening for microRNAs differentially regulated in melanocytes and melanoma cells, we found expression of miR-196a to be significantly down-regulated in malignant melanoma cell lines and tissue samples. As it was stated before that miR-196a might negatively regulate expression of the transcription factor HOX-C8, we analyzed HOX-C8 levels in NHEMs and melanoma cells and found a strong up-regulation of HOX-C8 expression in malignant melanoma cell lines and tissue samples compared with melanocytes. Several HOX-C8 target genes are known to be involved in processes such as oncogenesis, cell adhesion, proliferation and apoptosis. We, therefore, aimed to further investigate a potential "miR-196a → HOX-C8 → HOX-C8 target gene" relationship. Stable transfection with an miR-196a expression plasmid led to strong down-regulation of HOX-C8 expression in melanoma cells. Luciferase assays using reporter plasmids containing different fragments of the HOX-C8 3'UTR confirmed direct interactions of miR-196a with the HOX-C8 mRNA. Focusing on target genes of HOX-C8, which might play an important role in melanomagenesis, we identified three genes (cadherin-11, calponin-1 and osteopontin) that are up- or down-regulated, respectively, by altered HOX-C8 expression in miR-196a expressing cell clones and are thus indirectly regulated by this microRNA. As those target genes are closely related to important cellular mechanisms such as cell adhesion, cytoskeleton remodeling, tumor formation and invasive behavior of tumor cells, altered miR-196a expression exerts strong effects contributing to tumor cell transformation and formation and progression of malignant melanoma. This fact is underlined by a strongly reduced invasive behavior of melanoma cells re-expressing miR-196a in vitro.

  3. Collectivity of {sup 196}Po at low spin

    SciTech Connect

    Grahn, T.; Page, R. D.; Dewald, A.; Jolie, J.; Melon, B.; Pissulla, Th.; Greenlees, P. T.; Jakobsson, U.; Jones, P.; Julin, R.; Juutinen, S.; Ketelhut, S.; Leino, M.; Nyman, M.; Peura, P.; Rahkila, P.; Saren, J.; Scholey, C.; Sorri, J.; Uusitalo, J.

    2009-07-15

    Absolute electromagnetic transition probabilities in {sup 196}Po have been measured using the recoil distance Doppler-shift technique. The lifetimes of the three lowest yrast states in {sup 196}Po were extracted from singles {gamma}-ray spectra by using the recoil-decay tagging method. In addition, configuration mixing calculations of angular momentum projected mean-field states have been carried out for {sup 196}Po. The present study sheds light on the onset of collectivity and mixing of competing structures in neutron-deficient Po nuclei.

  4. Targeted theranostic platinum(IV) prodrug with a built-in aggregation-induced emission light-up apoptosis sensor for noninvasive early evaluation of its therapeutic responses in situ.

    PubMed

    Yuan, Youyong; Kwok, Ryan T K; Tang, Ben Zhong; Liu, Bin

    2014-02-12

    Targeted drug delivery to tumor cells with minimized side effects and real-time in situ monitoring of drug efficacy is highly desirable for personalized medicine. In this work, we report the synthesis and biological evaluation of a chemotherapeutic Pt(IV) prodrug whose two axial positions are functionalized with a cyclic arginine-glycine-aspartic acid (cRGD) tripeptide for targeting integrin αvβ3 overexpressed cancer cells and an apoptosis sensor which is composed of tetraphenylsilole (TPS) fluorophore with aggregation-induced emission (AIE) characteristics and a caspase-3 enzyme specific Asp-Glu-Val-Asp (DEVD) peptide. The targeted Pt(IV) prodrug can selectively bind to αvβ3 integrin overexpressed cancer cells to facilitate cellular uptake. In addition, the Pt(IV) prodrug can be reduced to active Pt(II) drug in cells and release the apoptosis sensor TPS-DEVD simultaneously. The reduced Pt(II) drug can induce the cell apoptosis and activate caspase-3 enzyme to cleave the DEVD peptide sequence. Due to free rotation of the phenylene rings, TPS-DEVD is nonemissive in aqueous media. The specific cleavage of DEVD by caspase-3 generates the hydrophobic TPS residue, which tends to aggregate, resulting in restriction of intramolecular rotations of the phenyl rings and ultimately leading to fluorescence enhancement. Such noninvasive and real-time imaging of drug-induced apoptosis in situ can be used as an indicator for early evaluation of the therapeutic responses of a specific anticancer drug.

  5. Platinum in Earth surface environments

    NASA Astrophysics Data System (ADS)

    Reith, F.; Campbell, S. G.; Ball, A. S.; Pring, A.; Southam, G.

    2014-04-01

    Platinum (Pt) is a rare precious metal that is a strategic commodity for industries in many countries. The demand for Pt has more than doubled in the last 30 years due to its role in the catalytic conversion of CO, hydrocarbons and NOx in modern automobiles. To explore for new Pt deposits, process ores and deal with ecotoxicological effects of Pt mining and usage, the fundamental processes and pathways of Pt dispersion and re-concentration in surface environments need to be understood. Hence, the aim of this review is to develop a synergistic model for the cycling of Pt in Earth surface environments. This is achieved by integrating the geological/(biogeo)chemical literature, which focuses on naturally occurring Pt mobility around ore deposits, with the environmental/ecotoxicological literature dealing with anthropogenic Pt dispersion. In Pt deposits, Pt occurs as sulfide-, telluride- and arsenide, native metal and alloyed to other PGEs and iron (Fe). Increased mining and utilization of Pt combined with the burning of fossil fuels have led to the dispersion of Pt-containing nano- and micro-particles. Hence, soils and sediments in industrialized areas, urban environments and along major roads are now commonly Pt enriched. Platinum minerals, nuggets and anthropogenic particles are transformed by physical and (bio)geochemical processes. Complexation of Pt ions with chloride, thiosulfate, ammonium, cyanide, low- and high molecular weight organic acids (LMWOAs and HMWOAs) and siderophores can facilitate Pt mobilization. Iron-oxides, clays, organic matter and (micro)biota are known to sequester Pt-complexes and -particles. Microbes and plants are capable of bioaccumulating and reductively precipitating mobile Pt complexes. Bioaccumulation can lead to toxic effects on plants and animals, including humans. (Bio)mineralization in organic matter-rich sediments can lead to the formation of secondary Pt particles and -grains. Ultimately, Pt is enriched in oceanic sediments

  6. G196 epitope tag system: a novel monoclonal antibody, G196, recognizes the small, soluble peptide DLVPR with high affinity

    PubMed Central

    Tatsumi, Kasumi; Sakashita, Gyosuke; Nariai, Yuko; Okazaki, Kosuke; Kato, Hiroaki; Obayashi, Eiji; Yoshida, Hisashi; Sugiyama, Kanako; Park, Sam-Yong; Sekine, Joji; Urano, Takeshi

    2017-01-01

    The recognition specificity of monoclonal antibodies (mAbs) has made mAbs among the most frequently used tools in both basic science research and in clinical diagnosis and therapies. Precise determination of the epitope allows the development of epitope tag systems to be used with recombinant proteins for various purposes. Here we describe a new family of tag derived from the epitope recognized by a highly specific mAb G196. The minimal epitope was identified as the five amino acid sequence Asp-Leu-Val-Pro-Arg. Permutation analysis was used to characterize the binding requirements of mAb G196, and the variable regions of the mAb G196 were identified and structurally analyzed by X-ray crystallography. Isothermal titration calorimetry revealed the high affinity (Kd = 1.25 nM) of the mAb G196/G196-epitope peptide interaction, and G196-tag was used to detect several recombinant cytosolic and nuclear proteins in human and yeast cells. mAb G196 is valuable for developing a new peptide tagging system for cell biology and biochemistry research. PMID:28266535

  7. Biologically Inspired Phosphino Platinum Complexes

    SciTech Connect

    Jain, Avijita; Helm, Monte L.; Linehan, John C.; DuBois, Daniel L.; Shaw, Wendy J.

    2012-08-01

    Platinum complexes containing phosphino amino acid and amino acid ester ligands, built upon the PPhNR’2 platform, have been synthesized and characterized (PPhNR’2= [1,3-diaza]-5-phenyl phosphacyclohexane, R’=glycine or glycine ester). These complexes were characterized by 31P, 13C, 1H, 195Pt NMR spectroscopy and mass spectrometry. The X-ray crystal structure of one of the complexes, [PtCl2(PPhNGlyester 2)2], is also reported. These biologically inspired ligands have potential use in homogeneous catalysis, with special applications in chiral chemistry and water soluble chemistry. These complexes also provide a foundation upon which larger peptides can be attached, to allow the introduction of enzyme-like features onto small molecule catalysts. This work was supported by the US Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory is operated by Battelle for the US Department of Energy.

