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Sample records for platinum 194 target

  1. MiR-194 Deregulation Contributes To Colorectal Carcinogenesis via Targeting AKT2 Pathway

    PubMed Central

    Zhao, Hui-Jun; Ren, Lin-Lin; Wang, Zhen-Hua; Sun, Tian-Tian; Yu, Ya-Nan; Wang, Ying-Chao; Yan, Ting-Ting; Zou, Weiping; He, Jie; Zhang, Yaou; Hong, Jie; Fang, Jing-Yuan

    2014-01-01

    Abstract: Recent studies have increasingly linked microRNAs to colorectal cancer (CRC). MiR-194 has been reported deregulated in different tumor types, whereas the function of miR-194 in CRC largely remains unexplored. Here we investigated the biological effects, mechanisms and clinical significance of miR-194. Functional assay revealed that overexpression of miR-194 inhibited CRC cell viability and invasion in vitro and suppressed CRC xenograft tumor growth in vivo. Conversely, block of miR-194 in APCMin/+ mice promoted tumor growth. Furthermore, miR-194 reduced the expression of AKT2 both in vitro and in vivo. Clinically, the expression of miR-194 gradually decreased from 20 normal colorectal mucosa (N-N) cases through 40 colorectal adenomas (CRA) cases and then to 40 CRC cases, and was negatively correlated with AKT2 and pAKT2 expression. Furthermore, expression of miR-194 in stool samples was gradually decreased from 20 healthy cases, 20 CRA cases, then to 28 CRC cases. Low expression of miR-194 in CRC tissues was associated with large tumor size (P=0.006), lymph node metastasis (P=0.012) and shorter survival (HR =2.349, 95% CI = 1.242 to 4.442; P=0.009). In conclusion, our data indicated that miR-194 acted as a tumor suppressor in the colorectal carcinogenesis via targeting PDK1/AKT2/XIAP pathway, and could be a significant diagnostic and prognostic biomarker for CRC. PMID:25285168

  2. 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

  3. 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.

  4. MicroRNA-194 regulates keratinocyte proliferation and differentiation by targeting Grainyhead-like 2 in psoriasis.

    PubMed

    Yu, Xiaoyun; An, Jingang; Hua, Yunhui; Li, Zihai; Yan, Ning; Fan, Weixin; Su, Chuan

    2017-02-01

    MicroRNAs (miRNAs) are currently emerged as important regulators in psoriasis. Psoriasis is characterized by hyperproliferation and impaired differentiation of keratinocytes in skin lesions. miR-194 is a well-known regulator of cell proliferation and differentiation. However, the role of miR-194 in psoriasis pathogenesis remains unclear. In this study we aimed to investigate the role of miR-194 in keratinocyte hyperproliferation and differentiation. We found that miR-194 was significantly downregulated in psoriasis lesional skin. Overexpression of miR-194 inhibited the proliferation and promoted the differentiation of primary human keratinocytes, whereas miR-194 suppression promoted the proliferation and inhibited their differentiation. Bioinformatic analysis predicted that the Grainyhead-like 2 (GRHL2) was a target gene of miR-194, which we further validated with a dual-luciferase reporter assay, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot analysis. The effect of miR-194 on cell proliferation and differentiation was significantly reversed by overexpression of GRHL2. Moreover, the expression of miR-194 and GRHL2 was inversely correlated in psoriasis lesional skin. Taken together, our results suggest that miR-194 inhibits the proliferation and promotes the differentiation of keratinocytes through targeting GRHL2. The downregulation of miR-194 expression may contribute to the pathogenesis of psoriasis and targeting miR-194 may represent a novel and potential therapeutic strategy for psoriasis.

  5. 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.

  6. 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.

  7. microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R.

    PubMed

    Han, Kang; Zhao, Tingbao; Chen, Xiang; Bian, Na; Yang, Tongtao; Ma, Qiong; Cai, Chengkui; Fan, Qingyu; Zhou, Yong; Ma, Baoan

    2014-10-01

    Studies have shown that miR-194 functions as a tumor suppressor and is associated with tumor growth and metastasis. We studied the effects of miR-194 in osteosarcoma and the possible mechanism by which miR-194 affected the survival, apoptosis and metastasis of osteosarcoma. Both human osteosarcoma cell lines SOSP-9607 and U2-OS were transfected with recombinant lentiviruses to regulate miR-194 expression. Overexpression of miR-194 partially inhibited the proliferation, migration, and invasion of osteosarcoma cells in vitro, as well as tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. Potential miR-194 target genes were predicted using bioinformatics. Luciferase reporter assay, real-time quantitative PCR and western blotting confirmed that CDH2 (N-cadherin) and IGF1R were targets of miR-194. Using real-time quantitative PCR, we evaluated the expression of miR-194 and two miR-194 target genes, CDH2 and IGF1R in osteosarcoma samples from 107 patients and 99 formalin- or paraformalin-fixed paraffin-embedded tissues. The expressions of the target genes were also examined in osteosarcoma samples using immunohistochemistry. Overexpression of miR-194 inhibited tumor growth and metastasis of osteosarcoma probably by downregulating CDH2 and IGF1R. miR-194 may prove to be a promising therapeutic agent for osteosarcoma.

  8. microRNA-194 suppresses osteosarcoma cell proliferation and metastasis in vitro and in vivo by targeting CDH2 and IGF1R

    PubMed Central

    HAN, KANG; ZHAO, TINGBAO; CHEN, XIANG; BIAN, NA; YANG, TONGTAO; MA, QIONG; CAI, CHENGKUI; FAN, QINGYU; ZHOU, YONG; MA, BAOAN

    2014-01-01

    Studies have shown that miR-194 functions as a tumor suppressor and is associated with tumor growth and metastasis. We studied the effects of miR-194 in osteosarcoma and the possible mechanism by which miR-194 affected the survival, apoptosis and metastasis of osteosarcoma. Both human osteosarcoma cell lines SOSP-9607 and U2-OS were transfected with recombinant lentiviruses to regulate miR-194 expression. Overexpression of miR-194 partially inhibited the proliferation, migration, and invasion of osteosarcoma cells in vitro, as well as tumor growth and pulmonary metastasis of osteosarcoma cells in vivo. Potential miR-194 target genes were predicted using bioinformatics. Luciferase reporter assay, real-time quantitative PCR and western blotting confirmed that CDH2 (N-cadherin) and IGF1R were targets of miR-194. Using real-time quantitative PCR, we evaluated the expression of miR-194 and two miR-194 target genes, CDH2 and IGF1R in osteosarcoma samples from 107 patients and 99 formalin- or paraformalin-fixed paraffin-embedded tissues. The expressions of the target genes were also examined in osteosarcoma samples using immunohistochemistry. Overexpression of miR-194 inhibited tumor growth and metastasis of osteosarcoma probably by downregulating CDH2 and IGF1R. miR-194 may prove to be a promising therapeutic agent for osteosarcoma. PMID:25096247

  9. 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.

  10. Original Research: miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells.

    PubMed

    Cui, Guanghui; Liu, Donglei; Li, Weihao; Li, Yuhang; Liang, Youguang; Shi, Wensong; Zhao, Song

    2017-01-01

    Increasing evidence suggests that miR-194 is down-regulated in esophageal squamous cell carcinoma tumor tissue. However, the role and underlying mechanism of miR-194 in esophageal squamous cell carcinoma have not been well defined. We used DIANA, TargetScan and miRanda to perform target prediction analysis and found KDM5B is a potential target of miR-194. Based on these findings, we speculated that miR-194 might play a role in esophageal squamous cell carcinoma development and progression by regulation the expression of KDM5B. We detected the expression of miR-194 and KDM5B by quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot assays, respectively, and found down-regulation of miR-194 and up-regulation of KDM5B existed in esophageal squamous cell carcinoma cell lines. By detecting proliferation, invasion and apoptosis of TE6 and TE14 cells transfected with miR-194 mimics or mimic control, miR-194 was found to inhibit proliferation and invasion and promote apoptosis of esophageal squamous cell carcinoma cells. miR-194 was further verified to regulate proliferation, apoptosis and invasion of esophageal squamous cell carcinoma cells by directly targeting KDM5B. Furthermore, animal studies were performed and showed that overexpression of miR-194 inhibited the growth of esophageal squamous cell carcinoma tumors in vivo. These results confirmed our speculation that miR-194 targets KDM5B to inhibit esophageal squamous cell carcinoma development and progression. These findings offer new clues for esophageal squamous cell carcinoma development and progression and novel potential therapeutic targets for esophageal squamous cell carcinoma. © 2016 by the Society for Experimental Biology and Medicine.

  11. 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.

  12. 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

  13. 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.

  14. MicroRNA-194 inhibition improves dietary-induced non-alcoholic fatty liver disease in mice through targeting on FXR.

    PubMed

    Nie, Hezhongrong; Song, Chunli; Wang, Daming; Cui, Shengjin; Ren, Tingyu; Cao, Zhaopeng; Liu, Qing; Chen, Zeyan; Chen, Xiaoyong; Zhou, Yiwen

    2017-09-22

    Non-alcoholic fatty liver disease (NAFLD) affects obesity-associated metabolic syndrome, which exhibits hepatic steatosis, insulin insensitivity and glucose intolerance. Previous studies indicated that hepatic microRNAs (miRs) play critical roles in the development of NAFLD. In this study, we aim to explore the pathophysiological role of miR-194 in obesity-mediated metabolic dysfunction. Our findings show that the high fat diet or palmitic acid treatment significantly increase hepatic miR-194 levels in vivo and in vitro. Silence of miR-194 protects palmitic acid-induced inflammatory response in cultured hepatocytes, and attenuates structural disorders, lipid deposits and inflammatory response in fatty liver. MiR-194 inhibitor also improves glucose and insulin intolerance in obese mice. Through dual luciferase assay, we demonstrate that miR-194 directly binds to FXR/Nr1h4 3'-UTR, and inhibits gene expression of FXR/Nr1h4. Furthermore, overexpression of miR-194 downregulates FXR/Nr1h4 in cultured hepatocytes, but miR-194 inhibitor reversely increases FXR/Nr1h4 expression in obese mouse liver tissues. On the contrast, silence of FXR/Nr1h4 abolishes the hepatic benefits in obese mice treated with miR-194 inhibitor. Present study provides a novel finding that suppression of miR-194 attenuates dietary-induced NAFLD via upregulation of FXR/Nr1h4. The findings suggest miR-194/FXR are potential diagnostic markers and therapeutic targets for NAFLD. Copyright © 2017. Published by Elsevier B.V.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Overexpression of microRNA-194 suppresses the epithelial-mesenchymal transition in targeting stem cell transcription factor Sox3 in endometrial carcinoma stem cells.

    PubMed

    Gong, Baolan; Yue, Yan; Wang, Renxiao; Zhang, Yi; Jin, Quanfang; Zhou, Xi

    2017-06-01

    The epithelial-mesenchymal transition is the key process driving cancer metastasis. MicroRNA-194 inhibits epithelial-mesenchymal transition in several cancers and its downregulation indicates a poor prognosis in human endometrial carcinoma. Self-renewal factor Sox3 induces epithelial-mesenchymal transition at gastrulation and is also involved epithelial-mesenchymal transition in several cancers. We intended to determine the roles of Sox3 in inducing epithelial-mesenchymal transition in endometrial cancer stem cells and the possible role of microRNA-194 in controlling Sox3 expression. Firstly, we found that Sox3 and microRNA-194 expressions were associated with the status of endometrial cancer stem cells in a panel of endometrial carcinoma tissue, the CD133+ cell was higher in tumorsphere than in differentiated cells, and overexpression of microRNA-194 would decrease CD133+ cell expression. Silencing of Sox3 in endometrial cancer stem cell upregulated the epithelial marker E-cadherin, downregulated the mesenchymal marker vimentin, and significantly reduced cell invasion in vitro; overexpression of Sox3 reversed these phenotypes. Furthermore, we discovered that the expression of Sox3 was suppressed by microRNA-194 through direct binding to the Sox3 3'-untranslated region. Ectopic expression of microRNA-194 in endometrial cancer stem cells induced a mesenchymal-epithelial transition by restoring E-cadherin expression, decreasing vimentin expression, and inhibiting cell invasion in vitro. Moreover, overexpression of microRNA-194 inhibited endometrial cancer stem cell invasion or metastasis in vivo by injection of adenovirus microRNA-194. These findings demonstrate the novel mechanism by which Sox3 contributes to endometrial cancer stem cell invasion and suggest that repression of Sox3 by microRNA-194 may have therapeutic potential to suppress endometrial carcinoma metastasis. The cancer stem cell marker, CD133, might be the surface marker of endometrial cancer stem

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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.

  2. Cellular processing of the interleukin-2 fusion toxin DAB486-IL-2 and efficient delivery of diphtheria fragment A to the cytosol of target cells requires Arg194.

    PubMed

    Williams, D P; Wen, Z; Watson, R S; Boyd, J; Strom, T B; Murphy, J R

    1990-11-25

    We have used site-directed mutagenesis to examine the role played by Arg191, Arg193, and Arg194 of the fusion toxin DAB486-IL-2 in the intoxication of high affinity interleukin-2 receptor-bearing T-lymphocytes. These arginine residues are positioned in the proteolytically sensitive 14-amino acid loop subtended by the disulfide bond between Cys187 and Cys202 in this fusion toxin. DAB486-IL-2 was formed by the genetic substitution of the native diphtheria toxin receptor binding domain with human interleukin-2 (Williams, D.P., Parker, K., Bacha, P., Bishai, W., Borowski, M., Genbauffe, F., Strom, T.B., and Murphy, J.R. (1987) Protein Eng. 1, 493-498). We demonstrate that substitution of Arg194 with Gly results in a 1000-fold loss of DAB486-IL-2 potency. Since trypsin "nicking" of the Gly194 mutant restores biologic activity, we conclude that Arg194 is required for the cellular processing of the fusion toxin which results in the release of fragment A into the cytosol.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 49 CFR 194.113 - Information summary.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Information summary. 194.113 Section 194.113... Response Plans § 194.113 Information summary. (a) The information summary for the core plan, required by... state(s). (b) The information summary for the response zone appendix, required in § 194.107, must...

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 46 CFR 194.20-9 - Storage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemical Stores and/or Storerooms § 194.20-9 Storage. (a) Chemical stores shall be stored in the chemical storeroom as prescribed in § 194.05-1(b). (b) All items stored...