  8. 42 CFR 460.196 - Disclosure of review results.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Federal/State Monitoring § 460.196 Disclosure of review results. (a) CMS and the...

  9. 42 CFR 460.196 - Disclosure of review results.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) Federal/State Monitoring § 460.196 Disclosure of review results. (a) CMS and the...

  10. Epirubicin, Cisplatin, and Capecitabine for Primary Platinum-Resistant or Platinum-Refractory Epithelial Ovarian Cancer

    PubMed Central

    Sayal, Karen; Gounaris, Ioannis; Basu, Bristi; Freeman, Sue; Moyle, Penny; Hosking, Karen; Iddawela, Mahesh; Jimenez-Linan, Mercedes; Abraham, Jean; Brenton, James; Hatcher, Helen; Earl, Helena; Parkinson, Christine

    2015-01-01

    Objective Primary platinum-resistant epithelial ovarian cancer (EOC) is an area of unmet medical need. There is limited evidence from small studies that platinum-based combinations can overcome “resistance” in a proportion of patients. We investigated the efficacy and toxicity of platinum-based combination chemotherapy in the platinum-resistant and platinum-refractory setting. Methods Epirubicin, cisplatin, and capecitabine (ECX) combination chemotherapy was used at our institution for the treatment of relapsed EOC. From the institutional database, we identified all patients with primary platinum-refractory or platinum-resistant relapse treated with ECX as second-line therapy between 2001 and 2012. We extracted demographic, clinical, treatment, and toxicity data and outcomes. We used logistic and Cox regression models to identify predictors of response and survival respectively. Results Thirty-four 34 patients (8 refractory, 26 resistant) were treated with ECX. Response Evaluation Criteria In Solid Tumors (RECIST) response rate was 45%, median progression-free survival (PFS) was 6.4 months, and overall survival (OS) was 10.6 months. Platinum-resistant patients had better outcomes than did platinum-refractory patients (response rate, 54% vs 0%, P = 0.047; PFS 7.2 vs 1.8 months, P < 0.0001; OS 14.4 vs 3 months, P < 0.001). In regression models, time to progression after first-line treatment and platinum-refractory status were the strongest predictors of response and PFS or OS, respectively. Patients with time to progression after first-line treatment longer than 3 months showed PFS and OS of 7.9 and 14.7 months, respectively. Toxicity was manageable, with only 13% of cycles administered at reduced doses. Conclusions Epirubicin, cisplatin, and capecitabine seems to be active in platinum-resistant relapsed EOC with manageable toxicity. Further prospective investigation of platinum-anthracycline combinations is warranted in patients who relapse 3 to 6 months after

  11. Novel platinum black electroplating technique improving mechanical stability.

    PubMed

    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.

  12. Inhibition of nuclear factor kappaB proteins-platinated DNA interactions correlates with cytotoxic effectiveness of the platinum complexes

    PubMed Central

    Brabec, Viktor; Kasparkova, Jana; Kostrhunova, Hana; Farrell, Nicholas P.

    2016-01-01

    Nuclear DNA is the target responsible for anticancer activity of platinum anticancer drugs. Their activity is mediated by altered signals related to programmed cell death and the activation of various signaling pathways. An example is activation of nuclear factor kappaB (NF-κB). Binding of NF-κB proteins to their consensus sequences in DNA (κB sites) is the key biochemical activity responsible for the biological functions of NF-κB. Using gel-mobility-shift assays and surface plasmon resonance spectroscopy we examined the interactions of NF-κB proteins with oligodeoxyribonucleotide duplexes containing κB site damaged by DNA adducts of three platinum complexes. These complexes markedly differed in their toxic effects in tumor cells and comprised highly cytotoxic trinuclear platinum(II) complex BBR3464, less cytotoxic conventional cisplatin and ineffective transplatin. The results indicate that structurally different DNA adducts of these platinum complexes exhibit a different efficiency to affect the affinity of the platinated DNA (κB sites) to NF-κB proteins. Our results support the hypothesis that structural perturbations induced in DNA by platinum(II) complexes correlate with their higher efficiency to inhibit binding of NF-κB proteins to their κB sites and cytotoxicity as well. However, the full generalization of this hypothesis will require to evaluate a larger series of platinum(II) complexes. PMID:27574114

  13. Overcoming Platinum Resistance in Ovarian Carcinoma

    PubMed Central

    Matsuo, Koji; Lin, Yvonne G.; Roman, Lynda D.; Sood, Anil K.

    2010-01-01

    Importance of the field Ovarian cancer remains a deadly malignancy because most patients develop recurrent disease that is resistant to chemotherapy, including platinum. Because response rates for current treatment regimens are relatively similar and unfortunately low, no standard chemotherapy for platinum-resistant ovarian cancer exists. Areas covered in this review A systematic literature review of clinical studies published between January 2005 and March 2010 was conducted using search engines, PubMed and MEDLINE with the entry keywords, ovarian cancer and platinum resistance. This search revealed 40 clinical trials (1793 patients). What the reader will gain Gemcitabine was the most common drug used in clinical trials reporting higher response rates, ≥+1 SD of overall response rate (5 out of 8). Gemcitabine-based combination therapy showed an average response rate of 27.2% (95%CI 22.4–32.0). Combination of gemcitabine and pegylated liposomal doxorubicin (PLD) was the most common regimen (n=3) and was associated with possible additive effects in platinum-resistant ovarian cancer patients: response rate, gemcitabine alone 6.1%, PLD alone 19.8%, and gemcitabine with PLD 28.7% (95%CI 20.4–37.0), respectively. Take home message Analysis of recent clinical trials showed that gemcitabine-based combination chemotherapy was associated with the highest anti-tumor effects in platinum-resistant ovarian cancer patients during the study period. PMID:20815774

  14. Association of a Platinum Complex to a G-Quadruplex Ligand Enhances Telomere Disruption.

    PubMed

    Charif, Razan; Granotier-Beckers, Christine; Bertrand, Hélène Charlotte; Poupon, Joël; Ségal-Bendirdjian, Evelyne; Teulade-Fichou, Marie-Paule; Boussin, François D; Bombard, Sophie

    2017-08-21

    Telomeres protect the ends of chromosomes against illegitimate recombination and repair. They can be targets for G-quadruplex ligands and platinum complexes due to their repeated G-rich sequences. Protection of telomeres is ensured by a complex of six proteins, including TRF2, which inhibits the DNA damage response pathway. We analyzed telomere modifications induced in cancer cells by the experimental hybrid platinum complex, Pt-MPQ, comprising both an ethylene diamine monofunctional platinum complex and a G-quadruplex recognition moiety (MPQ). Pt-MPQ promotes the displacement of two telomeric proteins (TRF2 and TRF1) from telomeres, as well as the formation of telomere damage and telomere sister losses, whereas the control compound MPQ does not. This suggests that the platinum moiety potentiates the targeting of the G-quadruplex ligand to telomeres, opening a new perspective for telomere biology and anticancer therapy. Interestingly, the chemotherapy drug cisplatin, which has no specific affinity for G-quadruplex structures, partially induces the TRF2 delocalization from telomeres but produces less telomeric DNA damage, suggesting that this TRF2 displacement could be independent of G-quadruplex recognition.

  15. Platinum(II)-Oligonucleotide Coordination Based Aptasensor for Simple and Selective Detection of Platinum Compounds.

    PubMed

    Cai, Sheng; Tian, Xueke; Sun, Lianli; Hu, Haihong; Zheng, Shirui; Jiang, Huidi; Yu, Lushan; Zeng, Su

    2015-10-20

    Wide use of platinum-based chemotherapeutic regimens for the treatment for carcinoma calls for a simple and selective detection of platinum compound in biological samples. On the basis of the platinum(II)-base pair coordination, a novel type of aptameric platform for platinum detection has been introduced. This chemiluminescence (CL) aptasensor consists of a designed streptavidin (SA) aptamer sequence in which several base pairs were replaced by G-G mismatches. Only in the presence of platinum, coordination occurs between the platinum and G-G base pairs as opposed to the hydrogen-bonded G-C base pairs, which leads to SA aptamer sequence activation, resulting in their binding to SA coated magnetic beads. These Pt-DNA coordination events were monitored by a simple and direct luminol-peroxide CL reaction through horseradish peroxidase (HRP) catalysis with a strong chemiluminescence emission. The validated ranges of quantification were 0.12-240 μM with a limit of detection of 60 nM and selectivity over other metal ions. This assay was also successfully used in urine sample determination. It will be a promising candidate for the detection of platinum in biomedical and environmental samples.

  16. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer.

    PubMed

    Mirza, Mansoor R; Monk, Bradley J; Herrstedt, Jørn; Oza, Amit M; Mahner, Sven; Redondo, Andrés; Fabbro, Michel; Ledermann, Jonathan A; Lorusso, Domenica; Vergote, Ignace; Ben-Baruch, Noa E; Marth, Christian; Mądry, Radosław; Christensen, René D; Berek, Jonathan S; Dørum, Anne; Tinker, Anna V; du Bois, Andreas; González-Martín, Antonio; Follana, Philippe; Benigno, Benedict; Rosenberg, Per; Gilbert, Lucy; Rimel, Bobbie J; Buscema, Joseph; Balser, John P; Agarwal, Shefali; Matulonis, Ursula A

    2016-12-01

    Niraparib is an oral poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) 1/2 inhibitor that has shown clinical activity in patients with ovarian cancer. We sought to evaluate the efficacy of niraparib versus placebo as maintenance treatment for patients with platinum-sensitive, recurrent ovarian cancer. In this randomized, double-blind, phase 3 trial, patients were categorized according to the presence or absence of a germline BRCA mutation (gBRCA cohort and non-gBRCA cohort) and the type of non-gBRCA mutation and were randomly assigned in a 2:1 ratio to receive niraparib (300 mg) or placebo once daily. The primary end point was progression-free survival. Of 553 enrolled patients, 203 were in the gBRCA cohort (with 138 assigned to niraparib and 65 to placebo), and 350 patients were in the non-gBRCA cohort (with 234 assigned to niraparib and 116 to placebo). Patients in the niraparib group had a significantly longer median duration of progression-free survival than did those in the placebo group, including 21.0 vs. 5.5 months in the gBRCA cohort (hazard ratio, 0.27; 95% confidence interval [CI], 0.17 to 0.41), as compared with 12.9 months vs. 3.8 months in the non-gBRCA cohort for patients who had tumors with homologous recombination deficiency (HRD) (hazard ratio, 0.38; 95% CI, 0.24 to 0.59) and 9.3 months vs. 3.9 months in the overall non-gBRCA cohort (hazard ratio, 0.45; 95% CI, 0.34 to 0.61; P<0.001 for all three comparisons). The most common grade 3 or 4 adverse events that were reported in the niraparib group were thrombocytopenia (in 33.8%), anemia (in 25.3%), and neutropenia (in 19.6%), which were managed with dose modifications. Among patients with platinum-sensitive, recurrent ovarian cancer, the median duration of progression-free survival was significantly longer among those receiving niraparib than among those receiving placebo, regardless of the presence or absence of gBRCA mutations or HRD status, with moderate bone marrow toxicity. (Funded by

  17. Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance

    PubMed Central

    Nagaraj, Anil Belur; Joseph, Peronne; Kovalenko, Olga; Singh, Sareena; Armstrong, Amy; Redline, Raymond; Resnick, Kimberly; Zanotti, Kristine; Waggoner, Steven; DiFeo, Analisa

    2015-01-01

    Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/β-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/β-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/β-catenin signaling is activated in ovarian CICs, and targeted inhibition of β-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/β-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/β-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option. PMID:26125441

  18. Critical role of Wnt/β-catenin signaling in driving epithelial ovarian cancer platinum resistance.

    PubMed

    Nagaraj, Anil Belur; Joseph, Peronne; Kovalenko, Olga; Singh, Sareena; Armstrong, Amy; Redline, Raymond; Resnick, Kimberly; Zanotti, Kristine; Waggoner, Steven; DiFeo, Analisa

    2015-09-15

    Resistance to platinum-based chemotherapy is the major barrier to treating epithelial ovarian cancer. To improve patient outcomes, it is critical to identify the underlying mechanisms that promote platinum resistance. Emerging evidence supports the concept that platinum-based therapies are able to eliminate the bulk of differentiated cancer cells, but are unable to eliminate cancer initiating cells (CIC). To date, the relevant pathways that regulate ovarian CICs remain elusive. Several correlative studies have shown that Wnt/β-catenin pathway activation is associated with poor outcomes in patients with high-grade serous ovarian cancer (HGSOC). However, the functional relevance of these findings remain to be delineated. We have uncovered that Wnt/β-catenin pathway activation is a critical driver of HGSOC chemotherapy resistance, and targeted inhibition of this pathway, which eliminates CICs, represents a novel and effective treatment for chemoresistant HGSOC. Here we show that Wnt/β-catenin signaling is activated in ovarian CICs, and targeted inhibition of β-catenin potently sensitized cells to cisplatin and decreased CIC tumor sphere formation. Furthermore, the Wnt/β-catenin specific inhibitor iCG-001 potently sensitized cells to cisplatin and decreased stem-cell frequency in platinum resistant cells. Taken together, our data is the first report providing evidence that the Wnt/β-catenin signaling pathway maintains stem-like properties and drug resistance of primary HGSOC PDX derived platinum resistant models, and therapeutic targeting of this pathway with iCG-001/PRI-724, which has been shown to be well tolerated in Phase I trials, may be an effective treatment option.

  19. The efficacy and safety of platinum plus gemcitabine (PG) chemotherapy with or without molecular targeted agent (MTA) in first-line treatment of non-small cell lung cancer (NSCLC)

    PubMed Central

    Yang, Jiaying; He, Jieyu; Yu, Miao; Li, Taishun; Luo, Li; Liu, Pei

    2016-01-01

    Abstract Background: Trials investigating the efficacy and safety of combining molecular targeted agent (MTA) with platinum–gemcitabine (PG) in first-line treatment of advanced non-small cell lung cancer (NSCLC) have shown inconsistent findings. This meta-analysis aimed to explore whether the addition of MTAs to PG in NSCLC could provide a survival benefit with a tolerable toxicity. Methods: Web of knowledge, PubMed, Ovid, Embase, and Cochrane Library were searched to identify relevant studies and extract data on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and common grade 3 or 4 adverse events. Subgroup analyses were conducted on the basis of race and the type of MTA. Results: Twelve trials with a total of 6143 patients were included in this meta-analysis. Compared with PG chemotherapy, combination therapy of MTA with PG did not improve OS (hazard ratio [HR] = 0.96, 95% confidence interval [CI] = 0.90–1.01) but improved PFS (HR = 0.77, 95% CI = 0.66–0.89) and ORR (risk ratio [RR] = 1.33, 95% CI = 1.11–1.60). Subanalysis indicated that there was more incidence of grade 3 or 4 rash (RR = 11.20, 95% CI = 6.07–20.68), anemia (RR = 1.21, 95% CI = 1.01–1.46), diarrhea (RR = 2.62, 95% CI = 1.21–5.65), and anorexia (RR = 2.08, 95% CI = 1.12–3.88) in combining epidermal growth factor receptor targeted therapy group compared to PG group. An increased risk of grade 3 or 4 rash (RR = 5.08, 95% CI = 1.53–16.79), thrombocytopenia (RR = 1.50, 95% CI = 1.03–2.18), and hypertension (RR = 2.36, 95% CI = 1.05–5.32) was observed in sorafenib combination group. Conclusion: The combination of PG plus MTA was superior to PG alone in terms of PFS and ORR but not in OS. The combination chemotherapy also showed a higher frequency of grade 3 or higher toxic effects in patients with advanced NSCLC than PG chemotherapy. PMID:27977596

  20. Platinum Publications, March 1–March 30, 2017 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  1. Platinum Publications, October 30 – November 26, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  2. Platinum Publications, July 31–September 30, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  3. Platinum Publications as of December 3, 2013 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  4. Mineral resource of the month: platinum-group metals

    USGS Publications Warehouse

    Hilliard, Henry

    2003-01-01

    The precious metals commonly referred to as platinum-group metals (PGM) include iridium, osmium, palladium, platinum, rhodium and ruthenium. PGM are among the rarest of elements, and their market values — particularly for palladium, platinum and rhodium — are the highest of all precious metals.