  6. 46 CFR 194.15-9 - Storage.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-9 Storage. (a) Chemical stores mentioned in § 194.05-3 may be stored in small working quantities in the laboratory provided their containers are labeled in accordance with § 194.05-5(a). (b) Chemical stores in...

  7. 46 CFR 194.15-9 - Storage.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-9 Storage. (a) Chemical stores mentioned in § 194.05-3 may be stored in small working quantities in the laboratory provided their containers are labeled in accordance with § 194.05-5(a). (b) Chemical stores in...

  8. 46 CFR 194.15-9 - Storage.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-9 Storage. (a) Chemical stores mentioned in § 194.05-3 may be stored in small working quantities in the laboratory provided their containers are labeled in accordance with § 194.05-5(a). (b) Chemical stores in...

  9. 40 CFR 194.3 - Communications.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Communications. 194.3 Section 194.3... CFR PART 191 DISPOSAL REGULATIONS General Provisions § 194.3 Communications. (a) Compliance...) Communications and reports concerning the criteria in this part shall be: (1) Addressed to the Administrator or...

  10. 40 CFR 194.3 - Communications.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Communications. 194.3 Section 194.3... CFR PART 191 DISPOSAL REGULATIONS General Provisions § 194.3 Communications. (a) Compliance...) Communications and reports concerning the criteria in this part shall be: (1) Addressed to the Administrator or...

  11. 40 CFR 194.22 - Quality assurance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Quality assurance. 194.22 Section 194... General Requirements § 194.22 Quality assurance. (a)(1) As soon as practicable after April 9, 1996, the Department shall adhere to a quality assurance program that implements the requirements of ASME...

  12. 40 CFR 194.22 - Quality assurance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Quality assurance. 194.22 Section 194... General Requirements § 194.22 Quality assurance. (a)(1) As soon as practicable after April 9, 1996, the Department shall adhere to a quality assurance program that implements the requirements of ASME...

  13. 40 CFR 194.22 - Quality assurance.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Quality assurance. 194.22 Section 194... General Requirements § 194.22 Quality assurance. (a)(1) As soon as practicable after April 9, 1996, the Department shall adhere to a quality assurance program that implements the requirements of ASME...

  14. 40 CFR 194.22 - Quality assurance.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Quality assurance. 194.22 Section 194... General Requirements § 194.22 Quality assurance. (a)(1) As soon as practicable after April 9, 1996, the Department shall adhere to a quality assurance program that implements the requirements of ASME...

  15. 40 CFR 194.22 - Quality assurance.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Quality assurance. 194.22 Section 194... General Requirements § 194.22 Quality assurance. (a)(1) As soon as practicable after April 9, 1996, the Department shall adhere to a quality assurance program that implements the requirements of ASME...

  16. 49 CFR 194.117 - Training.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Training. 194.117 Section 194.117 Transportation... Response Plans § 194.117 Training. (a) Each operator shall conduct training to ensure that: (1) All... of equipment, fire suits, and breathing apparatus. (b) Each operator shall maintain a training record...

  17. 49 CFR 194.117 - Training.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Training. 194.117 Section 194.117 Transportation... Response Plans § 194.117 Training. (a) Each operator shall conduct training to ensure that: (1) All... of equipment, fire suits, and breathing apparatus. (b) Each operator shall maintain a training record...

  18. 49 CFR 194.117 - Training.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Training. 194.117 Section 194.117 Transportation... Response Plans § 194.117 Training. (a) Each operator shall conduct training to ensure that: (1) All... of equipment, fire suits, and breathing apparatus. (b) Each operator shall maintain a training record...

  19. 49 CFR 194.117 - Training.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Training. 194.117 Section 194.117 Transportation... Response Plans § 194.117 Training. (a) Each operator shall conduct training to ensure that: (1) All... of equipment, fire suits, and breathing apparatus. (b) Each operator shall maintain a training record...

  20. 49 CFR 194.115 - Response resources.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Response resources. 194.115 Section 194.115... Response Plans § 194.115 Response resources. (a) Each operator shall identify and ensure, by contract or other approved means, the resources necessary to remove, to the maximum extent practicable, a worst...

  1. 49 CFR 194.115 - Response resources.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Response resources. 194.115 Section 194.115... Response Plans § 194.115 Response resources. (a) Each operator shall identify and ensure, by contract or other approved means, the resources necessary to remove, to the maximum extent practicable, a worst...

  2. 49 CFR 194.115 - Response resources.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Response resources. 194.115 Section 194.115... Response Plans § 194.115 Response resources. (a) Each operator shall identify and ensure, by contract or other approved means, the resources necessary to remove, to the maximum extent practicable, a worst...

  3. 49 CFR 194.115 - Response resources.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Response resources. 194.115 Section 194.115... Response Plans § 194.115 Response resources. (a) Each operator shall identify and ensure, by contract or other approved means, the resources necessary to remove, to the maximum extent practicable, a worst...

  4. 49 CFR 194.115 - Response resources.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Response resources. 194.115 Section 194.115... Response Plans § 194.115 Response resources. (a) Each operator shall identify and ensure, by contract or other approved means, the resources necessary to remove, to the maximum extent practicable, a worst...

  5. 46 CFR 194.15-5 - Ventilation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Ventilation. 194.15-5 Section 194.15-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194...

  6. 46 CFR 194.15-5 - Ventilation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Ventilation. 194.15-5 Section 194.15-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194...

  7. 46 CFR 194.15-19 - Electrical.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Electrical. 194.15-19 Section 194.15-19 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194...

  8. 46 CFR 194.15-9 - Storage.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Storage. 194.15-9 Section 194.15-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-9 Storage...

  9. 46 CFR 194.15-1 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false General. 194.15-1 Section 194.15-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-1 General...

  10. 46 CFR 194.15-1 - General.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false General. 194.15-1 Section 194.15-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-1 General...

  11. 46 CFR 194.15-9 - Storage.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Storage. 194.15-9 Section 194.15-9 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-9 Storage...

  12. 46 CFR 194.15-19 - Electrical.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Electrical. 194.15-19 Section 194.15-19 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194...

  13. 50 CFR 19.4 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 6 2010-10-01 2010-10-01 false Definitions. 19.4 Section 19.4 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) TAKING... (CONTINUED) AIRBORNE HUNTING Introduction § 19.4 Definitions. In addition to definitions contained in part...

  14. 42 CFR 460.194 - Corrective action.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Corrective action. 460.194 Section 460.194 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Federal/State Monitoring § 460.194 Corrective action. (a) A PACE organization must take action to...

  15. 40 CFR 194.3 - Communications.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Communications. 194.3 Section 194.3... CFR PART 191 DISPOSAL REGULATIONS General Provisions § 194.3 Communications. (a) Compliance...) Communications and reports concerning the criteria in this part shall be: (1) Addressed to the Administrator...

  16. 49 CFR 194.117 - Training.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Training. 194.117 Section 194.117 Transportation... Response Plans § 194.117 Training. (a) Each operator shall conduct training to ensure that: (1) All... of equipment, fire suits, and breathing apparatus. (b) Each operator shall maintain a training...

  17. 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

  18. 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.

  19. MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1

    SciTech Connect

    Li, Jun; He, Xijing; Wei, Wenzhi; Zhou, Xiaobo

    2015-05-01

    Osteoblast differentiation is a vital process in maintaining bone homeostasis in which various transcriptional factors, signaling molecules, and microRNAs (miRNAs) are involved. Recently, signal transducer and activator of transcription 1 (STAT1) has been found to play an important role in regulating osteoblast differentiation. Here, we identified that STAT1 expression was regulated by miR-194. Using mouse bone mesenchymal stem cells (BMSCs), we found that miR-194 expression was significantly increased following osteoblast differentiation induction. Overexpression of miR-194 by lentivirus-mediated gene transfer markedly increased osteoblast differentiation, whereas inhibition of miR-194 significantly suppressed osteoblast differentiation of BMSCs. Using a dual-luciferase reporter assay, a direct interaction between miR-194 and the 3′-untranslated region (UTR) of STAT1 was confirmed. Additionally, miR-194 regulated mRNA and protein expression of STAT1 in BMSCs. Further analysis showed that miR-194 overexpression promoted the nuclear translocation of runt-related transcription factor 2 (Runx2), which is critical for osteoblast differentiation. In contrast, inhibition of miR-194 blocked the nuclear translocation of Runx2. Moreover, overexpression of STAT1 significantly blocked Runx2 nuclear translocation and osteoblast differentiation mediated by miR-194 overexpression. Taken together, our data suggest that miR-194 regulates osteoblast differentiation through modulating STAT1-mediated Runx2 nuclear translocation. - Highlights: • Overexpression of miR-194 significantly increased osteoblast differentiation. • miR-194 directly targeted the 3′- UTR of STAT1. • miR-194 regulated the expression of STAT1. • Overexpression of miR-194 promoted the nuclear translocation of Runx2.

  20. 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.

  1. 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...

  2. 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...

  3. Structural and functional evaluation of interaction between mammalian ribosomal RNA with platinum-containing antineoplastic drugs.

    PubMed

    Theile, Dirk; Kos, Martin

    2016-02-03

    Cisplatin, oxaliplatin, and carboplatin primarily target DNA, but also alter RNA functionality, albeit to different extent. This study determined the in vitro cytotoxicity (IC50 values) of platinum drugs in LS180 cells and compared the rRNA platination patterns following IC50 exposure. Relevance of particular secondary RNA structures for platination susceptibility was evaluated by primer extension methodology using 18S rRNA as a model RNA. Consequences of rRNA platination for translation efficiency were evaluated by monitoring fluorescence of a destabilised green fluorescent protein variant through flow cytometry. Oxaliplatin and cisplatin were most cytotoxic with IC50 values of 1.7 μM±0.8 and 4.1 μM±0.1, respectively. Carboplatin was significantly less efficient (IC50 147.1 μM±19.4). When exposed to equitoxic concentrations (respective IC50), all three compounds caused similar stop signal incidence or intensity. Moreover, the same rRNA sites were targeted without selectivity for particular secondary structures but with a slight preference for guanine-rich regions. Compared to cycloheximide, none of the drugs diminished translation efficiency at typical in vivo concentrations. In conclusion, equitoxic concentrations of platinum drugs target the same sites in cellular rRNA and cause similar platination intensities. At pharmacokinetically relevant concentrations, cisplatin, oxaliplatin or carboplatin do not inhibit translation efficiency. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. 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.

  5. Nuclear Data Sheets for A = 194

    SciTech Connect

    Singh, Balraj

    2006-06-15

    Nuclear spectroscopic information for known nuclides of mass number 194 (Re,Os,Ir,Pt,Au,Hg,Tl,Pb,Bi, Po,At) with Z = 75 to 85 and N = 119 to 109 have been evaluated and presented together with adopted energies and J{pi} of levels in these nuclei. No excited state data are yet available for {sup 194}Re and {sup 194}At. Many superdeformed structures are known in A = 194: three SD bands in {sup 194}Hg, two of which are connected to the normal-deformed structures; six SD bands in {sup 194}Tl; and three SD bands in {sup 194}Pb, one of which is connected to the normal-deformed structure. In addition four magnetic-rotational (MR) dipole bands are known in {sup 194}Pb together with many other dipole bands which are probable multi-quasiparticle structures. This evaluation supersedes previous full evaluations of A = 194 published by 1996Br26, 1989Si01, 1977Ha46 and 1972Au11.

  6. Studies of {sup 194,195,197}Po

    SciTech Connect

    Carpenter, M.P.; Ahmad, I.; Crowell, B.

    1995-08-01

    The energy systematics of low-lying polonium states show sudden changes near N = 114. The observed drops in the low-lying levels of {sup 196,198}Po relative to the heavier isotopes indicate significant changes in the underlying structure of these nuclei. It is thought that this change is due to the onset of vibrational collectivity brought about by the quadrupole interaction between neutron and proton-pairs. In order to extend the Po systematics even further, we measured, for the first time, states in {sup 194,195,197}Po using the {sup 28}Si + {sup 170}Yb reaction at a beam energy of 142 MeV. The beam was supplied by ATLAS, and the data were taken with 10 Compton-suppressed Ge detectors placed at the target position of the Fragment Mass Analyzer. Preliminary level schemes were constructed for {sup 194,195,197}Po based on {gamma}-{gamma} and {gamma}-FMA coincidences. The results for {sup 194}Po show that the 2{sup +} - 0{sup +} transition energy decreased in energy by 140 keV relative to {sup 196}Po suggesting that this nucleus moved beyond the vibrational limit to more collective motion. An extrapolation of the systematics predicts that the 2{sup +} energy could drop another 140 keV between {sup 194}Po and {sup 192}Po which would indicate the onset of rotational motion. Currently, we have an approved experiment to investigate the decay of yrast isomers in {sup 194}Po which will allow us to (1) confirm our earlier level scheme of {sup 194}Po, and (2) assess the experimental conditions needed for a future study of {sup 192}Po.

  7. miR-194 functions as a novel modulator of cellular senescence in mouse embryonic fibroblasts.

    PubMed

    Xu, Shun; Zhang, Bing; Zhu, Yanmei; Huang, Haijiao; Yang, Wenping; Huang, Haiyong; Zheng, Hui-Ling; Liu, Xinguang

    2017-03-01

    MicroRNA-194 (miR-194), a typical p53 responsive miRNA, serves as a tumor suppressor similar as p53, and has been demonstrated to play an anti-proliferation role in various human cancers. In spite of the pivotal role of p53 during aging process, the knowledge of miR-194's contribution to cellular senescence is limited. We herein sought to explore the role of miR-194 in the replicative senescence and stress-induced senescence of mouse embryonic fibroblasts. Our results unraveled that, compared to young cells, miR-194 is highly expressed in senescent cells, and extra expression of miR-194 significantly triggers the replicative senescence of MEFs and H2 O2 -induced senescence of NIH/3T3 cells, while inhibition of miR-194 exhibited the opposite effect. We further unveiled that DNMT3A was a direct and authentic target of miR-194, which has been reported to be closely associated with cellular senescence. Taken together, our data suggest that miR-194 may significantly promote the development of cellular senescence in mouse embryonic fibroblasts, which potentially occurs through inhibiting the DNMT3A expression.

  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. 40 CFR 194.6 - Alternative provisions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Alternative provisions. 194.6 Section... COMPLIANCE WITH THE 40 CFR PART 191 DISPOSAL REGULATIONS General Provisions § 194.6 Alternative provisions. The Administrator may, by rule pursuant to 5 U.S.C. 553, substitute for any of the provisions of...