  5. Platinum Publications, January 26–February 28, 2017 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  6. Platinum Publications, January 1–March 31, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  7. Platinum Publications, March 27 – April 30, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  8. Platinum Publications, May 1 – June 25, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  9. Platinum Publications, July 29–September 29, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  10. Platinum Publications, November 27, 2014 – February 26, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  11. Platinum Publications, October 28–November 30, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  12. Platinum Publications, June 26–July 30, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  13. Platinum Publications, April 28–May 31, 2017 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  14. Platinum Publications, June 1–June 30, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  15. Platinum Publications, January 1–March 31, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  16. Platinum Publications as of April 30, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  17. Platinum Publications, November 27, 2014 – February 26, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  18. Platinum Publications as of May 29, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  19. Platinum Publications as of September 25, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  20. Platinum Publications, February 27 – March 26, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  1. Platinum Publications, July 29–September 29, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  2. Platinum Publications as of April 30, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  3. Platinum Publications as of June 25, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  4. Platinum Publications as of September 25, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  5. Platinum Publications, July 1–July 28, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  6. Platinum Publications as of June 25, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  7. Platinum Publications, June 1–June 29, 2017 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  8. Platinum Publications as of December 3, 2013 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  9. Platinum Publications, October 1–29, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  10. Platinum Publications, June 30–July 26, 2017 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  11. Platinum Publications, July 26–August 30, 2017 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  12. Platinum Publications, September 30–October 27, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  13. Platinum Publications, October 30 – November 26, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  14. Platinum Publications, September 26 – October 29, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  15. Platinum Publications, February 27 – March 26, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  16. Platinum Publications, May 1 – June 25, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  17. Platinum Publications as of May 29, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  18. Platinum Publications, September 30–October 27, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  19. Platinum Publications, October 28–November 30, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  20. Platinum Publications, March 31–April 27, 2017 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  1. Platinum Publications as of March 6, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  2. Platinum Publications, March 27 – April 30, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  3. Platinum Publications, October 30–December 31, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  4. Platinum Publications, September 26 – October 29, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  5. Platinum Publications, June 1–June 30, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  6. Platinum Publications, June 26–July 30, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  7. Platinum Publications as of March 6, 2014 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 21 prestigious science journals. This list represents new publications generated from PubMed as of the date shown above. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  8. Platinum Publications, July 31–September 30, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  9. Platinum Publications, October 30–December 31, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  10. Platinum Publications, July 1–July 28, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  11. Platinum Publications, October 1–29, 2015 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected by Dr. Craig Reynolds, associate director, National Cancer Institute, from among the most recently published Platinum Publications.

  12. Platinum Publications, December 1–December 29, 2016 | Poster

    Cancer.gov

    Platinum Publications are selected from articles by NCI at Frederick scientists published in 42 prestigious science journals. This list represents articles published during the time period shown above, as generated from PubMed. Articles designated as Platinum Highlights are noteworthy articles selected from among the most recently published Platinum Publications.

  13. Surface decorated platinum carbonyl clusters

    NASA Astrophysics Data System (ADS)

    Ciabatti, Iacopo; Femoni, Cristina; Iapalucci, Maria Carmela; Longoni, Giuliano; Zacchini, Stefano; Zarra, Salvatore

    2012-06-01

    Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters.Four molecular Pt-carbonyl clusters decorated by Cd-Br fragments, i.e., [Pt13(CO)12{Cd5(μ-Br)5Br2(dmf)3}2]2- (1), [Pt19(CO)17{Cd5(μ-Br)5Br3(Me2CO)2}{Cd5(μ-Br)5Br(Me2CO)4}]2- (2), [H2Pt26(CO)20(CdBr)12]8- (3) and [H4Pt26(CO)20(CdBr)12(PtBr)x]6- (4) (x = 0-2), have been obtained from the reactions between [Pt3n(CO)6n]2- (n = 2-6) and CdBr2.H2O in dmf at 120 °C. The structures of these molecular clusters with diameters of 1.5-2 nm have been determined by X-ray crystallography. Both 1 and 2 are composed of icosahedral or bis-icosahedral Pt-CO cores decorated on the surface by Cd-Br motifs, whereas 3 and 4 display a cubic close packed Pt26Cd12 metal frame decorated by CO and Br ligands. An oversimplified and unifying approach to interpret the electron count of these surface decorated platinum carbonyl clusters is suggested, and extended to other low-valent organometallic clusters and Au-thiolate nanoclusters. CCDC 867747 and 867748. For crystallographic data in CIF or other electronic format see DOI: 10.1039/c2nr30400g

  14. Autonomous movement of platinum-loaded stomatocytes

    NASA Astrophysics Data System (ADS)

    Wilson, Daniela A.; Nolte, Roeland J. M.; van Hest, Jan C. M.

    2012-04-01

    Polymer stomatocytes are bowl-shaped structures of nanosize dimensions formed by the controlled deformation of polymer vesicles. The stable nanocavity and strict control of the opening are ideal for the physical entrapment of nanoparticles which, when catalytically active, can turn the stomatocyte morphology into a nanoreactor. Herein we report an approach to generate autonomous movement of the polymer stomatocytes by selectively entrapping catalytically active platinum nanoparticles within their nanocavities and subsequently using catalysis as a driving force for movement. Hydrogen peroxide is free to access the inner stomatocyte cavity, where it is decomposed by the active catalyst (the entrapped platinum nanoparticles) into oxygen and water. This generates a rapid discharge, which induces thrust and directional movement. The design of the platinum-loaded stomatocytes resembles a miniature monopropellant rocket engine, in which the controlled opening of the stomatocytes directs the expulsion of the decomposition products away from the reaction chamber (inner stomatocyte cavity).

  15. Chiral discrimination in platinum anticancer drugs.

    PubMed Central

    Benedetti, Michele; Malina, Jaroslav; Kasparkova, Jana; Brabec, Viktor; Natile, Giovanni

    2002-01-01

    In this article we review the biological activity of analogs of the antitumor drug cisplatin that contain chiral amine ligands. Interaction with DNA and formation of cross-links with adjacent purine bases are considered to be the crucial steps in the antitumor activity of this class of complexes. Because double-helical DNA has a chiral structure, interaction with enantiomeric complexes of platinum should lead to diastereomeric adducts. It has been demonstrated that DNA cross-links of platinum complexes with enantiomeric amine ligands not only can exhibit different conformational features but also can be processed differently by the cellular machinery as a consequence of these conformational differences. These results expand the general knowledge of how the stereochemistry of the platinum-DNA adduct can influence the cell response and contribute to understanding the processes that are crucial for antitumor activity. The steric requirements of the chiral ligands, in terms of configuration and flexibility, are also elucidated. PMID:12426131

  16. Autonomous movement of platinum-loaded stomatocytes.

    PubMed

    Wilson, Daniela A; Nolte, Roeland J M; van Hest, Jan C M

    2012-02-26

    Polymer stomatocytes are bowl-shaped structures of nanosize dimensions formed by the controlled deformation of polymer vesicles. The stable nanocavity and strict control of the opening are ideal for the physical entrapment of nanoparticles which, when catalytically active, can turn the stomatocyte morphology into a nanoreactor. Herein we report an approach to generate autonomous movement of the polymer stomatocytes by selectively entrapping catalytically active platinum nanoparticles within their nanocavities and subsequently using catalysis as a driving force for movement. Hydrogen peroxide is free to access the inner stomatocyte cavity, where it is decomposed by the active catalyst (the entrapped platinum nanoparticles) into oxygen and water. This generates a rapid discharge, which induces thrust and directional movement. The design of the platinum-loaded stomatocytes resembles a miniature monopropellant rocket engine, in which the controlled opening of the stomatocytes directs the expulsion of the decomposition products away from the reaction chamber (inner stomatocyte cavity).

  17. Extending the platinum-free interval with a non-platinum therapy in platinum-sensitive recurrent ovarian cancer. Results from the SOCRATES Retrospective Study.

    PubMed

    Pignata, Sandro; Ferrandina, Gabriella; Scarfone, Giovanna; Scollo, Paolo; Odicino, Franco; Selvaggi, Luigi; Katsaros, Dionyssios; Frigerio, Luigi; Mereu, Liliana; Ghezzi, Fabio; Manzione, Luigi; Lauria, Rossella; Breda, Enrico; Marforio, Giovanna; Ballardini, Michela; Lombardi, Alessandra Vernaglia; Sorio, Roberto; Tumolo, Salvatore; Costa, Bruno; Magni, Giovanna; Perrone, Francesco; Favalli, Giuseppe

    2006-01-01

    It has been proposed that extending the platinum-free interval with intervening non-platinum therapy increases the efficacy of a later re-treatment with platinum in platinum-sensitive recurrent ovarian cancer. This hypothesis is based on data from small series and although it has not been validated prospectively, this strategy has entered general practice in Italy in the last years. The SOCRATES study retrospectively assessed the pattern of care of a cohort of patients with recurrent platinum-sensitive ovarian cancer observed in the years 2000-2002 in 37 Italian centres. Data were collected between April and September 2005. Patients with recurrent ovarian cancer with a platinum-free interval >6 months were eligible. 493 patient files were collected and 428 were eligible and analyzed. The interval from the end of the 1st line to relapse was 6-12 months in 164 patients (39.5%) and >12 months in 251 cases (60.5%). Patients received a 2nd (100%), 3rd (80.1%), 4th (50.2%), 5th (28.3%), and 6th (11.9%) line of chemotherapy. At 2nd line 282 (65.9%) received platinum (group A), while 146 (34.1%) received non-platinum chemotherapy (group B). In the latter group, 67 patients received platinum at later progression (group B1), while 79 never received platinum (group B2). Median time to platinum re-treatment was 20 and 23.1 months in patients of groups A and B1, respectively. The response rate to the first platinum received was 74.4 and 57.4% in groups A and B1, respectively (p = 0.02). Group B2 was characterized by the worst response rate and survival. At multivariate analysis time of first platinum re-treatment (2nd line vs. later; p = 0.0132; OR = 2.34) and age (p = 0.0029; OR = 2.41) was independently associated with a higher possibility of response to platinum. With the limits of a retrospective study, our data question the hypothesis that extending the platinum-free interval with an intervening non-platinum therapy in patients with recurrent platinum-sensitive ovarian

  18. Coadsorbed H and CO interaction on platinum.

    PubMed

    Roman, Tanglaw; Nakanishi, Hiroshi; Kasai, Hideaki

    2008-10-21

    The behavior of hydrogen near a platinum-surface-adsorbed carbon monoxide molecule is described using a potential energy term constructed from density functional theory. A clear nonattractive interaction of hydrogen with CO is confirmed, most notably with oxygen, which retains its strong H-repulsive traits in the Pt-bound CO case. Inhibiting effects of CO greater than what is expected from simple adsorption site exclusion are discussed with regard to adsorption/desorption and mobility on platinum, as well as possibilities of COH and HCO formation.