  10. 46 CFR 194.15-19 - Electrical.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Electrical. 194.15-19 Section 194.15-19 Shipping COAST....15-19 Electrical. (a) All electrical equipment located within 18 inches of the deck of the chemical laboratory shall be in accordance with the applicable requirements of Subchapter J (Electrical Engineering...

  11. 46 CFR 194.15-19 - Electrical.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Electrical. 194.15-19 Section 194.15-19 Shipping COAST....15-19 Electrical. (a) All electrical equipment located within 18 inches of the deck of the chemical laboratory shall be in accordance with the applicable requirements of Subchapter J (Electrical...

  12. 46 CFR 194.20-3 - Responsibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Responsibility. 194.20-3 Section 194.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND... Responsibility. (a) With the knowledge and approval of the master the senior member of the scientific...

  13. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Responsibility. 194.15-3 Section 194.15-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND....15-3 Responsibility. (a) With the knowledge and approval of the master, the senior member of...

  14. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Responsibility. 194.15-3 Section 194.15-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND....15-3 Responsibility. (a) With the knowledge and approval of the master, the senior member of...

  15. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Responsibility. 194.15-3 Section 194.15-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND....15-3 Responsibility. (a) With the knowledge and approval of the master, the senior member of...

  16. 46 CFR 194.20-3 - Responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Responsibility. 194.20-3 Section 194.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND... Responsibility. (a) With the knowledge and approval of the master the senior member of the scientific...

  17. 46 CFR 194.20-3 - Responsibility.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Responsibility. 194.20-3 Section 194.20-3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND... Responsibility. (a) With the knowledge and approval of the master the senior member of the scientific...

  18. 49 CFR 19.4 - Deviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 1 2013-10-01 2013-10-01 false Deviations. 19.4 Section 19.4 Transportation Office of the Secretary of Transportation UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General §...

  19. 49 CFR 19.4 - Deviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 1 2012-10-01 2012-10-01 false Deviations. 19.4 Section 19.4 Transportation Office of the Secretary of Transportation UNIFORM ADMINISTRATIVE REQUIREMENTS FOR GRANTS AND AGREEMENTS WITH INSTITUTIONS OF HIGHER EDUCATION, HOSPITALS, AND OTHER NON-PROFIT ORGANIZATIONS General §...

  20. 46 CFR 194.15-5 - Ventilation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Ventilation of air conditioning systems serving the chemical laboratory shall be designed so that air cannot... 46 Shipping 7 2012-10-01 2012-10-01 false Ventilation. 194.15-5 Section 194.15-5 Shipping COAST....15-5 Ventilation. (a) Operations, reactions or experiments which produce toxic, noxious or...

  1. 46 CFR 194.15-5 - Ventilation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Ventilation of air conditioning systems serving the chemical laboratory shall be designed so that air cannot... 46 Shipping 7 2011-10-01 2011-10-01 false Ventilation. 194.15-5 Section 194.15-5 Shipping COAST....15-5 Ventilation. (a) Operations, reactions or experiments which produce toxic, noxious or...

  2. 40 CFR 194.44 - Engineered barriers.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Engineered barriers. 194.44 Section 194.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION... accessible environment. (b) In selecting any engineered barrier(s) for the disposal system, the...

  3. 40 CFR 194.42 - Monitoring.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Monitoring. 194.42 Section 194.42 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA... other effects of human intrusion in the vicinity of the disposal system; (5) Brine quantity,...

  4. 40 CFR 194.7 - Effective date.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Effective date. 194.7 Section 194.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40...

  5. 40 CFR 194.7 - Effective date.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Effective date. 194.7 Section 194.7 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40...

  6. 40 CFR 194.6 - Alternative provisions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Alternative provisions. 194.6 Section 194.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  7. 40 CFR 194.67 - Dockets.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Dockets. 194.67 Section 194.67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40...

  8. 40 CFR 194.21 - Inspections.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Inspections. 194.21 Section 194.21 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40...

  9. 40 CFR 194.21 - Inspections.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Inspections. 194.21 Section 194.21 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40...

  10. 40 CFR 194.3 - Communications.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Communications. 194.3 Section 194.3 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40...

  11. 40 CFR 194.67 - Dockets.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Dockets. 194.67 Section 194.67 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40...

  12. 42 CFR 460.194 - Corrective action.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Corrective action. 460.194 Section 460.194 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY...

  13. 42 CFR 460.194 - Corrective action.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Corrective action. 460.194 Section 460.194 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY (PACE) PROGRAMS OF ALL-INCLUSIVE CARE FOR THE ELDERLY...

  14. 46 CFR 194.20-5 - Ventilation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Ventilation. 194.20-5 Section 194.20-5 Shipping COAST... Ventilation. (a) Chemical storerooms shall be equipped with a power ventilation system of exhaust type. The... based upon the volume of the compartment. (1) Power ventilation units shall have nonsparking...

  15. 46 CFR 194.20-5 - Ventilation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Ventilation. 194.20-5 Section 194.20-5 Shipping COAST... Ventilation. (a) Chemical storerooms shall be equipped with a power ventilation system of exhaust type. The... based upon the volume of the compartment. (1) Power ventilation units shall have nonsparking...

  16. 40 CFR 194.24 - Waste characterization.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Waste characterization. 194.24 Section... PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... General Requirements § 194.24 Waste characterization. (a) Any compliance application shall describe the...

  17. 49 CFR 194.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... environmental impact of oil discharged from onshore oil pipelines. ... 49 Transportation 3 2010-10-01 2010-10-01 false Purpose. 194.1 Section 194.1 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY ADMINISTRATION...

  18. 46 CFR 194.90-1 - Requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Requirements. 194.90-1 Section 194.90-1 Shipping COAST...-1 Requirements. (a) Vessels contracted for prior to March 1, 1968, shall meet the following requirements: (1) Existing arrangements, materials, and facilities previously approved but not meeting the...

  19. 46 CFR 194.90-1 - Requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Requirements. 194.90-1 Section 194.90-1 Shipping COAST...-1 Requirements. (a) Vessels contracted for prior to March 1, 1968, shall meet the following requirements: (1) Existing arrangements, materials, and facilities previously approved but not meeting the...

  20. 46 CFR 194.90-1 - Requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Requirements. 194.90-1 Section 194.90-1 Shipping COAST...-1 Requirements. (a) Vessels contracted for prior to March 1, 1968, shall meet the following requirements: (1) Existing arrangements, materials, and facilities previously approved but not meeting the...

  1. 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.

  2. 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

  3. 46 CFR 194.15-19 - Electrical.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-19 Electrical. (a) All electrical equipment located within 18 inches of the deck of the chemical...

  4. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194... scientific party embarked may supervise the safety and operation of the chemical laboratory. (b) The...

  5. 46 CFR 194.15-3 - Responsibility.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194... scientific party embarked may supervise the safety and operation of the chemical laboratory. (b) The...

  6. 46 CFR 194.90-1 - Requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Vessels Contracted for Prior to March 1, 1968 § 194.90-1 Requirements. (a) Vessels contracted for prior to March 1, 1968, shall meet the following...

  7. Decay from the superdeformed bands in {sup 194}Hg

    SciTech Connect

    Henry, R.G.; Khoo, T.L.; Carpenter, M.P.

    1995-08-01

    Superdeformed bands in {sup 194}H g were studied using the early implementation of Gammasphere. The response functions for the Ge detectors were measured for the first time as part of this experiment. Experiments were performed with both a backed target (where the residue stopped in the Au backing) and a thin target (where the residue recoiled into vacuum). This will permit measurements of the decay times of the quasicontinuum {gamma}rays. The spectrum in coincidence with the yrast SD band in {sup 194}Hg reveals the same features as found in the quasicontinuum structure in {sup 192}Hg. These features include: statistical {gamma}rays feeding the SD band, a pronounced E2 peak from transitions feeding the SD band, a Ml/E2 bump at low energies that is associated with the last stages of feeding of the superdeformed band, and a quasicontinuous distribution from {gamma}rays linking SD and normal states, including a sizable clustering of strength around 1.7 MeV. The remarkable similarity of the spectra coincident with SD bands in {sup 192,194}Hg provides additional support for a statistical process for decay out of the SD states. This similarity contrasts with differences observed in the spectrum coincident with the SD band in the odd-even {sup 191}Hg, confirming the predictions about the role of pairing (in normal states) in influencing the shape of the decay-out spectrum.

  8. 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.

  9. 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.

  10. {alpha} decay of {sup 194}At

    SciTech Connect

    Andreyev, A. N.; Antalic, S.; Streicher, B.; Saro, S.; Venhart, M.; Ackermann, D.; Heinz, S.; Hessberger, F. P.; Kojouharov, I.; Kindler, B.; Lommel, B.; Mann, R.; Sulignano, B.; Bianco, L.; Page, R. D.; Sapple, P.; Thomson, J.; Franchoo, S.; Hofmann, S.; Huyse, M.

    2009-06-15

    Detailed {alpha}-decay studies of the neutron-deficient isotope {sup 194}At have been performed in the complete fusion reaction {sup 56}Fe+{sup 141}Pr{yields}{sup 194}At+3n at the velocity filter SHIP. Two {alpha}-decaying isomeric states with half-lives of T{sub 1/2}({sup 194}At{sup m1})=310(8) ms and T{sub 1/2}({sup 194}At{sup m2})=253(10) ms were identified in this nucleus. Their complex decays to the states in the daughter nucleus {sup 190}Bi are discussed in the article. We propose that similar to the case of the neighboring {sup 191,192,193,195}At isotopes, the oblate-deformed configurations based on the proton 1/2{sup +}[440] and/or 7/2{sup -}[514] Nilsson orbitals become important in {sup 194}At. A new isomeric state with the half-life of 175(8) ns was observed in {sup 190}Bi.

  11. 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

  12. 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).

  13. 40 CFR 194.42 - Monitoring.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40... § 194.42 Monitoring. (a) The Department shall conduct an analysis of the effects of disposal system...

  14. 40 CFR 194.44 - Engineered barriers.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 194.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... impact on worker exposure to radiation both during and after incorporation of engineered barriers; (iii...

  15. 40 CFR 194.42 - Monitoring.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40... § 194.42 Monitoring. (a) The Department shall conduct an analysis of the effects of disposal system...

  16. 40 CFR 194.42 - Monitoring.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40... § 194.42 Monitoring. (a) The Department shall conduct an analysis of the effects of disposal system...

  17. 40 CFR 194.44 - Engineered barriers.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 194.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... impact on worker exposure to radiation both during and after incorporation of engineered barriers; (iii...

  18. 40 CFR 194.44 - Engineered barriers.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 194.44 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... impact on worker exposure to radiation both during and after incorporation of engineered barriers; (iii...

  19. 46 CFR 194.15-5 - Ventilation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194... be equipped with acceptable flame screens. (b) Chemical laboratories shall be equipped with power...) Ventilation of air conditioning systems serving the chemical laboratory shall be designed so that air cannot...

  20. 46 CFR 194.15-1 - General.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-1 General. (a) Chemical and scientific laboratories shall be considered service areas, and as such shall be... surfaces where chemical stores are used shall be of incombustible material. (2) Combustible materials may...

  1. 46 CFR 194.15-1 - General.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-1 General. (a) Chemical and scientific laboratories shall be considered service areas, and as such shall be... surfaces where chemical stores are used shall be of incombustible material. (2) Combustible materials may...

  2. 46 CFR 194.05-1 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Stowage and Marking § 194.05-1 General. (a) The master shall be held responsible for and shall require the proper handling, stowage, and marking of all chemical stores and reagents. (b) Chemical stores shall be stowed in a chemical storeroom in approved drums, barrels, or...

  3. 46 CFR 194.20-1 - General.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... shall be made for the containment and removal of chemical spills. (d) Chemical reactions and experiments... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemical Stores and/or Storerooms § 194.20-1 General. (a) The chemical storerooms shall be considered to be service areas and as such shall be subject to the applicable...

  4. 46 CFR 194.20-1 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... shall be made for the containment and removal of chemical spills. (d) Chemical reactions and experiments... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemical Stores and/or Storerooms § 194.20-1 General. (a) The chemical storerooms shall be considered to be service areas and as such shall be subject to the applicable...

  5. 46 CFR 194.20-1 - General.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... shall be made for the containment and removal of chemical spills. (d) Chemical reactions and experiments... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemical Stores and/or Storerooms § 194.20-1 General. (a) The chemical storerooms shall be considered to be service areas and as such shall be subject to the applicable...

  6. 46 CFR 194.20-1 - General.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... shall be made for the containment and removal of chemical spills. (d) Chemical reactions and experiments... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemical Stores and/or Storerooms § 194.20-1 General. (a) The chemical storerooms shall be considered to be service areas and as such shall be subject to the applicable...

  7. 46 CFR 194.20-1 - General.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... shall be made for the containment and removal of chemical spills. (d) Chemical reactions and experiments... EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemical Stores and/or Storerooms § 194.20-1 General. (a) The chemical storerooms shall be considered to be service areas and as such shall be subject to the applicable...

  8. 46 CFR 194.10-25 - Ventilation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-25 Ventilation. (a) Integral magazines. (1) All integral magazines shall be provided with natural or mechanical ventilation. Design calculations shall be submitted demonstrating that the system has sufficient capacity to maintain the...

  9. 46 CFR 194.10-35 - Labeling.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-35 Labeling. (a) Labeling shall be... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY KEEP DOOR CLOSED REMOVE MATCHES AND LIGHTERS PRIOR TO ENTERING (c) Magazine chests shall be marked in...

  10. 46 CFR 194.10-1 - Application.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-1 Application. (a) The provisions of this subpart apply to the construction of integral magazines, magazine vans, and magazine chests... construction of magazines shall be in accordance with the applicable provisions of 49 CFR parts 173 and 176...

  11. 46 CFR 194.10-1 - Application.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-1 Application. (a) The provisions of this subpart apply to the construction of integral magazines, magazine vans, and magazine chests... construction of magazines shall be in accordance with the applicable provisions of 49 CFR parts 173 and 176...

  12. 46 CFR 194.10-1 - Application.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-1 Application. (a) The provisions of this subpart apply to the construction of integral magazines, magazine vans, and magazine chests... construction of magazines shall be in accordance with the applicable provisions of 49 CFR parts 173 and 176...

  13. 46 CFR 194.10-35 - Labeling.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-35 Labeling. (a) Labeling shall be... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY KEEP DOOR CLOSED REMOVE MATCHES AND LIGHTERS PRIOR TO ENTERING (c) Magazine chests shall be marked in...