  19. Recent Advances in Platinum (IV) Complex-Based Delivery Systems to Improve Platinum (II) Anticancer Therapy.

    PubMed

    Han, Xiaopeng; Sun, Jin; Wang, Yongjun; He, Zhonggui

    2015-11-01

    Cisplatin and its platinum (Pt) (II) derivatives play a key role in the fight against various human cancers such as testicular, ovarian, head and neck, lung tumors. However, their application in clinic is limited due to dose- dependent toxicities and acquired drug resistances, which have prompted extensive research effort toward the development of more effective Pt (II) delivery strategies. The synthesis of Pt (IV) complex is one such an area of intense research fields, which involves their in vivo conversion into active Pt (II) molecules under the reducing intracellular environment, and has demonstrated encouraging preclinical and clinical outcomes. Compared with Pt (II) complexes, Pt (IV) complexes not only exhibit an increased stability and reduced side effects, but also facilitate the intravenous-to-oral switch in cancer chemotherapy. The overview briefly analyzes statuses of Pt (II) complex that are in clinical use, and then focuses on the development of Pt (IV) complexes. Finally, recent advances in Pt (IV) complexes in combination with nanocarriers are highlighted, addressing the shortcomings of Pt (IV) complexes, such as their instability in blood and irreversibly binding to plasma proteins and nonspecific distribution, and taking advantage of passive and active targeting effect to improve Pt (II) anticancer therapy. © 2015 Wiley Periodicals, Inc.

  20. Nonuniformity effects in a hybrid platinum silicide imaging device

    NASA Astrophysics Data System (ADS)

    Dereniak, E. L.; Perry, D. L.

    1991-09-01

    The objective of this project was twofold. The first objective was to characterize the Hughes Aircraft Company CRC-365 platinum silicide imaging device in a staring infrared sensor system. The CRC-365 is a hybrid 256 x 256 IR focal plane array that operates in the 3-5 micrometer thermal infrared band. A complete sensor and computer interface were built for these tests, using plans provided by the Rome Laboratory at Hanscom Air Force Base, Massachusetts. Testing of the device revealed largely satisfactory performance, with notable exceptions in the areas of temporal response, temporal noise, and electrical crosstalk. The second objective of this research was to advance the understanding of how detector nonuniformity effects reduce the performance of sensors of this type. Notable accomplishments in this included a complete linear analysis of corrected thermal imaging in platinum silicide sensors, a nonlinear analysis of the CRC-365s expected performance, analysis of its actual performance when operated with nonuniformity correction, and the development of a new figure of merit. It was demonstrated that the CRC-365 is capable of maintaining background-noise-limited performance over at least a 40 K target temperature range, when operated with two-point nonuniformity correction.

  1. Nonuniformity effects in a hybrid platinum silicide imaging device

    NASA Astrophysics Data System (ADS)

    Dereniak, Eustace L.; Perry, David L.

    1992-05-01

    The objective of this project was twofold. The first objective was to characterize the Hughes Aircraft Company CRC-365 platinum silicide imaging device in a starting infrared sensor system. The CRC-365 is a hybrid 256 x 256 IR focal plane array that operates in the 3-5 micrometer thermal infrared band. A complete sensor and computer interface were built for these tests, using, plans provided by the Rome Laboratory at Hanscom AFB. Testing of the device revealed largely satisfactory performance, with notable exception in the areas of temporal response, temporal noise, and electrical crosstalk. The second objective of this research was to advance the understanding of how detector nonuniformity effects reduce the performance of sensors of this type. Notable accomplishments in this area included a complete linear analysis of corrected thermal imaging in platinum silicide sensors, a nonlinear analysis of the CRC-365's expected performance, analysis of its actual performance when operated with nonuniformity correction, and the development of a new figure of merit. It was demonstrated that the CRC-365 is capable of maintaining background-noise-limited performance over at least a 40 K target temperature range, when operated with two-point nonuniformity correction.

  2. Quantitative skin prick and bronchial provocation tests with platinum salt.

    PubMed Central

    Merget, R; Schultze-Werninghaus, G; Bode, F; Bergmann, E M; Zachgo, W; Meier-Sydow, J

    1991-01-01

    Occupational asthma due to platinum salts is a frequent disease in platinum refineries. The diagnosis is based upon a history of work related symptoms and a positive skin prick test with platinum salts. Bronchial provocation tests have not been performed in epidemiological studies because the skin test is believed to be highly specific and sensitive. As no reliable data about this issue currently exist, this study assesses the use of skin prick and bronchial provocation tests with methacholine and platinum salt in platinum refinery workers. Twenty seven of 35 workers, who were referred to our clinic with work related symptoms and nine control subjects with bronchial hyperreactivity underwent a skin prick test and bronchial provocation with methacholine and platinum salt. For skin prick and bronchial provocation tests with platinum salt a 10(-2)-10(-8) mol/l hexachloroplatinic acid solution, in 10-fold dilutions was used. Four of the 27 subjects and all controls showed neither a bronchial reaction nor a skin reaction. Twenty three subjects were considered allergic to platinum salt; 22 of these showed a fall of 50% or more in specific airway conductance after inhalation of the platinum salt solution. Four workers experienced a positive bronchial reaction despite a negative skin prick test. No correlation of responsiveness to methacholine with responsiveness to platinum salt was found, but the skin prick test correlated with the bronchial reaction to platinum salt (rs = 0.50, p less than 0.023, n = 22). One dual reaction was seen in bronchial provocation tests. Side effects of both skin tests and bronchial provocation tests with platinum salt were rare and were not encountered in workers without a skin reaction to platinum salt. It is concluded that bronchial provocation tests with platinum salts should be performed on workers with work related symptoms but negative skin tests with platinum salts. PMID:1772797

  3. Inhibition of Notch Signaling in Combination with Paclitaxel Reduces Platinum-Resistant Ovarian Tumor Growth

    PubMed Central

    Groeneweg, Jolijn W.; DiGloria, Celeste M.; Yuan, Jing; Richardson, William S.; Growdon, Whitfield B.; Sathyanarayanan, Sriram; Foster, Rosemary; Rueda, Bo R.

    2014-01-01

    Introduction: Ovarian cancer (OvCa) is the most lethal gynecologic malignancy in the United States because of chemoresistant recurrent disease. Our objective was to investigate the efficacy of inhibiting the Notch pathway with a γ-secretase inhibitor (GSI) in an OvCa patient-derived xenograft model as a single agent therapy and in combination with standard chemotherapy. Methods: Immunocompromised mice bearing xenografts derived from clinically platinum-sensitive human ovarian serous carcinomas were treated with vehicle, GSI (MRK-003) alone, paclitaxel and carboplatin (P/C) alone, or the combination of GSI and P/C. Mice bearing platinum-resistant xenografts were given GSI with or without paclitaxel. Gene transcript levels of the Notch pathway target Hes1 were analyzed using RT-PCR. Notch1 and Notch3 protein levels were evaluated. The Wilcoxon rank-sum test was used to assess significance between the different treatment groups. Results: Expression of Notch1 and 3 was variable. GSI alone decreased tumor growth in two of three platinum-sensitive ovarian tumors (p < 0.05), as well as in one of three platinum-sensitive tumors (p = 0.04). The combination of GSI and paclitaxel was significantly more effective than GSI alone and paclitaxel alone in all platinum-resistant ovarian tumors (all p < 0.05). The addition of GSI did not alter the effect of P/C in platinum-sensitive tumors. Interestingly, although the response of each tumor to chronic GSI exposure did not correlate with its endogenous level of Notch expression, GSI did negatively affect Notch signaling in an acute setting. Conclusion: Inhibiting the Notch signaling cascade with a GSI reduces primary human xenograft growth in vivo. GSI synergized with conventional cytotoxic chemotherapy only in the platinum-resistant OvCa models with single agent paclitaxel. These findings suggest inhibition of the Notch pathway in concert with taxane therapy may hold promise for treatment of platinum-resistant Ov

  4. Acalabrutinib (ACP-196) in Relapsed Chronic Lymphocytic Leukemia

    PubMed Central

    Byrd, John C; Harrington, Bonnie; O’Brien, Susan; Jones, Jeffrey A; Schuh, Anna; Devereux, Steve; Chaves, Jorge; Wierda, William G; Awan, Farrukh T; Brown, Jennifer R; Hillmen, Peter; Stephens, Deborah M; Ghia, Paolo; Barrientos, Jacqueline C; Pagel, John M; Woyach, Jennifer; Johnson, Dave; Huang, Jane; Wang, Xiaolin; Lannutti, Brian J; Covey, Todd; Fardis, Maria; McGreivy, Jesse; Hamdy, Ahmed; Rothbaum, Wayne; Izumi, Raquel; Diacovo, Thomas G; Johnson, Amy J; Furman, Richard R

    2016-01-01

    Background Irreversible inhibition of Bruton tyrosine kinase (Btk) by ibrutinib represents a significant therapeutic advance for chronic lymphocytic leukemia (CLL). However, ibrutinib also irreversibly inhibits alternative kinase targets, which potentially compromise its therapeutic index. Acalabrutinib (ACP-196) is a more selective irreversible Btk inhibitor specifically designed to improve upon the safety and efficacy of first generation Btk inhibitors. Methods Sixty-one patients with relapsed CLL were treated in a phase 1–2 multicenter study designed to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of oral acalabrutinib. Patients were continuously treated with acalabrutinib 100 to 400 mg once daily in the dose-escalation portion of the study, and 100 mg twice daily in the expansion portion. Results Patient demographics include a median age of 62 years; median of 3 prior therapies; 31% del(17)(p13.1) and 75% unmutated immunoglobulin heavy chain variable genes. No dose-limiting toxicities occurred. The most common adverse events observed were headache (43%), diarrhea (39%) and increased weight (26%). Most adverse events were Grade 1–2. At a median follow-up of 14.3 months, the best overall response rate was 95%, including 85% partial response, 10% partial response with lymphocytosis and 5% stable disease. In patients with del(17)(p13.1), the best overall response was 100%. No cases of Richter’s transformation and only 1 CLL progression have occurred. Conclusions Acalabrutinib is a highly selective Btk inhibitor that provides effective and well tolerated treatment for patients with relapsed CLL, including those with del(17)(p13.1). PMID:26641137

  5. Use of platinum electrodes for the electrochemical detection of bacteria

    NASA Technical Reports Server (NTRS)

    Wilkins, J. R.

    1978-01-01

    Platinum electrodes with surface area ratios of four to one were used to detect and enumerate a variety of gram-positive and gram-negative organisms. Linear relationships were established between inoculum size and detection time. End points for platinum electrodes were similar to those obtained with a platinum-reference electrode combination. Shape of the overall response curves and length of detection times for gram-positive organisms were markedly different than those for the majority of gram-negative species. Platinum electrodes are better than the platinum-reference electrode combination because of cost, ease of handling, and clearer definition of the end point.

  6. Platinum recycling in the United States in 1998

    USGS Publications Warehouse

    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.

  7. Use of platinum electrodes for the electrochemical detection of bacteria

    NASA Technical Reports Server (NTRS)

    Wilkins, J. R.

    1978-01-01

    Platinum electrodes with surface area ratios of four to one were used to detect and enumerate a variety of gram-positive and gram-negative organisms. Linear relationships were established between inoculum size and detection time. End points for platinum electrodes were similar to those obtained with a platinum-reference electrode combination. Shape of the overall response curves and length of detection times for gram-positive organisms were markedly different than those for the majority of gram-negative species. Platinum electrodes are better than the platinum-reference electrode combination because of cost, ease of handling, and clearer definition of the end point.

  8. Outpatient desensitization in selected patients with platinum hypersensitivity reactions.

    PubMed

    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.

  9. Synthesis and characterization of new platinum(II) and platinum(IV) triphyrin complexes.

    PubMed

    Xue, Zhaoli; Kuzuhara, Daiki; Ikeda, Shinya; Okujima, Tetsuo; Mori, Shigeki; Uno, Hidemitsu; Yamada, Hiroko

    2013-02-18

    Metalation of 6,13,20,21-tetrakis(4-methylphenyl)-22H-tribenzo[14]triphyrin(2.1.1) with PtCl(2) gave a platinum(II) complex having a square-planar coordination structure with two pyrrolic nitrogen atoms and two chloride ions, with a saddle-shaped macrocycle. This platinum(II) complex was easily oxidized by air to an octahedral platinum(IV) complex coordinated by three pyrrolic nitrogen atoms as a tridentate monoanionic cyclic ligand and three chloride ions. When platinum(II) triphyrin was crystallized in air, an oxygen atom was incorporated between two α-carbon atoms of the pyrroles as an oxygen bridge to intercept the 14π aromatic system.

  10. miR-196b-5p Regulates Colorectal Cancer Cell Migration and Metastases through Interaction with HOXB7 and GALNT5.

    PubMed

    Stiegelbauer, Verena; Vychytilova-Faltejskova, Petra; Karbiener, Michael; Pehserl, Anna-Maria; Reicher, Andreas; Resel, Margit; Heitzer, Ellen; Ivan, Cristina; Bullock, Marc; Ling, Hui; Deutsch, Alexander; Wulf-Goldenberg, Annika; Adiprasito, Jan Basri; Stoeger, Herbert; Haybaeck, Johannes; Svoboda, Marek; Stotz, Michael; Hoefler, Gerald; Slaby, Ondrej; Calin, George Adrian; Gerger, Armin; Pichler, Martin

    2017-09-01

    Purpose: miR-196b-5p has been previously implicated in malignant transformation; however, its role in colorectal cancer has not been fully explored. In this study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in colorectal cancer.Experimental Design: miR-196b-5p expression was quantitated by qRT-PCR in 2 independent cohorts composed of 292 patients with colorectal cancer in total, to explore its biomarker potential. Transient and stable gain- and loss-of-function experiments were conducted in a panel of colorectal cancer cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemosensitivity, migration/invasion, and metastases formation in vitro and in vivo The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in silico target prediction tools, luciferase interaction assays, and phenocopy/rescue gene knockdown experiments.Results: Low miR-196b-5p expression was significantly associated with metastases and poor outcomes in 2 independent colorectal cancer patient cohorts (P < 0.05, log-rank test). miR-196b-5p inhibition led to significantly increased colorectal cancer cell migration/invasion and metastases formation in mice, whereas ectopic overexpression showed the opposite phenotype. Molecular profiling and target confirmation identified an interaction between miR-196b-5p and HOXB7 and GALNT5, which in turn regulated colorectal cancer cell migration.Conclusions: The association of low levels of miR-196b-5p and poor prognosis in patients with colorectal cancer can be explained by its influence on cancer cell migration and metastases formation. miR-196b-5p has an impact on colorectal cancer progression pathways through direct interaction with genes involved in cancer cell migration. Clin Cancer Res; 23(17); 5255-66. ©2017 AACR. ©2017 American Association for Cancer Research.

  11. Fraction of platinum surface covered with carbonaceous species following hydrogenolysis of hexane on platinum alumina catalysts

    SciTech Connect

    Rivera Latas, F.J.

    1986-01-01

    Catalytic naphtha reforming plays a major role in satisfying the demand for unleaded, high octane gasoline. Hydrogen containing carbonaceous deposits (coke) accumulation on the surface of the catalysts during reforming operation. This study investigated the following question: what is the fraction of the platinum surface covered with the deposits following a typical reforming reaction. These observations prompted us to prepare a platinum-alumina catalyst with a high metal content (5%) to enhance the sensitivity of experiments designed to examine the platinum surface following hexane hydrogenolysis. The reaction was selected because it is a good model reaction for catalytic reforming and it was also studied by the Somorjai group in the higher temperature range of their work. Hydrogenolysis of hexane was carried out in a flow system for 3 h at 713 K, at atmospheric pressure, and around 0.1 total conversion. The catalyst was cooled down to room temperature in the reactant mixture, and the fraction of surface platinum atoms exposed was measured in situ by four independent methods: titration of adsorbed oxygen by dihydrogen, chemisorption of carbon monoxide, infra-red spectroscopy of carbon monoxide bonded to platinum, and rate of ethylene hydrogenation. Independent gravimetric studies showed that coke deposits of around 1% by weight were formed on the same catalyst during hydrogenolysis of hexane under similar conditions. Each of the four methods indicate that approximately 50% of the platinum surface remains exposed under the conditions.

  12. Evaluation of industrial platinum resistance thermometers

    NASA Technical Reports Server (NTRS)

    Daryabeigi, Kamran; Dillontownes, Lawrence A.; Alderfer, David W.