  14. 46 CFR 194.10-1 - Application.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-1 Application. (a) The provisions of this subpart apply to the construction of integral magazines, magazine vans, and magazine chests... construction of magazines shall be in accordance with the applicable provisions of 49 CFR parts 173 and 176...

  15. 46 CFR 194.10-25 - Ventilation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-25 Ventilation. (a) Integral magazines. (1) All integral magazines shall be provided with natural or mechanical ventilation. Design calculations shall be submitted demonstrating that the system has sufficient capacity to maintain the...

  16. 46 CFR 194.10-35 - Labeling.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-35 Labeling. (a) Labeling shall be... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY KEEP DOOR CLOSED REMOVE MATCHES AND LIGHTERS PRIOR TO ENTERING (c) Magazine chests shall be marked in...

  17. 46 CFR 194.10-35 - Labeling.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-35 Labeling. (a) Labeling shall be... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY KEEP DOOR CLOSED REMOVE MATCHES AND LIGHTERS PRIOR TO ENTERING (c) Magazine chests shall be marked in...

  18. 46 CFR 194.10-35 - Labeling.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-35 Labeling. (a) Labeling shall be... door to magazines and magazine vans shall bear the inscription: MAGAZINE KEEP OPEN LIGHTS AND FIRE AWAY KEEP DOOR CLOSED REMOVE MATCHES AND LIGHTERS PRIOR TO ENTERING (c) Magazine chests shall be marked in...

  19. 46 CFR 194.10-25 - Ventilation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-25 Ventilation. (a) Integral magazines. (1) All integral magazines shall be provided with natural or mechanical ventilation. Design calculations shall be submitted demonstrating that the system has sufficient capacity to maintain the...

  20. 46 CFR 194.10-25 - Ventilation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-25 Ventilation. (a) Integral magazines. (1) All integral magazines shall be provided with natural or mechanical ventilation. Design calculations shall be submitted demonstrating that the system has sufficient capacity to maintain the...

  1. 46 CFR 194.10-25 - Ventilation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-25 Ventilation. (a) Integral magazines. (1) All integral magazines shall be provided with natural or mechanical ventilation. Design calculations shall be submitted demonstrating that the system has sufficient capacity to maintain the...

  2. 46 CFR 194.01-1 - General.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF..., with the exception of subpart 194.90, shall apply to all vessels other than non-self-propelled vessels of less than 300 gross tons contracted for on or after March 1, 1968. (b) Non-self-propelled vessels...

  3. 46 CFR 194.10-1 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-1 Application. (a) The provisions of this subpart apply to the construction of integral magazines, magazine vans, and magazine chests... construction of magazines shall be in accordance with the applicable provisions of 49 CFR parts 173 and 176 and...

  4. 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.

  5. 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.

  6. 46 CFR 194.05-3 - Chemical stores.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Chemical stores. 194.05-3 Section 194.05-3 Shipping..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Stowage and Marking § 194.05-3 Chemical stores. (a) Chemical stores are those chemicals which possess one or more of the following properties...

  7. 46 CFR 194.05-3 - Chemical stores.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Chemical stores. 194.05-3 Section 194.05-3 Shipping..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Stowage and Marking § 194.05-3 Chemical stores. (a) Chemical stores are those chemicals which possess one or more of the following properties...

  8. 46 CFR 194.15-11 - Flushing systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Flushing systems. 194.15-11 Section 194.15-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE... § 194.15-11 Flushing systems. (a) Working spaces in which chemical stores are used shall be equipped...

  9. 46 CFR 194.15-11 - Flushing systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Flushing systems. 194.15-11 Section 194.15-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE... § 194.15-11 Flushing systems. (a) Working spaces in which chemical stores are used shall be equipped...

  10. 40 CFR 194.46 - Removal of waste.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Removal of waste. 194.46 Section 194... PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Assurance Requirements § 194.46 Removal of waste. Any compliance application shall include...

  11. 40 CFR 194.46 - Removal of waste.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Removal of waste. 194.46 Section 194.46... FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE 40... § 194.46 Removal of waste. Any compliance application shall include documentation which...

  12. 46 CFR 194.05-3 - Chemical stores.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Stowage and Marking § 194.05-3 Chemical stores. (a) Chemical stores are those chemicals which possess one or more of the following properties and... 46 Shipping 7 2010-10-01 2010-10-01 false Chemical stores. 194.05-3 Section 194.05-3...

  13. 50 CFR 622.194 - Adjustment of management measures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 12 2013-10-01 2013-10-01 false Adjustment of management measures. 622.194 Section 622.194 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND... ATLANTIC Snapper-Grouper Fishery of the South Atlantic Region § 622.194 Adjustment of management measures...

  14. 12 CFR 194.802 - Description of business.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 1 2012-01-01 2012-01-01 false Description of business. 194.802 Section 194.802 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY SECURITIES OF FEDERAL SAVINGS ASSOCIATIONS Interpretations § 194.802 Description of business. (a) This section applies to the...

  15. 12 CFR 194.802 - Description of business.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 1 2013-01-01 2013-01-01 false Description of business. 194.802 Section 194.802 Banks and Banking COMPTROLLER OF THE CURRENCY, DEPARTMENT OF THE TREASURY SECURITIES OF FEDERAL SAVINGS ASSOCIATIONS Interpretations § 194.802 Description of business. (a) This section applies to the...

  16. 46 CFR 194.15-7 - Fire protection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Fire protection. 194.15-7 Section 194.15-7 Shipping... § 194.15-7 Fire protection. (a) If a fixed or semiportable fire-fighting system is installed, it shall meet the applicable requirements in part 193 of this subchapter. Other fire-fighting systems will...

  17. 46 CFR 194.15-7 - Fire protection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Fire protection. 194.15-7 Section 194.15-7 Shipping... § 194.15-7 Fire protection. (a) If a fixed or semiportable fire-fighting system is installed, it shall meet the applicable requirements in part 193 of this subchapter. Other fire-fighting systems will...

  18. 40 CFR 194.55 - Results of compliance assessments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... effective doses received from all pathways pursuant to § 194.51 and § 194.52; (2) Estimated radionuclide concentrations in USDWs pursuant to § 194.53; and (3) Estimated dose equivalent received from USDWs pursuant to... shall be large enough such that the maximum estimates of doses and concentrations generated exceed...

  19. 40 CFR 194.55 - Results of compliance assessments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... effective doses received from all pathways pursuant to § 194.51 and § 194.52; (2) Estimated radionuclide concentrations in USDWs pursuant to § 194.53; and (3) Estimated dose equivalent received from USDWs pursuant to... shall be large enough such that the maximum estimates of doses and concentrations generated exceed...

  20. 40 CFR 264.194 - General operating requirements.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....194 Section 264.194 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR OWNERS AND OPERATORS OF HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Tank Systems § 264.194 General operating requirements. (a) Hazardous wastes or treatment reagents must...

  1. 46 CFR 194.05-7 - Explosives-Detail requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Explosives-Detail requirements. 194.05-7 Section 194.05... HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Stowage and Marking § 194.05-7 Explosives—Detail requirements. (a) Except as otherwise provided by this part, Division 1.1 and...

  2. 46 CFR 194.05-7 - Explosives-Detail requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Explosives-Detail requirements. 194.05-7 Section 194.05... HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Stowage and Marking § 194.05-7 Explosives—Detail requirements. (a) Except as otherwise provided by this part, Division 1.1 and...

  3. 47 CFR 95.194 - (FRS Rule 4) FRS units.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 5 2010-10-01 2010-10-01 false (FRS Rule 4) FRS units. 95.194 Section 95.194 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PERSONAL RADIO SERVICES Family Radio Service (FRS) General Provisions § 95.194 (FRS Rule 4) FRS units. (a) You may...

  4. 40 CFR 194.46 - Removal of waste.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Removal of waste. 194.46 Section 194... PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Assurance Requirements § 194.46 Removal of waste. Any compliance application shall include documentation...

  5. 46 CFR 194.10-10 - Integral magazine construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Integral magazine construction. 194.10-10 Section 194.10... HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-10 Integral magazine construction. (a) Magazines shall be of permanent watertight construction. Bulkheads and...

  6. 46 CFR 194.10-20 - Magazine chest construction.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Magazine chest construction. 194.10-20 Section 194.10-20..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-20 Magazine chest construction. (a) Magazine chests shall be of watertight metal construction with flush interior. The body...

  7. 46 CFR 194.10-20 - Magazine chest construction.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Magazine chest construction. 194.10-20 Section 194.10-20..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-20 Magazine chest construction. (a) Magazine chests shall be of watertight metal construction with flush interior. The body...

  8. 46 CFR 194.10-30 - Magazine sprinklers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Magazine sprinklers. 194.10-30 Section 194.10-30..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-30 Magazine sprinklers... shall be installed in each magazine or magazine group. The control valve shall generally be...

  9. 46 CFR 194.10-15 - Magazine van construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Magazine van construction. 194.10-15 Section 194.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-15 Magazine...

  10. 46 CFR 194.10-15 - Magazine van construction.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Magazine van construction. 194.10-15 Section 194.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-15 Magazine...

  11. 46 CFR 194.10-20 - Magazine chest construction.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Magazine chest construction. 194.10-20 Section 194.10-20..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-20 Magazine chest construction. (a) Magazine chests shall be of watertight metal construction with flush interior. The body...

  12. 46 CFR 194.10-15 - Magazine van construction.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Magazine van construction. 194.10-15 Section 194.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-15 Magazine...

  13. 46 CFR 194.10-15 - Magazine van construction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Magazine van construction. 194.10-15 Section 194.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-15 Magazine...

  14. 46 CFR 194.10-20 - Magazine chest construction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Magazine chest construction. 194.10-20 Section 194.10-20..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-20 Magazine chest construction. (a) Magazine chests shall be of watertight metal construction with flush interior. The body...

  15. 46 CFR 194.10-20 - Magazine chest construction.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Magazine chest construction. 194.10-20 Section 194.10-20..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-20 Magazine chest construction. (a) Magazine chests shall be of watertight metal construction with flush interior. The body...

  16. 46 CFR 194.10-30 - Magazine sprinklers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Magazine sprinklers. 194.10-30 Section 194.10-30..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-30 Magazine sprinklers... shall be installed in each magazine or magazine group. The control valve shall generally be...

  17. 46 CFR 194.10-10 - Integral magazine construction.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Integral magazine construction. 194.10-10 Section 194.10... HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-10 Integral magazine construction. (a) Magazines shall be of permanent watertight construction. Bulkheads and...

  18. 46 CFR 194.10-30 - Magazine sprinklers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Magazine sprinklers. 194.10-30 Section 194.10-30..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-30 Magazine sprinklers... shall be installed in each magazine or magazine group. The control valve shall generally be...

  19. 46 CFR 194.10-10 - Integral magazine construction.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Integral magazine construction. 194.10-10 Section 194.10... HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-10 Integral magazine construction. (a) Magazines shall be of permanent watertight construction. Bulkheads and...

  20. 46 CFR 194.10-10 - Integral magazine construction.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Integral magazine construction. 194.10-10 Section 194.10... HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-10 Integral magazine construction. (a) Magazines shall be of permanent watertight construction. Bulkheads and...

  1. 46 CFR 194.10-30 - Magazine sprinklers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Magazine sprinklers. 194.10-30 Section 194.10-30..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-30 Magazine sprinklers... shall be installed in each magazine or magazine group. The control valve shall generally be...

  2. 46 CFR 194.10-15 - Magazine van construction.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Magazine van construction. 194.10-15 Section 194.10-15 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-15 Magazine...

  3. 46 CFR 194.10-10 - Integral magazine construction.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Integral magazine construction. 194.10-10 Section 194.10... HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-10 Integral magazine construction. (a) Magazines shall be of permanent watertight construction. Bulkheads and...

  4. 7 CFR 4280.194-4280.199 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false 4280.194-4280.199 Section 4280.194-4280.199 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND... Efficiency Improvements Program Section D. Combined Funding §§ 4280.194-4280.199...

  5. 46 CFR 194.10-30 - Magazine sprinklers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Magazine sprinklers. 194.10-30 Section 194.10-30..., USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-30 Magazine sprinklers... shall be installed in each magazine or magazine group. The control valve shall generally be in...

  6. 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/

  7. 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).

  8. 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.

  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. 40 CFR 194.15 - certification application(s).

    Code of Federal Regulations, 2010 CFR

    1996-07-01

    ... 40 PROTECTION OF ENVIRONMENT 12 1996-07-01 1996-07-01 false certification application(s). 194.15 Sec. 194.15 Content of compliance re PROTECTION OF ENVIRONMENT ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S COMPLIANCE WITH THE...

  17. 14 CFR Sec. 19-4 - Service classes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Service classes. Sec. 19-4 Section 19-4 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS Operating Statistics...

  18. 14 CFR Sec. 19-4 - Service classes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Service classes. Sec. 19-4 Section 19-4 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) ECONOMIC REGULATIONS UNIFORM SYSTEM OF ACCOUNTS AND REPORTS FOR LARGE CERTIFICATED AIR CARRIERS Operating Statistics...

  19. 46 CFR 194.20-11 - Flushing systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Flushing systems. 194.20-11 Section 194.20-11 Shipping... Flushing systems. (a) Provision shall be made for flushing away chemical spills. (b) If a drainage system is installed, it shall be separate from any other drainage system. ...

  20. 46 CFR 194.20-11 - Flushing systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Flushing systems. 194.20-11 Section 194.20-11 Shipping... Flushing systems. (a) Provision shall be made for flushing away chemical spills. (b) If a drainage system is installed, it shall be separate from any other drainage system. ...

  1. 46 CFR 194.20-11 - Flushing systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Flushing systems. 194.20-11 Section 194.20-11 Shipping... Flushing systems. (a) Provision shall be made for flushing away chemical spills. (b) If a drainage system is installed, it shall be separate from any other drainage system. ...

  2. 38 CFR 19.4 - Principal functions of the Board.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2011-07-01 2011-07-01 false Principal functions of the Board. 19.4 Section 19.4 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....4 Principal functions of the Board. The principal functions of the Board are to make determinations...

  3. 38 CFR 19.4 - Principal functions of the Board.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 2 2010-07-01 2010-07-01 false Principal functions of the Board. 19.4 Section 19.4 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS....4 Principal functions of the Board. The principal functions of the Board are to make determinations...

  4. 34 CFR 403.194 - What are the comparability requirements?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 3 2011-07-01 2011-07-01 false What are the comparability requirements? 403.194 Section 403.194 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION...

  5. 46 CFR 194.20-11 - Flushing systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Flushing systems. 194.20-11 Section 194.20-11 Shipping... Flushing systems. (a) Provision shall be made for flushing away chemical spills. (b) If a drainage system is installed, it shall be separate from any other drainage system. ...

  6. 27 CFR 41.194 - Articles of partnership or association.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2012-04-01 2011-04-01 true Articles of partnership or association. 41.194 Section 41.194 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY (CONTINUED) TOBACCO IMPORTATION OF TOBACCO PRODUCTS, CIGARETTE PAPERS...

  7. 46 CFR 194.20-19 - Piping and electrical requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Piping and electrical requirements. 194.20-19 Section... Storerooms § 194.20-19 Piping and electrical requirements. (a) Piping, electrical equipment, and wiring shall... storeroom itself. (b) The electrical installation shall be in accordance with the applicable requirements of...

  8. 46 CFR 194.20-19 - Piping and electrical requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Piping and electrical requirements. 194.20-19 Section... Storerooms § 194.20-19 Piping and electrical requirements. (a) Piping, electrical equipment, and wiring shall... storeroom itself. (b) The electrical installation shall be in accordance with the applicable requirements of...

  9. 46 CFR 194.20-17 - Compressed gases.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Compressed gases. 194.20-17 Section 194.20-17 Shipping... Compressed gases. (a) Nonflammable compressed gases (excluding oxygen) may be securely stowed in the... chemical storeroom. (b) Flammable compressed gases and oxygen shall be stowed in accordance with 49 CFR...

  10. 46 CFR 194.20-17 - Compressed gases.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Compressed gases. 194.20-17 Section 194.20-17 Shipping... Compressed gases. (a) Nonflammable compressed gases (excluding oxygen) may be securely stowed in the... chemical storeroom. (b) Flammable compressed gases and oxygen shall be stowed in accordance with 49 CFR...

  11. 46 CFR 194.20-17 - Compressed gases.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Compressed gases. 194.20-17 Section 194.20-17 Shipping... Compressed gases. (a) Nonflammable compressed gases (excluding oxygen) may be securely stowed in the... chemical storeroom. (b) Flammable compressed gases and oxygen shall be stowed in accordance with 49 CFR...

  12. 46 CFR 194.20-17 - Compressed gases.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Compressed gases. 194.20-17 Section 194.20-17 Shipping... Compressed gases. (a) Nonflammable compressed gases (excluding oxygen) may be securely stowed in the... chemical storeroom. (b) Flammable compressed gases and oxygen shall be stowed in accordance with 49 CFR...

  13. 49 CFR 173.194 - Gas identification sets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 2 2012-10-01 2012-10-01 false Gas identification sets. 173.194 Section 173.194... Gas identification sets. Gas identification sets containing poisonous material must be packaged in... silical gel, gas identification sets may be shipped as follows: (1) If the poisonous material does not...

  14. 46 CFR 194.20-17 - Compressed gases.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Compressed gases. 194.20-17 Section 194.20-17 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemical Stores and/or Storerooms §...

  15. 46 CFR 194.20-7 - Fire protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Fire protection. 194.20-7 Section 194.20-7 Shipping... Fire protection. (a) Each chemical storeroom shall be protected by a fixed automatic carbon dioxide... fire extinguishers are required in accordance with Table 193.50-10(a) of this subchapter. ...

  16. 46 CFR 194.20-7 - Fire protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Fire protection. 194.20-7 Section 194.20-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE... system using carbon dioxide or a clean agent complying with 46 CFR subpart 95.16, installed in accordance...

  17. 40 CFR 194.5 - Publications incorporated by reference.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) American Society of Mechanical Engineers (ASME) Nuclear Quality Assurance (NQA) Standard, NQA-1-1989...) ASME NQA-2a-1990 addenda, part 2.7, to ASME NQA-2-1989 edition “Quality Assurance Requirements for Nuclear Facility Applications;” IBR approved for § 194.22 and § 194.23. (4) ASME NQA-3-1989...

  18. 46 CFR 194.20-19 - Piping and electrical requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Piping and electrical requirements. 194.20-19 Section... Storerooms § 194.20-19 Piping and electrical requirements. (a) Piping, electrical equipment, and wiring shall... storeroom itself. (b) The electrical installation shall be in accordance with the applicable requirements...

  19. 46 CFR 194.20-19 - Piping and electrical requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Piping and electrical requirements. 194.20-19 Section... Storerooms § 194.20-19 Piping and electrical requirements. (a) Piping, electrical equipment, and wiring shall... storeroom itself. (b) The electrical installation shall be in accordance with the applicable requirements...

  20. 46 CFR 194.20-19 - Piping and electrical requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Piping and electrical requirements. 194.20-19 Section... Storerooms § 194.20-19 Piping and electrical requirements. (a) Piping, electrical equipment, and wiring shall... storeroom itself. (b) The electrical installation shall be in accordance with the applicable requirements...

  1. 10 CFR 205.194 - Participants; official service list.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 3 2011-01-01 2011-01-01 false Participants; official service list. 205.194 Section 205.194 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable... directed, his address and the products, dollar amounts, time period, and geographical area specified in...

  2. 10 CFR 205.194 - Participants; official service list.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 3 2013-01-01 2013-01-01 false Participants; official service list. 205.194 Section 205.194 Energy DEPARTMENT OF ENERGY OIL ADMINISTRATIVE PROCEDURES AND SANCTIONS Notice of Probable... directed, his address and the products, dollar amounts, time period, and geographical area specified in...

  3. 40 CFR 194.41 - Active institutional controls.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... controls and their effectiveness in terms of preventing or reducing radionuclide releases shall be... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Active institutional controls. 194.41... Assurance Requirements § 194.41 Active institutional controls. (a) Any compliance application shall...

  4. 46 CFR 194.15-7 - Fire protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Fire protection. 194.15-7 Section 194.15-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory...

  5. 40 CFR 194.64 - Documentation of continued compliance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Documentation of continued compliance. 194.64 Section 194.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  6. 40 CFR 194.12 - Submission of compliance applications.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Submission of compliance applications. 194.12 Section 194.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  7. 40 CFR 194.41 - Active institutional controls.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Active institutional controls. 194.41 Section 194.41 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  8. 40 CFR 194.13 - Submission of reference materials.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Submission of reference materials. 194.13 Section 194.13 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  9. 40 CFR 194.64 - Documentation of continued compliance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Documentation of continued compliance. 194.64 Section 194.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  10. 40 CFR 194.31 - Application of release limits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Application of release limits. 194.31 Section 194.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  11. 40 CFR 194.34 - Results of performance assessments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Results of performance assessments. 194.34 Section 194.34 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  12. 40 CFR 194.63 - Final rule for certification.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Final rule for certification. 194.63 Section 194.63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  13. 40 CFR 194.46 - Removal of waste.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Removal of waste. 194.46 Section 194.46 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  14. 40 CFR 194.63 - Final rule for certification.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Final rule for certification. 194.63 Section 194.63 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  15. 40 CFR 194.41 - Active institutional controls.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Active institutional controls. 194.41 Section 194.41 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  16. 40 CFR 194.31 - Application of release limits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Application of release limits. 194.31 Section 194.31 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S...

  17. 46 CFR 194.20-7 - Fire protection.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Fire protection. 194.20-7 Section 194.20-7 Shipping... Fire protection. (a) Each chemical storeroom must be protected by a fixed automatic extinguishing... with 46 CFR subpart 193.15. (b) Portable fire extinguishers are required in accordance with Table...

  18. 46 CFR 194.20-7 - Fire protection.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Fire protection. 194.20-7 Section 194.20-7 Shipping... Fire protection. (a) Each chemical storeroom shall be protected by a fixed automatic carbon dioxide... fire extinguishers are required in accordance with Table 193.50-10(a) of this subchapter....

  19. 46 CFR 194.20-7 - Fire protection.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Fire protection. 194.20-7 Section 194.20-7 Shipping... Fire protection. (a) Each chemical storeroom must be protected by a fixed automatic extinguishing... with 46 CFR subpart 193.15. (b) Portable fire extinguishers are required in accordance with Table...

  20. 40 CFR 194.23 - Models and computer codes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Models and computer codes. 194.23... General Requirements § 194.23 Models and computer codes. (a) Any compliance application shall include: (1... obtain stable solutions; (iv) Computer models accurately implement the numerical models; i.e., computer...

  1. 40 CFR 194.23 - Models and computer codes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Models and computer codes. 194.23... General Requirements § 194.23 Models and computer codes. (a) Any compliance application shall include: (1... obtain stable solutions; (iv) Computer models accurately implement the numerical models; i.e., computer...

  2. 40 CFR 194.23 - Models and computer codes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Models and computer codes. 194.23... General Requirements § 194.23 Models and computer codes. (a) Any compliance application shall include: (1... obtain stable solutions; (iv) Computer models accurately implement the numerical models; i.e., computer...

  3. 13 CFR 120.194 - Use of computer forms.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Use of computer forms. 120.194... Applying to All Business Loans Computerized Sba Forms § 120.194 Use of computer forms. Any Applicant or Participant may use computer generated SBA application forms, closing forms, and other forms designated by SBA...

  4. 13 CFR 120.194 - Use of computer forms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Use of computer forms. 120.194... Applying to All Business Loans Computerized Sba Forms § 120.194 Use of computer forms. Any Applicant or Participant may use computer generated SBA application forms, closing forms, and other forms designated by SBA...

  5. 13 CFR 120.194 - Use of computer forms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Use of computer forms. 120.194... Applying to All Business Loans Computerized Sba Forms § 120.194 Use of computer forms. Any Applicant or Participant may use computer generated SBA application forms, closing forms, and other forms designated by SBA...

  6. 40 CFR 194.23 - Models and computer codes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Models and computer codes. 194.23... General Requirements § 194.23 Models and computer codes. (a) Any compliance application shall include: (1... obtain stable solutions; (iv) Computer models accurately implement the numerical models; i.e., computer...

  7. 13 CFR 120.194 - Use of computer forms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Use of computer forms. 120.194... Applying to All Business Loans Computerized Sba Forms § 120.194 Use of computer forms. Any Applicant or Participant may use computer generated SBA application forms, closing forms, and other forms designated by SBA...

  8. 13 CFR 120.194 - Use of computer forms.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Use of computer forms. 120.194... Applying to All Business Loans Computerized Sba Forms § 120.194 Use of computer forms. Any Applicant or Participant may use computer generated SBA application forms, closing forms, and other forms designated by SBA...

  9. 40 CFR 194.23 - Models and computer codes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Models and computer codes. 194.23... General Requirements § 194.23 Models and computer codes. (a) Any compliance application shall include: (1... obtain stable solutions; (iv) Computer models accurately implement the numerical models; i.e., computer...

  10. 46 CFR 194.15-11 - Flushing systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Flushing systems. 194.15-11 Section 194.15-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory...

  11. 46 CFR 194.15-11 - Flushing systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Flushing systems. 194.15-11 Section 194.15-11 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory...

  12. 46 CFR 194.15-7 - Fire protection.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Fire protection. 194.15-7 Section 194.15-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory...

  13. 46 CFR 194.15-7 - Fire protection.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Fire protection. 194.15-7 Section 194.15-7 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING, USE, AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory...

  14. 21 CFR 1.94 - Hearing on refusal of admission.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Hearing on refusal of admission. 1.94 Section 1.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL... written notice to that effect, stating the reasons therefor. The notice shall specify a place and a...

  15. 21 CFR 1.94 - Hearing on refusal of admission.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Hearing on refusal of admission. 1.94 Section 1.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL GENERAL... written notice to that effect, stating the reasons therefor. The notice shall specify a place and a...

  16. 34 CFR 403.194 - What are the comparability requirements?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 34 Education 3 2012-07-01 2012-07-01 false What are the comparability requirements? 403.194 Section 403.194 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF VOCATIONAL AND ADULT EDUCATION, DEPARTMENT OF EDUCATION STATE VOCATIONAL AND APPLIED TECHNOLOGY EDUCATION...

  17. 26 CFR 1.194-1 - Amortization of reforestation expenditures.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 3 2014-04-01 2014-04-01 false Amortization of reforestation expenditures. 1... (continued) § 1.194-1 Amortization of reforestation expenditures. (a) In general. Section 194 allows a taxpayer to elect to amortize over an 84-month period, up to $10,000 of reforestation expenditures (as...

  18. 26 CFR 1.194-1 - Amortization of reforestation expenditures.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Amortization of reforestation expenditures. 1... (continued) § 1.194-1 Amortization of reforestation expenditures. (a) In general. Section 194 allows a taxpayer to elect to amortize over an 84-month period, up to $10,000 of reforestation expenditures (as...

  19. 40 CFR 194.46 - Removal of waste.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Removal of waste. 194.46 Section 194.46 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION... mining the sealed disposal system, given technology levels at the time a compliance application...

  20. 40 CFR 194.5 - Publications incorporated by reference.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... 194.5 Section 194.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION.... Nuclear Regulatory Commission, NUREG-1297 “Peer Review for High-Level Nuclear Waste Repositories... Characterization of High-Level Nuclear Waste Repositories” (excluding section 2.1 (b) and (c)); IBR approved...

  1. 46 CFR 194.01-1 - 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. 194.01-1 Section 194.01-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING... effect over State or local regulations in the same field. ...

  2. 46 CFR 194.01-1 - 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. 194.01-1 Section 194.01-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OCEANOGRAPHIC RESEARCH VESSELS HANDLING... effect over State or local regulations in the same field. ...

  3. 26 CFR 1.194-1 - Amortization of reforestation expenditures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Amortization of reforestation expenditures. 1....194-1 Amortization of reforestation expenditures. (a) In general. Section 194 allows a taxpayer to elect to amortize over an 84-month period, up to $10,000 of reforestation expenditures (as defined...

  4. 49 CFR 194.101 - Operators required to submit plans.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... in § 194.103(c) and is not eligible for an exception under § 194.101(b), can be expected to cause... not operate at a maximum operating pressure established under § 195.406 that corresponds to a...

  5. 49 CFR 194.101 - Operators required to submit plans.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... in § 194.103(c) and is not eligible for an exception under § 194.101(b), can be expected to cause... not operate at a maximum operating pressure established under § 195.406 that corresponds to a...

  6. 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.

  7. 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

  8. 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.

  9. 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...

  10. 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...

  11. 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.