    1987-01-01

    The calibration and stability of four surface temperature measuring industrial platinum resistance thermometers for use in the temperature range -120 C to 160 C was investigated. It was found that the calibration formulation of the International Practical Temperature Scale of 1968 provided the most accurate calibration. It was also found that all the resistance thermometers suffered from varying degrees of instability and hysteresis.

  13. Skin Sensitizing Potency of Halogenated Platinum Salts.

    EPA Science Inventory

    The relationship between occupational exposure to halogenated platinum (Pt) salts and Pt-specific allergic sensitization is well-established. Although human case reports and clinical studies demonstrate that Pt salts are potent skin sensitizers, no studies have been published tha...

  14. Skin Sensitizing Potency of Halogenated Platinum Salts.

    EPA Science Inventory

    The relationship between occupational exposure to halogenated platinum (Pt) salts and Pt-specific allergic sensitization is well-established. Although human case reports and clinical studies demonstrate that Pt salts are potent skin sensitizers, no studies have been published tha...

  15. On the enzymatic formation of platinum nanoparticles

    NASA Astrophysics Data System (ADS)

    Govender, Y.; Riddin, T. L.; Gericke, M.; Whiteley, C. G.

    2010-01-01

    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 °C, respectively, a half-life stability of 36 min and a V max and K m of 3.57 nmol min-1 mL-1 and 2.25 mM, respectively. This enzyme was inhibited (non-competitively) by hydrogen hexachloroplatinic acid (H2PtCl6) at 1 or 2 mM with a K i value of 118 μM. Incubation of the platinum salt with the pure enzyme under an atmosphere of hydrogen and optimum enzyme conditions (pH 7.5, 38 °C) afforded <10% bioreduction after 8 h while at conditions suitable for platinum nanoparticle formation (pH 9, 65 °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.

  16. Preparation of platinum modified titanium dioxide nanoparticles with the use of laser ablation in water.

    PubMed

    Siuzdak, K; Sawczak, M; Klein, M; Nowaczyk, G; Jurga, S; Cenian, A

    2014-08-07

    We report on the preparation method of nanocrystalline titanium dioxide modified with platinum by using nanosecond laser ablation in liquid (LAL). Titania in the form of anatase crystals has been prepared in a two-stage process. Initially, irradiation by laser beam of a titanium metal plate fixed in a glass container filled with deionized water was conducted. After that, the ablation process was continued, with the use of a platinum target placed in a freshly obtained titania colloid. In this work, characterization of the obtained nanoparticles, based on spectroscopic techniques--Raman, X-ray photoelectron and UV-vis reflectance spectroscopy--is given. High resolution transmission electron microscopy was used to describe particle morphology. On the basis of photocatalytic studies we observed the rate of degradation process of methylene blue (MB) (a model organic pollution) in the presence of Pt modified titania in comparison to pure TiO2--as a reference case. Physical and chemical mechanisms of the formation of platinum modified titania are also discussed here. Stable colloidal suspensions containing Pt modified titanium dioxide crystalline anatase particles show an almost perfect spherical shape with diameters ranging from 5 to 30 nm. The TiO2 nanoparticles decorated with platinum exhibit much higher (up to 30%) photocatalytic activity towards the degradation of MB under UV illumination than pure titania.

  17. Tobacco Mosaic Virus-Delivered Cisplatin Restores Efficacy in Platinum-Resistant Ovarian Cancer Cells.

    PubMed

    Franke, Christina E; Czapar, Anna E; Patel, Ravi B; Steinmetz, Nicole F

    2017-09-19

    Platinum resistance in ovarian cancer is the major determinant of disease prognosis. Resistance can first appear at the onset of disease or develop in response to platinum-based chemotherapy. Due to poor response to alternate chemotherapies and lack of targeted therapies, there is an urgent clinical need for a new avenue toward treatment of platinum-resistant (PR) ovarian cancer. Nanoscale delivery systems hold potential to overcome resistance mechanisms. In this work, we present tobacco mosaic virus (TMV) as a nanocarrier for cisplatin for treatment of PR ovarian cancer cells. The TMV-cisplatin conjugate (TMV-cisPt) was synthesized using a charge-driven reaction that, like a classic click reaction, is simple and reliable for large-scale production. Up to ∼1900 cisPt were loaded per TMV-cisPt with biphasic release profiles characterized by a fast half-life (t1) of ∼1 h and slow half-life (t2) of ∼12 h independent of pH. Efficient cell uptake of TMV was observed when incubated with ovarian cancer cells, and TMV-cisPt demonstrated superior cytotoxicity and DNA double strand breakage (DSB) in platinum-sensitive (PS) and PR cancer cells when compared to free cisplatin. The cytotoxicity in PR ovarian cancer cells and overall lower effective dosage requirement makes TMV-cisPt a powerful candidate for improved ovarian cancer treatment strategies.

  18. Platinum oxidation responsible for degradation of platinum-cobalt alloy cathode catalysts for polymer electrolyte fuel cells

    NASA Astrophysics Data System (ADS)

    Hidai, Shoichi; Kobayashi, Masaki; Niwa, Hideharu; Harada, Yoshihisa; Oshima, Masaharu; Nakamori, Yoji; Aoki, Tsutomu

    2012-10-01

    Platinum oxidation of Pt-Co alloy catalysts for polymer electrolyte fuel cells was investigated for a series of Pt-Co alloy catalysts with different specification. The chemical state of platinum evaluated by soft X-ray photoemission spectroscopy was compared with the electrochemical properties to elucidate the origin of catalyst degradation. Increase in the particle size of Pt-Co alloy catalysts caused the decrease in the concentration of platinum hydroxide and improved the catalyst durability. Applying potential cycling below 1.0 V, only platinum hydroxide was observed, while platinum oxides, PtO and PtO2, appeared after potential cycling up to 1.2 V. The peak shift of Pt 4f spectra after the potential cycling implies that these platinum hydroxide and oxide are dissolved and deposited on another platinum catalyst in a reduced metallic state, which causes the catalyst degradation.

  19. Platinum Group Metal Recycling Technology Development - Final Report

    SciTech Connect

    Lawrence Shore

    2009-08-19

    BASF Catalysts LLC, formerly Engelhard Corporation, has completed a project to recover Pt from PEM fuel cell membrane electrode assemblies. The project, which began in 2003, has met the project objective of an environmentally-friendly, cost-effective method for recovery of platinum without release of hydrogen fluoride. This has been achieved using a combination of milling, dispersion and acid leaching. 99% recovery of Pt was achieved, and this high yield can be scaled up using one vessel for a single leach and rinse. Leaching was been successfully achieved using a 10% solids level, double the original target. At this solids content, the reagent and utility costs represent ~0.35% of the Pt value of a lot, using very conservative assumptions. The main cost of the process is capital depreciation, followed by labor.

  20. RF magnetron sputtering of thick platinum coatings on glass microspheres

    SciTech Connect

    Meyer, S.F.; Hsieh, E.J.; Burt, R.J.

    1980-05-28

    Thick platinum coatings on glass microspheres are needed for proposed Laser Fusion targets. The spherical nature of these substrates coupled with the small dimensions (approx. 100 ..mu..m OD) make it difficult to achieve a smooth and uniform coating. Coating problems encountered include a rough surface and porous microstructure from the oblique incidence and lack of temperature and bias control, clumping of the microspheres causing non-uniformities, and particle accumulation causing cone defects. Sputtering parameters significantly affecting the coatings include total pressure, DC substrate bias, and the addition of doping gases. Using an ultrasonic vibrating screened cage and RF magnetron Sputtergun, we have successfully batch coated microspheres with up to 6 ..mu..m of Pt, with a surface roughness of 200 nm, thickness non-concentricity of 300 nm, and density greater than 98% of bulk Pt.

  1. Extension of activation cross section data of long lived products in deuteron induced nuclear reactions on platinum up to 50 MeV

    NASA Astrophysics Data System (ADS)

    Ditrói, F.; Tárkányi, F.; Takács, S.; Hermanne, A.

    2017-06-01

    In the frame of a systematical study of light ion induced nuclear reactions on platinum, activation cross sections for deuteron induced reactions were investigated. Excitation functions were measured in the 20.8-49.2 MeV energy range for the natPt(d,xn)191,192,193,194,195,196m2,196g,198g,199Au, natPt(d,x)188,189,191,195m,197m,197gPt and natPt(d,x)189,190,192,194m2Ir reactions by using the stacked foil irradiation technique. The experimental results are compared with previous results from the literature and with the theoretical predictions in the TENDL-2014 and TENDL-2015 libraries. The applicability of the produced radio-tracers for wear measurements has been presented.

  2. Annexin A1 down-regulation in head and neck squamous cell carcinoma is mediated via transcriptional control with direct involvement of miR-196a/b.