  12. 26 CFR 1.194-1 - Amortization of reforestation expenditures.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... property (as defined in § 1.194-3(a)). The election is not available to trusts. Only those reforestation... first day of the first month of the last half of the taxable year during which the taxpayer incurs...

  13. 26 CFR 1.194-1 - Amortization of reforestation expenditures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... property (as defined in § 1.194-3(a)). The election is not available to trusts. Only those reforestation... first day of the first month of the last half of the taxable year during which the taxpayer incurs...

  14. 40 CFR 194.55 - Results of compliance assessments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.55 Results of compliance assessments. (a...

  15. 40 CFR 194.51 - Consideration of protected individual.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.51 Consideration of protected individual...

  16. 40 CFR 194.55 - Results of compliance assessments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.55 Results of compliance assessments. (a...

  17. 40 CFR 194.51 - Consideration of protected individual.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.51 Consideration of protected individual...

  18. 40 CFR 194.55 - Results of compliance assessments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.55 Results of compliance assessments. (a...

  19. 40 CFR 194.51 - Consideration of protected individual.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.51 Consideration of protected individual...

  20. 40 CFR 417.194 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars and Cakes Subcategory § 417.194 Pretreatment standards for existing sources. Any existing...

  1. 40 CFR 417.194 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars and Cakes Subcategory § 417.194 Pretreatment standards for existing sources. Any existing...

  2. 40 CFR 417.194 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars and Cakes Subcategory § 417.194 Pretreatment standards for existing sources. Any existing...

  3. 40 CFR 417.194 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars and Cakes Subcategory § 417.194 Pretreatment standards for existing sources. Any existing...

  4. 40 CFR 417.194 - Pretreatment standards for existing sources.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) EFFLUENT GUIDELINES AND STANDARDS SOAP AND DETERGENT MANUFACTURING POINT SOURCE CATEGORY Manufacture of Detergent Bars and Cakes Subcategory § 417.194 Pretreatment standards for existing sources. Any existing...

  5. 40 CFR 194.51 - Consideration of protected individual.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.51 Consideration of protected...

  6. 40 CFR 194.51 - Consideration of protected individual.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.51 Consideration of protected...

  7. 49 CFR 194.109 - Submission of state response plans.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PLANS FOR ONSHORE OIL PIPELINES Response Plans § 194.109 Submission of state response plans. (a) In lieu...); and (3) Ensure through contract or other approved means the necessary private personnel and equipment...

  8. 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.

  9. 49 CFR 173.194 - Gas identification sets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... exceed 5 mL (0.2 fluid ounce) if a liquid or 5 g (0.2 ounce) if a solid, it may be packed in glass inner...L (0.2 fluid ounce) if a liquid or 20 g (0.7 ounce) if a solid, it may be packed in glass inner... 49 Transportation 2 2011-10-01 2011-10-01 false Gas identification sets. 173.194 Section 173.194...

  10. 49 CFR 173.194 - Gas identification sets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... exceed 5 mL (0.2 fluid ounce) if a liquid or 5 g (0.2 ounce) if a solid, it may be packed in glass inner... material does not exceed 5 mL (0.2 fluid ounce) if a liquid or 20 g (0.7 ounce) if a solid, it may be... 49 Transportation 2 2013-10-01 2013-10-01 false Gas identification sets. 173.194 Section 173.194...

  11. 49 CFR 173.194 - Gas identification sets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... exceed 5 mL (0.2 fluid ounce) if a liquid or 5 g (0.2 ounce) if a solid, it may be packed in glass inner...L (0.2 fluid ounce) if a liquid or 20 g (0.7 ounce) if a solid, it may be packed in glass inner... 49 Transportation 2 2010-10-01 2010-10-01 false Gas identification sets. 173.194 Section 173.194...

  12. 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.

  13. Overexpression of OsCYP19-4 increases tolerance to cold stress and enhances grain yield in rice (Oryza sativa).

    PubMed

    Yoon, Dae Hwa; Lee, Sang Sook; Park, Hyun Ji; Lyu, Jae Il; Chong, Won Seog; Liu, Jang Ryol; Kim, Beom-Gi; Ahn, Jun Cheul; Cho, Hye Sun

    2016-01-01

    AtCYP19-4 (also known as CYP5) was previously identified as interacting in vitro with GNOM, a member of a large family of ARF guanine nucleotide exchange factors that is required for proper polar localization of the auxin efflux carrier PIN1. The present study demonstrated that OsCYP19-4, a gene encoding a putative homologue of AtCYP19-4, was up-regulated by several stresses and showed over 10-fold up-regulation in response to cold. The study further demonstrated that the promoter of OsCYP19-4 was activated in response to cold stress. An OsCYP19-4-GFP fusion protein was targeted to the outside of the plasma membrane via the endoplasmic reticulum as determined using brefeldin A, a vesicle trafficking inhibitor. An in vitro assay with a synthetic substrate oligomer confirmed that OsCYP19-4 had peptidyl-prolyl cis-trans isomerase activity, as was previously reported for AtCYP19-4. Rice plants overexpressing OsCYP19-4 showed cold-resistance phenotypes with significantly increased tiller and spike numbers, and consequently enhanced grain weight, compared with wild-type plants. Based on these results, the authors suggest that OsCYP19-4 is required for developmental acclimation to environmental stresses, especially cold. Furthermore, the results point to the potential of manipulating OsCYP19-4 expression to enhance cold tolerance or to increase biomass. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  14. 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.

  15. 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

  16. [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.

  17. 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.

  18. 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.

  19. Binding of bovine T194A PrPC by PrPSc-specific antibodies

    PubMed Central

    Madampage, Claudia A; Määttänen, Pekka; Marciniuk, Kristen; Brownlie, Robert; Andrievskaia, Olga; Potter, Andrew; Cashman, Neil R; Lee, Jeremy S; Napper, Scott

    2013-01-01

    Transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases that are based on the misfolding of a cellular prion protein (PrPC) into an infectious, pathological conformation (PrPSc). There is proof-of-principle evidence that a prion vaccine is possible but this is tempered with concerns of the potential dangers associated with induction of immune responses to a widely-expressed self-protein. By targeting epitopes that are specifically exposed upon protein misfolding, our group developed a vaccine that induces PrPSc-specific antibody responses. Here we consider the ability of this polyclonal antibody (SN6b) to bind to a mutant of PrPC associated with spontaneous prion disease. Polyclonal antibodies were selected to mimic the vaccination outcome and also explore all possible protein conformations of the recombinant bovine prion protein with mutation T194A [bPrP(T194A)]. This mutant is a homolog of the human T183A mutation of PrPC that is associated with early onset of familial dementia. With nanopore analysis, under non-denaturing conditions, we observed binding of the SN6b antibody to bPrP(T194A). This interaction was confirmed through ELISAs as well as immunoprecipitation of the recombinant and cellularly expressed forms of bPrP(T194A). This interaction did not promote formation of a protease resistant conformation of PrP in vitro. Collectively, these findings support the disease-specific approach for immunotherapy of prion diseases but also suggest that the concept of conformation-specific immunotherapy may be complicated in individuals who are genetically predisposed to PrPC misfolding. PMID:23787697

  20. 26 CFR 1.194-4 - Time and manner of making election.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) of this section, an election to amortize reforestation expenditures under section 194 shall be made... property for which reforestation expenditures are being amortized under section 194. The election may only... section 194, the election to amortize reforestation expenditures under section 194 may be made by a...

  1. 26 CFR 1.194-4 - Time and manner of making election.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) of this section, an election to amortize reforestation expenditures under section 194 shall be made... property for which reforestation expenditures are being amortized under section 194. The election may only... section 194, the election to amortize reforestation expenditures under section 194 may be made by a...

  2. 26 CFR 1.194-4 - Time and manner of making election.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) of this section, an election to amortize reforestation expenditures under section 194 shall be made... property for which reforestation expenditures are being amortized under section 194. The election may only... section 194, the election to amortize reforestation expenditures under section 194 may be made by a...

  3. 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

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. 34 CFR 668.194 - Economically disadvantaged appeals.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....194 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS Two Year Cohort Default... student is a married independent student), is less than the amount listed in the Department of Health...

  9. 34 CFR 668.194 - Economically disadvantaged appeals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....194 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS Two Year Cohort Default... student is a married independent student), is less than the amount listed in the Department of Health...

  10. 34 CFR 668.194 - Economically disadvantaged appeals.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....194 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS Two Year Cohort Default... student is a married independent student), is less than the amount listed in the Department of Health...

  11. 34 CFR 668.194 - Economically disadvantaged appeals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....194 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS Two Year Cohort Default... student is a married independent student), is less than the amount listed in the Department of Health...

  12. 34 CFR 668.194 - Economically disadvantaged appeals.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....194 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION STUDENT ASSISTANCE GENERAL PROVISIONS Two Year Cohort Default... student is a married independent student), is less than the amount listed in the Department of Health...

  13. 34 CFR 300.194 - Show cause hearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... DISABILITIES State Eligibility By-Pass for Children in Private Schools § 300.194 Show cause hearing. (a) If a... agency, and other appropriate public and private school officials of the time and place for the hearing... representatives of private schools that they may be represented by legal counsel and submit oral or written...

  14. 40 CFR 194.32 - Scope of performance assessments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....32 Section 194.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... system during the regulatory time frame. (b) Assessments of mining effects may be limited to changes in...

  15. 40 CFR 194.54 - Scope of compliance assessments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Section 194.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... effects on the disposal system of: (1) Existing boreholes in the vicinity of the disposal system, with...

  16. 40 CFR 194.54 - Scope of compliance assessments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....54 Section 194.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... effects on the disposal system of: (1) Existing boreholes in the vicinity of the disposal system, with...

  17. 40 CFR 194.32 - Scope of performance assessments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....32 Section 194.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... system during the regulatory time frame. (b) Assessments of mining effects may be limited to changes in...

  18. 40 CFR 194.32 - Scope of performance assessments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ....32 Section 194.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... system during the regulatory time frame. (b) Assessments of mining effects may be limited to changes in...

  19. 40 CFR 194.32 - Scope of performance assessments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....32 Section 194.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... system during the regulatory time frame. (b) Assessments of mining effects may be limited to changes in...

  20. 40 CFR 194.54 - Scope of compliance assessments.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....54 Section 194.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... effects on the disposal system of: (1) Existing boreholes in the vicinity of the disposal system, with...

  1. 40 CFR 194.54 - Scope of compliance assessments.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....54 Section 194.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... effects on the disposal system of: (1) Existing boreholes in the vicinity of the disposal system, with...

  2. 40 CFR 194.32 - Scope of performance assessments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....32 Section 194.32 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... system during the regulatory time frame. (b) Assessments of mining effects may be limited to changes in...

  3. 40 CFR 194.54 - Scope of compliance assessments.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ....54 Section 194.54 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... effects on the disposal system of: (1) Existing boreholes in the vicinity of the disposal system, with...

  4. 7 CFR 4280.194 - Actions prior to grant closing.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.194 Actions prior to grant closing. Applicants expecting funds from other sources for use in completing projects...

  5. 7 CFR 4280.194 - Actions prior to grant closing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.194 Actions prior to grant closing. Applicants expecting funds from other sources for use in completing projects...

  6. 7 CFR 4280.194 - Actions prior to grant closing.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE LOANS AND GRANTS Rural Energy for America Program General Energy Audit and Renewable Energy Development Assistance Grants § 4280.194 Actions prior to grant closing. Applicants expecting funds from other sources for use in completing projects...

  7. 22 CFR 194.1 - Authority and scope of application.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Section 194.1 Foreign Relations DEPARTMENT OF STATE INTERNATIONAL COMMERCIAL ARBITRATION INTER-AMERICAN... arbitration of certain international commercial disputes to which the Inter-American Convention on International Commercial Arbitration applies. The amended Rules of Procedure are set out in full in appendix A...

  8. 46 CFR 194.15-11 - Flushing systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Chemistry Laboratory and Scientific Laboratory § 194.15-11 Flushing systems. (a) Working spaces in which chemical stores are used shall be equipped with a fresh water supply shower. (b) There shall be a provision for flushing away chemical spills. ...

  9. 40 CFR 19.4 - Penalty adjustment and table.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... MONETARY PENALTIES FOR INFLATION § 19.4 Penalty adjustment and table. The adjusted statutory penalty... Inflation Adjustments U.S. code citation Environmental statute Statutorypenalties, as enacted... amounts set forth in this Table reflect an inflation adjustment to the calendar year 1992 penalty...

  10. 46 CFR 194.05-21 - Other regulated materials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... regulated materials. (a) Other Regulated Materials (DOT Hazard Class “ORM”) as chemical stores and reagents... Regulated Materials (DOT Hazard Class “ORM”) which are not chemical stores and reagents shall be regulated... 46 Shipping 7 2010-10-01 2010-10-01 false Other regulated materials. 194.05-21 Section...

  11. 40 CFR 194.52 - Consideration of exposure pathways.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.52 Consideration of exposure pathways. In... water from any underground source of drinking water in the accessible environment. ...

  12. 40 CFR 194.52 - Consideration of exposure pathways.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.52 Consideration of exposure pathways. In... water from any underground source of drinking water in the accessible environment. ...

  13. 40 CFR 194.52 - Consideration of exposure pathways.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.52 Consideration of exposure pathways. In... water from any underground source of drinking water in the accessible environment. ...

  14. 27 CFR 41.194 - Articles of partnership or association.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Articles of partnership or... AND TUBES, AND PROCESSED TOBACCO Tobacco Products Importers § 41.194 Articles of partnership or..., must furnish with its application for permit required by § 41.191 a true copy of the articles...

  15. 27 CFR 41.194 - Articles of partnership or association.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Articles of partnership or... AND TUBES, AND PROCESSED TOBACCO Tobacco Products Importers § 41.194 Articles of partnership or..., must furnish with its application for permit required by § 41.191 a true copy of the articles...

  16. 27 CFR 41.194 - Articles of partnership or association.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2013-04-01 2013-04-01 false Articles of partnership or... AND TUBES, AND PROCESSED TOBACCO Tobacco Products Importers § 41.194 Articles of partnership or..., must furnish with its application for permit required by § 41.191 a true copy of the articles...

  17. 27 CFR 41.194 - Articles of partnership or association.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2014-04-01 2014-04-01 false Articles of partnership or... AND TUBES, AND PROCESSED TOBACCO Tobacco Products Importers § 41.194 Articles of partnership or... products must furnish with its application for the permit required by § 41.191 a true copy of the...

  18. 38 CFR 17.194 - Aid for domiciliary 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 domiciliary care... Aid to States for Care of Veterans in State Homes § 17.194 Aid for domiciliary care. Aid may be paid to the designated State official for domiciliary care furnished in a recognized State home for...

  19. 40 CFR 60.194 - Monitoring of operations.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Reduction Plants § 60.194 Monitoring of operations. (a) The owner or operator of any affected facility... feed rates, and cell or potline voltages. (c) Following the initial performance test as required under... bake plant. If the owner or operator show that emissions from the primary control system or the...

  20. 40 CFR 60.194 - Monitoring of operations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Reduction Plants § 60.194 Monitoring of operations. (a) The owner or operator of any affected facility... feed rates, and cell or potline voltages. (c) Following the initial performance test as required under... bake plant. If the owner or operator show that emissions from the primary control system or the...

  1. 40 CFR 60.194 - Monitoring of operations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Reduction Plants § 60.194 Monitoring of operations. (a) The owner or operator of any affected facility... feed rates, and cell or potline voltages. (c) Following the initial performance test as required under... bake plant. If the owner or operator show that emissions from the primary control system or the...

  2. 40 CFR 60.194 - Monitoring of operations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Reduction Plants § 60.194 Monitoring of operations. (a) The owner or operator of any affected facility... feed rates, and cell or potline voltages. (c) Following the initial performance test as required under... bake plant. If the owner or operator show that emissions from the primary control system or the...

  3. 40 CFR 60.194 - Monitoring of operations.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Reduction Plants § 60.194 Monitoring of operations. (a) The owner or operator of any affected facility... feed rates, and cell or potline voltages. (c) Following the initial performance test as required under... bake plant. If the owner or operator show that emissions from the primary control system or the...

  4. 49 CFR 194.107 - General response plan requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... summary as required in § 194.113, (ii) Immediate notification procedures, (iii) Spill detection and... support, (vii) Training procedures, (viii) Equipment testing, (ix) Drill program—an operator will satisfy the requirement for a drill program by following the National Preparedness for Response...

  5. 49 CFR 194.107 - General response plan requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... mitigation procedures, (iv) The name, address, and telephone number of the oil spill response organization... PLANS FOR ONSHORE OIL PIPELINES Response Plans § 194.107 General response plan requirements. (a) Each... mitigation or prevention of a substantial threat of a worst case discharge; (ii) Identify environmentally and...

  6. 194. Photocopy of drawing, Twin Falls Canal Company, date unknown. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    194. Photocopy of drawing, Twin Falls Canal Company, date unknown. PROFILE AND GATE PLAN, NORTH ISLAND CROSS SECTION OF DAM, TWIN FALLS COUNTY, MILNER, IDAHO; BLUEPRINT. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  7. 40 CFR 194.52 - Consideration of exposure pathways.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.52 Consideration of exposure pathways. In... water from any underground source of drinking water in the accessible environment....

  8. 40 CFR 194.52 - Consideration of exposure pathways.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROTECTION PROGRAMS CRITERIA FOR THE CERTIFICATION AND RE-CERTIFICATION OF THE WASTE ISOLATION PILOT PLANT'S... Individual and Ground-Water Protection Requirements § 194.52 Consideration of exposure pathways. In... water from any underground source of drinking water in the accessible environment....

  9. 33 CFR 110.194 - Mobile Bay, Ala., at entrance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ANCHORAGES ANCHORAGE REGULATIONS Anchorage Grounds § 110.194 Mobile Bay, Ala., at entrance. (a) The anchorage grounds. The waters within a radius of 750 yards from a point located 1,000 yards true north from Fort... an anchorage. It may be used for a general anchorage when not required for vessels...

  10. 26 CFR 1.194-2 - Amount of deduction allowable.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... reforestation expenditures made in a taxable year is determined by dividing the amount of reforestation... qualifying reforestation expenditures each year under section 194. However, the maximum amortizable amount is... properties. The limit of $10,000 on amortizable reforestation expenditures applies to expenditures paid or...

  11. 26 CFR 1.194-2 - Amount of deduction allowable.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... reforestation expenditures made in a taxable year is determined by dividing the amount of reforestation... qualifying reforestation expenditures each year under section 194. However, the maximum amortizable amount is... properties. The limit of $10,000 on amortizable reforestation expenditures applies to expenditures paid or...

  12. 49 CFR 194.101 - Operators required to submit plans.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... § 194.119. A pipeline which does not meet the criteria for significant and substantial harm as defined... substantial harm. Operators of substantial harm pipeline facilities must prepare and submit plans to PHMSA for... not operate at a maximum operating pressure established under § 195.406 that corresponds to a stress...

  13. 50 CFR 622.194 - Adjustment of management measures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ATLANTIC Snapper-Grouper Fishery of the South Atlantic Region § 622.194 Adjustment of management measures. In accordance with the framework procedures of the FMP for the Snapper-Grouper Fishery of the South... section for South Atlantic snapper-grouper and wreckfish. (a) Biomass levels, age-structured...

  14. 46 CFR 194.10-5 - Type and location.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-5 Type and location. (a) Integral magazines. (1) Magazines shall be of permanent construction located below the freeboard deck and where practicable below the waterline. (2) Magazines shall not be located in horizontal proximity to...

  15. 46 CFR 194.10-5 - Type and location.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-5 Type and location. (a) Integral magazines. (1) Magazines shall be of permanent construction located below the freeboard deck and where practicable below the waterline. (2) Magazines shall not be located in horizontal proximity to...

  16. 46 CFR 194.10-5 - Type and location.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-5 Type and location. (a) Integral magazines. (1) Magazines shall be of permanent construction located below the freeboard deck and where practicable below the waterline. (2) Magazines shall not be located in horizontal proximity to...

  17. 46 CFR 194.10-5 - Type and location.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-5 Type and location. (a) Integral magazines. (1) Magazines shall be of permanent construction located below the freeboard deck and where practicable below the waterline. (2) Magazines shall not be located in horizontal proximity to...

  18. 46 CFR 194.10-5 - Type and location.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., AND CONTROL OF EXPLOSIVES AND OTHER HAZARDOUS MATERIALS Magazines § 194.10-5 Type and location. (a) Integral magazines. (1) Magazines shall be of permanent construction located below the freeboard deck and where practicable below the waterline. (2) Magazines shall not be located in horizontal proximity to...

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. VizieR Online Data Catalog: Herschel SPIRE/FTS 194-671um survey of GOALS LIRGs (Lu+, 2017)

    NASA Astrophysics Data System (ADS)

    Lu, N.; Zhao, Y.; Diaz-Santos, T.; Xu, C. K.; Gao, Y.; Armus, L.; Isaak, K. G.; Mazzarella, J. M.; van der Werf, P. P.; Appleton, P. N.; Charmandaris, V.; Evans, A. S.; Howell, J.; Iwasawa, K.; Leech, J.; Lord, S.; Petric, A. O.; Privon, G. C.; Sanders, D. B.; Schulz, B.; Surace, J. A.

    2017-06-01

    In this paper we presented a Herschel SPIRE/FTS 194-671um spectroscopic survey of 121 galaxies belonging to a complete, flux-limited sample of 123 luminous infrared galaxies (LIRGs) down to a total IR flux of 6.5x10-13W/m2, selected from the Great Observatories All-Sky LIRG Survey (GOALS; Armus+ 2009PASP..121..559A). All 123 observed targets are listed in Table 1. (3 data files).

  8. Treatment of phimosis with topical steroids in 194 children.

    PubMed

    Ashfield, James E; Nickel, Kyle R; Siemens, D Robert; MacNeily, Andrew E; Nickel, J Curtis

    2003-03-01

    Topical steroids have been advocated as an effective economical alternative to circumcision in boys with phimosis. We evaluated the effectiveness of topical steroid therapy as primary treatment in 194 patients with phimosis. Between January 1996 and November 2000, 228 boys 16 years old or younger were referred for consideration of circumcision. When intervention was determined to be necessary, a 6-week course of topical steroids was used as primary treatment. Efficacy of treatment was evaluated at 3 months from initiation of therapy. Of the 228 patients 15 had such a mild degree of phimosis that no intervention was believed to be necessary, 19 were scheduled directly for circumcision due to cosmetic reasons, parent wishes, or severe phimosis with associated voiding problems and the remaining 194 received topical steroids as primary treatment. Of these 194 patients 25 had coexisting balanitis and 4 had a history of urinary tract infection. Conservative treatment was successful in 87%, 88% and 75% of patients with phimosis alone, coexisting balanitis and history of urinary tract infection, respectively. Overall, circumcision was avoided in 87% of patients treated with topical steroids. Topical steroids are becoming the standard conservative measure for treating phimosis. Our study supports this trend, with an overall efficacy of 87%.

  9. Short-lived isomers in 192Po and 194Po

    NASA Astrophysics Data System (ADS)

    Andel, B.; Andreyev, A. N.; Antalic, S.; Heßberger, F. P.; Ackermann, D.; Hofmann, S.; Huyse, M.; Kalaninová, Z.; Kindler, B.; Kojouharov, I.; Kuusiniemi, P.; Lommel, B.; Nishio, K.; Page, R. D.; Sulignano, B.; Van Duppen, P.

    2016-06-01

    Isomeric states in 194Po and 192Po were studied at the velocity filter SHIP. The isotopes were produced in the fusion-evaporation reactions 141Pr(56Fe, p 2 n )194Po and 144Sm(51V, p 2 n )192Po . Several new γ -ray transitions were attributed to the isomers and γ -γ coincidences for both isomers were studied for the first time. The 459-keV transition earlier, tentatively proposed as de-exciting the isomeric level in 194Po, was replaced by a new 248-keV transition, and the spin of this isomer was reassigned from (11-) to (10-). The de-excitation of the (11-) isomeric level in 192Po by the 154-keV transition was confirmed and a parallel de-excitation by a 733-keV (E 3 ) transition to (8+) level of the ground-state band was suggested. Moreover, side feeding to the (4+) level of the ground-state band was proposed. The paper also discusses strengths of transitions de-exciting 11- isomers in neighboring Po and Pb isotopes.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 46 CFR 194.05-17 - Poisonous articles as chemical stores-Detail requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Poisonous articles as chemical stores-Detail... and Marking § 194.05-17 Poisonous articles as chemical stores—Detail requirements. (a) Poisonous articles as chemical stores and reagents shall be governed by subparts 194.15 and 194.20. (b)...

  15. 46 CFR 194.05-15 - Compressed gases as chemical stores-Detail requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Compressed gases as chemical stores-Detail requirements... and Marking § 194.05-15 Compressed gases as chemical stores—Detail requirements. (a) Compressed gases as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other...

  16. 1 CFR 19.4 - Proclamations calling for the observance of special days or events.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... special days or events. 19.4 Section 19.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL... PROCLAMATIONS § 19.4 Proclamations calling for the observance of special days or events. Except as may be... calling for the observance of special days, or other periods of time, or events, shall be assigned by...

  17. 1 CFR 19.4 - Proclamations calling for the observance of special days or events.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... special days or events. 19.4 Section 19.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL... PROCLAMATIONS § 19.4 Proclamations calling for the observance of special days or events. Except as may be... calling for the observance of special days, or other periods of time, or events, shall be assigned by...

  18. 1 CFR 19.4 - Proclamations calling for the observance of special days or events.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... special days or events. 19.4 Section 19.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL... PROCLAMATIONS § 19.4 Proclamations calling for the observance of special days or events. Except as may be... calling for the observance of special days, or other periods of time, or events, shall be assigned by...

  19. 1 CFR 19.4 - Proclamations calling for the observance of special days or events.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... special days or events. 19.4 Section 19.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL... PROCLAMATIONS § 19.4 Proclamations calling for the observance of special days or events. Except as may be... calling for the observance of special days, or other periods of time, or events, shall be assigned by...

  20. 1 CFR 19.4 - Proclamations calling for the observance of special days or events.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... special days or events. 19.4 Section 19.4 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL... PROCLAMATIONS § 19.4 Proclamations calling for the observance of special days or events. Except as may be... calling for the observance of special days, or other periods of time, or events, shall be assigned by...

  1. 27 CFR 19.4 - Recovery and reuse of denatured spirits in manufacturing processes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Recovery and reuse of denatured spirits in manufacturing processes. 19.4 Section 19.4 Alcohol, Tobacco Products and Firearms... General Provisions § 19.4 Recovery and reuse of denatured spirits in manufacturing processes....

  2. 27 CFR 19.4 - Recovery and reuse of denatured spirits in manufacturing processes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Recovery and reuse of denatured spirits in manufacturing processes. 19.4 Section 19.4 Alcohol, Tobacco Products and Firearms... General Provisions § 19.4 Recovery and reuse of denatured spirits in manufacturing processes....

  3. 27 CFR 19.4 - Recovery and reuse of denatured spirits in manufacturing processes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Recovery and reuse of denatured spirits in manufacturing processes. 19.4 Section 19.4 Alcohol, Tobacco Products and Firearms... General Provisions § 19.4 Recovery and reuse of denatured spirits in manufacturing processes. Certain...

  4. 27 CFR 19.4 - Recovery and reuse of denatured spirits in manufacturing processes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Recovery and reuse of denatured spirits in manufacturing processes. 19.4 Section 19.4 Alcohol, Tobacco Products and Firearms... General Provisions § 19.4 Recovery and reuse of denatured spirits in manufacturing processes. Certain...

  5. 37 CFR 1.94 - Return of models, exhibits or specimens.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Return of models, exhibits or specimens. 1.94 Section 1.94 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL RULES OF PRACTICE IN PATENT CASES National Processing Provisions Models, Exhibits, Specimens § 1.94 Return...

  6. 46 CFR 194.05-13 - Corrosive liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Corrosive liquids as chemical stores-Detail requirements... and Marking § 194.05-13 Corrosive liquids as chemical stores—Detail requirements. (a) Corrosive liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other...

  7. 46 CFR 194.05-19 - Combustible liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Combustible liquids as chemical stores-Detail... and Marking § 194.05-19 Combustible liquids as chemical stores—Detail requirements. (a) Combustible liquid chemical stores and reagents shall be governed by subparts 194.15 and 194.20. (b)...

  8. 46 CFR 194.05-9 - Flammable liquid chemical stores-Detail requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Flammable liquid chemical stores-Detail requirements... and Marking § 194.05-9 Flammable liquid chemical stores—Detail requirements. (a) Flammable liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other flammable liquids...

  9. 46 CFR 194.05-13 - Corrosive liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Corrosive liquids as chemical stores-Detail requirements... and Marking § 194.05-13 Corrosive liquids as chemical stores—Detail requirements. (a) Corrosive liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other...