    PubMed

    Álvarez-Teijeiro, Saúl; Menéndez, Sofía T; Villaronga, M Ángeles; Pena-Alonso, Emma; Rodrigo, Juan P; Morgan, Reginald O; Granda-Díaz, Rocío; Salom, Cecilia; Fernandez, M Pilar; García-Pedrero, Juana M

    2017-07-28

    Annexin A1 (ANXA1) down-regulation is an early and frequent event in the development of head and neck squamous cell carcinomas (HNSCC). In an attempt to identify the underlying mechanisms of reduced ANXA1 protein expression, this study investigated ANXA1 mRNA expression in HNSCC specimens by both in situ hybridization and RT-qPCR. Results showed a perfect concordance between the pattern of ANXA1 mRNA and protein detected by immunofluorescence in tumors, precancerous lesions and normal epithelia, reflecting that ANXA1 down-regulation occurs at transcriptional level. We also found that both miR-196a and miR-196b levels inversely correlated with ANXA1 mRNA levels in paired HNSCC tissue samples and patient-matched normal mucosa. In addition, endogenous levels of ANXA1 mRNA and protein were consistently and significantly down-regulated upon miR-196a and miR-196b over-expression in various HNSCC-derived cell lines. The direct interaction of both mature miR-196a and miR-196b was further confirmed by transfection with Anxa1 3'UTR constructs. Combined bioinformatics and functional analysis of ANXA1 promoter activity contributed to identify key regions and potential mediators of ANXA1 transcriptional control. This study unveils that, in addition to miR-196a, miR-196b also directly targets ANXA1 in HNSCC.

  3. Catalytic Activity of Platinum Monolayer on Iridium and Rhenium Alloy Nanoparticles for the Oxygen Reduction Reaction

    SciTech Connect

    Karan, Hiroko I.; Sasaki, Kotaro; Kuttiyiel, Kurian; Farberow, Carrie A.; Mavrikakis, Manos; Adzic, Radoslav R.

    2012-05-04

    A new type of electrocatalyst with a core–shell structure that consists of a platinum monolayer shell placed on an iridium–rhenium nanoparticle core or platinum and palladium bilayer shell deposited on that core has been prepared and tested for electrocatalytic activity for the oxygen reduction reaction. Carbon-supported iridium–rhenium alloy nanoparticles with several different molar ratios of Ir to Re were prepared by reducing metal chlorides dispersed on Vulcan carbon with hydrogen gas at 400 °C for 1 h. These catalysts showed specific electrocatalytic activity for oxygen reduction reaction comparable to that of platinum. The activities of PtML/PdML/Ir2Re1, PtML/Pd2layers/Ir2Re1, and PtML/Pd2layers/Ir7Re3 catalysts were, in fact, better than that of conventional platinum electrocatalysts, and their mass activities exceeded the 2015 DOE target. Our density functional theory calculations revealed that the molar ratio of Ir to Re affects the binding strength of adsorbed OH and, thereby, the O2 reduction activity of the catalysts. The maximum specific activity was found for an intermediate OH binding energy with the corresponding catalyst on the top of the volcano plot. The monolayer concept facilitates the use of much less platinum than in other approaches. Finally, the results with the PtML/PdML/Ir2Re electrocatalyst indicate that it is a promising alternative to conventional Pt electrocatalysts in low-temperature fuel cells.

  4. Cross section of the 197Au(n,2n)196Au reaction

    NASA Astrophysics Data System (ADS)

    Kalamara, A.; Vlastou, R.; Kokkoris, M.; Diakaki, M.; Serris, M.; Patronis, N.; Axiotis, M.; Lagoyannis, A.

    2017-09-01

    The 197Au(n,2n)196Au reaction cross section has been measured at two energies, namely at 17.1 MeV and 20.9 MeV, by means of the activation technique, relative to the 27Al(n,α)24Na reference reaction cross section. Quasi-monoenergetic neutron beams were produced at the 5.5 MV Tandem T11/25 accelerator laboratory of NCSR "Demokritos", by means of the 3H(d,n)4He reaction, implementing a new Ti-tritiated target of ˜ 400 GBq activity. The induced γ-ray activity at the targets and reference foils has been measured with HPGe detectors. The cross section for the population of the second isomeric (12-) state m2 of 196Au was independently determined. Auxiliary Monte Carlo simulations were performed using the MCNP code. The present results are in agreement with previous experimental data and with theoretical calculations of the measured reaction cross sections, which were carried out with the use of the EMPIRE code.

  5. 46 CFR 196.34-20 - Shipboard inspections.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... service, but shall not be stamped by a marine inspector with a Coast Guard stamp. If a work vest is found not to be in a serviceable condition, then such work vest shall be removed from the vessel. If a work... Work Vests § 196.34-20 Shipboard inspections. (a) Each work vest shall be subject to examination by...

  6. 38 CFR 17.196 - Aid for hospital care.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Aid for hospital care. 17... to States for Care of Veterans in State Homes § 17.196 Aid for hospital care. Aid may be paid to the designated State official for hospital care furnished in a recognized State home for any veteran if: (a) The...

  7. 46 CFR 196.34-15 - Shipboard stowage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Work Vests § 196.34-15 Shipboard stowage. (a) The approved buoyant work vests shall be stowed separately from the regular stowage of approved life preservers. (b) The locations for the stowage of work vests...

  8. 14 CFR 19-6 - Public disclosure of traffic data.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... AIR CARRIERS Operating Statistics Classifications Section 19-6 Public disclosure of traffic data. (a... database is complete, but no earlier than six months after the date of the data. Military operations are... international summary statistics without carrier detail. Further, the Department may release nonstop segment and...

  9. 46 CFR 196.80-1 - Master's responsibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Explosive Handling Plan § 196.80-1 Master's responsibility. (a) It shall be the responsibility of the master..., plans, and safety precautions for all operations involving the use of explosives. (b) The operating...

  10. 46 CFR 196.36-1 - When required.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS OPERATIONS Display of Plans § 196.36-1 When required. (a) All manned vessels shall have permanently exhibited for the guidance of the officer in charge of the vessel, general arrangement plans showing for each deck the various...

  11. 32 CFR 196.100 - Purpose and effective date.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... FINANCIAL ASSISTANCE Introduction § 196.100 Purpose and effective date. The purpose of these Title IX regulations is to effectuate Title IX of the Education Amendments of 1972, as amended (except sections 904 and... an educational institution as defined in these Title IX regulations. The effective date of...

  12. 32 CFR 196.100 - Purpose and effective date.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... FINANCIAL ASSISTANCE Introduction § 196.100 Purpose and effective date. The purpose of these Title IX regulations is to effectuate Title IX of the Education Amendments of 1972, as amended (except sections 904 and... an educational institution as defined in these Title IX regulations. The effective date of...

  13. 32 CFR 196.100 - Purpose and effective date.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... FINANCIAL ASSISTANCE Introduction § 196.100 Purpose and effective date. The purpose of these Title IX regulations is to effectuate Title IX of the Education Amendments of 1972, as amended (except sections 904 and... an educational institution as defined in these Title IX regulations. The effective date of...

  14. 32 CFR 196.100 - Purpose and effective date.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... FINANCIAL ASSISTANCE Introduction § 196.100 Purpose and effective date. The purpose of these Title IX regulations is to effectuate Title IX of the Education Amendments of 1972, as amended (except sections 904 and... an educational institution as defined in these Title IX regulations. The effective date of...

  15. 32 CFR 196.100 - Purpose and effective date.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... FINANCIAL ASSISTANCE Introduction § 196.100 Purpose and effective date. The purpose of these Title IX regulations is to effectuate Title IX of the Education Amendments of 1972, as amended (except sections 904 and... an educational institution as defined in these Title IX regulations. The effective date of...

  16. 37 CFR 1.96 - Submission of computer program listings.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2014-07-01 2014-07-01 false Submission of computer... Models, Exhibits, Specimens § 1.96 Submission of computer program listings. (a) General. Descriptions of the operation and general content of computer program listings should appear in the description...

  17. 37 CFR 1.96 - Submission of computer program listings.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Submission of computer... Models, Exhibits, Specimens § 1.96 Submission of computer program listings. (a) General. Descriptions of the operation and general content of computer program listings should appear in the description...

  18. 37 CFR 1.96 - Submission of computer program listings.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2012-07-01 2012-07-01 false Submission of computer... Models, Exhibits, Specimens § 1.96 Submission of computer program listings. (a) General. Descriptions of the operation and general content of computer program listings should appear in the description...

  19. 37 CFR 1.96 - Submission of computer program listings.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Submission of computer... Models, Exhibits, Specimens § 1.96 Submission of computer program listings. (a) General. Descriptions of the operation and general content of computer program listings should appear in the description...

  20. 37 CFR 1.96 - Submission of computer program listings.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Submission of computer... Models, Exhibits, Specimens § 1.96 Submission of computer program listings. (a) General. Descriptions of the operation and general content of computer program listings should appear in the description...