  10. 46 CFR 194.05-13 - Corrosive liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Corrosive liquids as chemical stores-Detail requirements... and Marking § 194.05-13 Corrosive liquids as chemical stores—Detail requirements. (a) Corrosive liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other...

  11. 46 CFR 194.05-9 - Flammable liquid chemical stores-Detail requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Flammable liquid chemical stores-Detail requirements... and Marking § 194.05-9 Flammable liquid chemical stores—Detail requirements. (a) Flammable liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other flammable liquids...

  12. 46 CFR 194.05-13 - Corrosive liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Corrosive liquids as chemical stores-Detail requirements... and Marking § 194.05-13 Corrosive liquids as chemical stores—Detail requirements. (a) Corrosive liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other...

  13. 46 CFR 194.05-9 - Flammable liquid chemical stores-Detail requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Flammable liquid chemical stores-Detail requirements... and Marking § 194.05-9 Flammable liquid chemical stores—Detail requirements. (a) Flammable liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other flammable liquids...

  14. 46 CFR 194.05-13 - Corrosive liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Corrosive liquids as chemical stores-Detail requirements... and Marking § 194.05-13 Corrosive liquids as chemical stores—Detail requirements. (a) Corrosive liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other...

  15. 46 CFR 194.05-19 - Combustible liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 7 2010-10-01 2010-10-01 false Combustible liquids as chemical stores-Detail... and Marking § 194.05-19 Combustible liquids as chemical stores—Detail requirements. (a) Combustible liquid chemical stores and reagents shall be governed by subparts 194.15 and 194.20. (b)...

  16. 46 CFR 194.05-19 - Combustible liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 7 2011-10-01 2011-10-01 false Combustible liquids as chemical stores-Detail... and Marking § 194.05-19 Combustible liquids as chemical stores—Detail requirements. (a) Combustible liquid chemical stores and reagents shall be governed by subparts 194.15 and 194.20. (b)...

  17. 46 CFR 194.05-9 - Flammable liquid chemical stores-Detail requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 7 2012-10-01 2012-10-01 false Flammable liquid chemical stores-Detail requirements... and Marking § 194.05-9 Flammable liquid chemical stores—Detail requirements. (a) Flammable liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other flammable liquids...

  18. 46 CFR 194.05-19 - Combustible liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 7 2013-10-01 2013-10-01 false Combustible liquids as chemical stores-Detail... and Marking § 194.05-19 Combustible liquids as chemical stores—Detail requirements. (a) Combustible liquid chemical stores and reagents shall be governed by subparts 194.15 and 194.20. (b)...

  19. 46 CFR 194.05-9 - Flammable liquid chemical stores-Detail requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Flammable liquid chemical stores-Detail requirements... and Marking § 194.05-9 Flammable liquid chemical stores—Detail requirements. (a) Flammable liquids as chemical stores and reagents are governed by subparts 194.15 and 194.20. (b) Other flammable liquids...

  20. 46 CFR 194.05-19 - Combustible liquids as chemical stores-Detail requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 7 2014-10-01 2014-10-01 false Combustible liquids as chemical stores-Detail... and Marking § 194.05-19 Combustible liquids as chemical stores—Detail requirements. (a) Combustible liquid chemical stores and reagents shall be governed by subparts 194.15 and 194.20. (b)...

  1. 26 CFR 1.194-4 - Time and manner of making election.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... section, an election to amortize reforestation expenditures under section 194 shall be made by entering... for which reforestation expenditures are being amortized under section 194. The election may only be... election to amortize reforestation expenditures under section 194 may be made by a statement on, or...

  2. 16 CFR 1.94 - Commission proceeding to assess civil penalty.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Commission proceeding to assess civil penalty. 1.94 Section 1.94 Commercial Practices FEDERAL TRADE COMMISSION ORGANIZATION, PROCEDURES AND RULES OF PRACTICE GENERAL PROCEDURES Penalties for Violation of Appliance Labeling Rules § 1.94 Commission proceeding to assess civil penalty. If the...

  3. 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.

  4. [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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Production and decay spectroscopy of 192Po and 194Po

    NASA Astrophysics Data System (ADS)

    Andel, B.

    2015-10-01

    A γ-ray spectroscopy study of the (11-) isomers in 194Po and 192Po was performed at the velocity filter SHIP at GSI (Germany). Nuclei were produced in fusion-evaporation reactions and investigated in the detection set-up at the focal plane after the separator. Several new γ transitions were attributed to the isomers and detailed analysis of the first γ-γ coincidences for both isomers is being prepared. For the reaction 56Fe + 141Pr → 197At*, excitation functions for astatine and polonium isotopes were measured and compared with HIVAP calculations.

  5. Volumes 193, 194, 195 January–December 2013

    PubMed Central

    2013-01-01

    Below is a list of individuals who have reviewed manuscripts for GENETICS during the preparation of volumes 193, 194, and 195 (2013). The aim of GENETICS is to communicate significant research. To succeed, we must recognize what is significant, making sure the presentation is accurate, unambiguous, and easily readable. For this, we depend heavily upon our reviewers, who perform this indispensable service without reward. The quality of the journal strongly reflects the quality of their efforts. We apologize to any reviewer whose name has been inadvertently omitted, and we are sincerely grateful to all.

  6. MiRNA-194 Regulates Palmitic Acid-Induced Toll-Like Receptor 4 Inflammatory Responses in THP-1 Cells.

    PubMed

    Tian, Huiqun; Liu, Chaoqi; Zou, Xiaohua; Wu, Wei; Zhang, Changcheng; Yuan, Ding

    2015-05-13

    There is strong evidence to suggest that inflammatory responses link obesity and diseases, and the understanding of obesity-induced inflammatory mechanisms is central to the pathogenesis of diseases such asnonalcoholic fatty liver disease(NAFLD) and atherosclerosis that are modified by obesity. Based on this, anti-inflammatory treatments become a potential therapies for obesity-related diseases like NAFLD.A critical role of toll-like receptor (TLR) and its downstream molecules such as tumor necrosis factor receptor-associated factor 6(TRAF6) has been documented in inflammatory response induced by fatty acid. TLR pathway regulation provides a new insight to controlling the inflammatory response induced by fatty acid. Taken together, our study was aimed to understand the mechanism of fatty acid-mediated inflammation and look for an effective target which can prevent the inflammatory response induced by obesity. In this study, we used the saturated fatty acid palmitic acid (PA) to activate TLR4 signal pathway in human monocyte cells THP-1 that established an intracellular inflammatory model. Followed with activated TLR4, downstream molecular TRAF6 was upregulated and ultimately induced proinflammatory cytokine production. Based on this model, we also found that PA downregulated miR-194 expression with TLR4 activation. Moreover, our results showed that key signal molecular TRAF6 is a target of miR-194, overexpression of miR-194 directly decreased TRAF6 expression and attenuated the release of proinflammatory cytokine TNF-α in PA-activated monocyte THP-1. We conclude that miR-194 negatively regulates the TLR4 signal pathway which is activated by PA through directly negative TRAF6 expression.

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. New features of superdeformed bands in {sup 194}Hg

    SciTech Connect

    Janssens, R.V.F.; Ahmad, I.; Carpenter, M.P.

    1995-08-01

    A striking difference between superdeformed (SD) nuclei near A = 190 and those in the other regions is the behavior of the dynamic moment of inertia (lm) with the rotational frequency h{omega}. While the (lm) patterns of the SD bands near A = 130 and A = 150 show pronounced variations, the majority of the SD bands near A = 190 display the same large, smooth increase of (lm) within the frequency range 0.15 < {h_bar}{omega} < 0.40 MeV. Current interpretations of this rise of (lm) within mean field theories invoke the gradual alignment of quasiparticles occupying high-N intruder orbitals in the presence of pair correlations. It is a direct consequence of these interpretations that, after the quasiparticle alignments take place, (lm) will exhibit a downturn with increasing {h_bar}{omega} toward the rigid-body value. Up to now, no downturn in (lm) for the SD bands in the A = 190 mass region was observed, raising some doubt as to our understanding of pair correlations and alignment effects at these large deformations. An experiment was carried out at the 88-Inch Cyclotron facility of the Lawrence Berkeley Laboratory where excited states in {sup 194}Hg were populated with the reaction {sup 150}Nd({sup 48}Ca,4n) {sup 194}Hg at a beam energy of 206 MeV. The gamma rays emitted in the reaction were detected with the Gammasphere detector array (32 detectors for this experiment).

  12. Mississippi Canyon 194, Gulf of Mexico: Development case history/geophysical summary

    SciTech Connect

    Kohli, M. )

    1991-03-01

    A 3-D geophysical survey acquired at Cognac (MC 194 field) nine years after the first production shows the effect of reservoir drainage. A redevelopment program currently in progress targeted wells for oil bypassed due to poor sweep efficiency and/or small faults. Revised structural interpretation based on the 3-D showed several additional opportunities in new fault blocks. Attribute measurements were done at all levels where the pay sand was amplitude supported. These data were then tied in great detail with the geology and the production data available for the different reservoirs. Based on the results of the development wells, a good 3-D seismic survey can help locate fluid contacts, detect small faults ({plus minus}50 ft), and reduce dry hole and marginal well risks with better placement of wells.

  13. 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.

  14. 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

  15. Breeding of new rice cultivar 'Tohoku 194' with 'Sasanishiki'-type good eating quality of cooked rice.

    PubMed

    Nagano, Kuniaki; Sasaki, Kunihiko; Endo, Takashi

    2013-06-01

    Cooked rice of 'Sasanishiki' is soft and not as sticky as those of Japanese leading cultivars 'Koshihikari' and 'Hitomebore'. As a method for efficient selection of a breeding line having a good eating quality like that of 'Sasanishiki', the use of physical properties of cooked rice and cooking quality was examined. There were differences of physical properties of the surface layer, starch-iodine blue value per solid substance weight in cooking water and volume expansion of cooked rice between 'Sasanishiki' and 'Hitomebore', these properties being considered to be usable for the selection of breeding lines. Using these traits as selection targets, one line, named 'Tohoku 194', which has eating quality highly similar to that of 'Sasanishiki' and cold tolerance derived from 'Hitomebore', was selected from progeny of a cross between 'Sasanishiki' and 'Hitomebore'. An application for registration as a new variety has been submitted for 'Tohoku 194' under the Japanese Plant Variety Protection Act, and is expected to become a recommended cultivar in Miyagi Prefecture. 'Tohoku 194' may fulfill various demands of consumers and companies in the food industry.

  16. Identification of rice Di19 family reveals OsDi19-4 involved in drought resistance.

    PubMed

    Wang, Lili; Yu, Changchun; Chen, Cong; He, Chunlan; Zhu, Yingguo; Huang, Wenchao

    2014-12-01

    The OsDi19 proteins functioned as transcription factors and played crucial roles in response to abiotic stress. Overexpression of OsDi19-4 in rice increased drought tolerance by enhancing ROS-scavenging activity. Many transcription factors play crucial roles in plant responses to abiotic stress. Here, comprehensive sequence analysis suggested that the drought-induced 19 (Di19) gene family in rice genome contain seven members, and these proteins contained a well-conserved zinc-finger Di19 domain. Most OsDi19 proteins were mainly targeted to the nucleus and have transactivation activity in yeast. Yeast two-hybrid and bimolecular fluorescence complementation assays showed that most OsDi19 proteins could form protein dimers. Expression analysis demonstrated that the OsDi19 genes were differentially and abundantly expressed in vegetative tissues, but expressed little in reproductive tissues and some of the OsDi19 genes were markedly induced by abiotic stresses and hormones in qRT-PCR analysis and microarray data. Overexpression of one stress-responsive gene, OsDi19-4, in rice resulted in significantly increased tolerance to drought stress compared with the wild type plants. Moreover, obviously increased ROS-scavenging ability was detected in the OsDi19-4-overexpressing plants under normal and drought stress conditions. These results suggested that the increased stress tolerance of OsDi19-4-overexpressing plants may be attributable to the enhanced ROS-scavenging activity. Taken together, these studies provide a detailed overview of the rice Di19 gene family, and suggest that the OsDi19 family may play crucial roles in the plant response to abiotic stress.

  17. 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.

  18. Sandwich-like Cu(1.94)S-ZnS-Cu(1.94)S nanoheterostructure: structure, formation mechanism and localized surface plasmon resonance behavior.

    PubMed

    Huang, Feng; Xu, Ju; Chen, Daqin; Wang, Yuansheng

    2012-10-26

    In this communication, a thermolysis route is developed to synthesize novel Cu(1.94)S-ZnS-Cu(1.94)S nanoheterostructures with interesting sandwich-like architectures, taking Cu(1.94)S nanoplates as precursors. Evidently, the trimeric nanostructure is formed by a three-stage process, which includes the Zn-oleate induced assembling of Cu(1.94)S nanoplate couples, the heteronucleation and growth of a ZnS layer between two Cu(1.94)S plates dominated by interfacial diffusion, and the catalyst assisted axial growth of ZnS nanorod following the solution-liquid-solid mechanism. With epitaxial growth of ZnS nanocrystal between two Cu(1.94)S nanoplates, the localized surface plasmon resonance frequency of Cu(1.94)S shifts from 1875 to 1323 nm, indicating that this new material is potentially applicable as a light absorbing agent in laser photothermal therapy. The reported growth mechanism may provide new strategies for designing and fabricating various technologically important polymeric nanoheterostructures.

  19. 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

  20. High-spin level scheme of {sup 194}Pb

    SciTech Connect

    Kutsarova, T.; Stefanova, E. A.; Minkova, A.; Lalkovski, S.; Korichi, A.; Lopez-Martens, A.; Hannachi, F.; Huebel, H.; Goergen, A.; Jansen, A.; Schoenwasser, G.; Khoo, T. L.; Herskind, B.; Bergstroem, M.; Bazzacco, D.; Podolyak, Z.

    2009-01-15

    High-spin states in {sup 194}Pb have been populated in the {sup 168}Er({sup 30}Si,4n) reaction at 142 MeV. The emitted {gamma} rays were detected by the EUROBALL III multidetector array. The level scheme was considerably extended and many previously observed {gamma}-ray transitions were reordered. Four new magnetic rotational bands were observed. The energies and spins of the bandheads of all previously observed magnetic rotational bands were corrected based on the observation of new transitions. From nine observed bands, only one could not be connected to the lower lying states. Based on comparison systematics with neighboring Pb isotopes and tilted-axis cranking model calculations previously reported, configuration assignments to the observed bands have been made.