Jean F. Vollano
Johnson Matthey
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Featured researches published by Jean F. Vollano.
Archive | 1991
Christen M. Giandomenico; Michael J. Abrams; Barry A. Murrer; Jean F. Vollano; Christopher F. J. Barnard; Kenneth R. Harrap; Phyllis M. Goddard; Lloyd R. Kelland; Sarah E. Morgan
The advent of cisplatin was a breakthrough in the chemotherapy of certain cancers. Its success, in spite of adverse effects such as nephrotoxicity, nausea and vomiting, ototoxicity and myelosuppression, attests to its efficacy1. Still, the cost of treatment, in terms of patient quality of life, underscores the need for an efficacious drug with milder side effects. Carboplatin is an example of an agent specifically developed to reduce side effects while retaining the antitumor activity of cisplatin2. Its tremendous success, following its introduction in Europe and the US, attests to the importance of addressing patient quality of life. Although, oral chemotherapeutic agents are not presently a significant factor in cancer treatment, a properly designed agent could offer significant advantages in terms of a patients’ comfort and convenience, and anticipates the possibility of outpatient chemotherapy. At Johnson Matthey, in conjunction with the Institute of Cancer Research and Bristol-Myers Squibb, a portion of our platinum antitumor drug discovery program is devoted to the design and development of an orally active platinum antitumor drug. This paper describes the synthesis, reactions, and a few of the biological properties of a new class of antitumor agents that possess many characteristics required of an orally active antitumor agent.
International Journal of Radiation Oncology Biology Physics | 1989
Julia A. O'Hara; Evan B. Douple; Michael J. Abrams; Donald J. Picker; Christen M. Giandomenico; Jean F. Vollano
The effects of the combination of several meso-substituted, water soluble metalloporphyrins with ionizing radiation on hypoxic and oxic monolayers of Chinese hamster fibroblast (V79N) cells were studied. The metalloporphyrins tested included a series of cationic metalloporphyrins complexed with Co(III), Zn(II), Fe(III), Cu(II), Pd(II) or Mn(III) and a series of anionic porphyrins chelated with Co(III), Fe(III), Cu(II), Rh(III), Mn(III) or Sn(IV). Both cationic and anionic free porphyrins were also tested. Cationic ligands were tetrakis(4N-methylpyridyl)porphine [TMPyP], tetrakis(4N-trimethylamino phenyl)porphine [TMAP], tetrakis(4N-butylpyridyl)porphine [TBPyP] and tetrakis(3N-methylpyridyl)porphine [3TMPyP]. Anionic ligands tested were tetrakis(4-sulfonato phenyl)porphine [TPPS], tetrakis(biphenyl)porphine sulfonate [TBPS] and tetrakis(4-carboxyphenyl)porphine [TCPP]. SER calculated from survival curves and SFR from one radiation dose were used to assess the relative effectiveness of this class as non-cytotoxic hypoxic and oxic cell-kill potentiators. Comparisons were made at 100 microM, which was essentially non-toxic (greater than 70% survival) for all porphyrins tested except for Co[TMPyP] (approximately 50% survival after 1 hour at 37 degrees C under oxic conditions). The greatest effects on radiation-induced cell kill were achieved with Co[TPPS] and Co[TMPyP] with SER values of 2.3 and 2.4 respectively. Porphyrin analogs with no coordinated metal were found to be less active than the same compound with metal. The overall charge on the molecule did not systematically relate to the biological activity of the compounds tested.
Radiation Research | 1987
Beverly A. Teicher; John L. Jacobs; Kathleen N. S. Cathcart; Michael J. Abrams; Jean F. Vollano; Donald H. Picker
The radiosensitizing potential in hypoxic EMT6 cells of several complexes of Co(III) and Fe(III) has been examined. The cytotoxicity of each of the agents toward oxygenated and hypoxic EMT6 cells was tested over the concentration range of 1 to 500 micron for 1-h drug exposure. There was no statistically significant difference between the cytotoxicity of these complexes toward oxygenated and hypoxic cells. Based on these findings, 100 micron was selected as the drug concentration for the initial assessment of radiosensitizing potential. The radiation survival of EMT6 cells in the presence of 100 microM drug for a series of Co(III) complexes in which the number of nitro ligands was varied showed that the hexanitro and the triamine-trinitro complexes are very effective radiosensitizers. The trans-tetrammine dinitro complex was a more effective radiosensitizer than the corresponding cis-dinitro complex. The diethylenetriamine and 1,10-phenanthroline complexes were very effective radiosensitizers, producing dose-modifying factors of 2.4. The trans-tetrammine dichloro complex was moderately effective, giving a dose-modifying factor of 1.9. On the other hand, the hexammine and triammine tricyano complexes and the trans-dinitro complex with negatively charged acetylacetonate ligands were ineffective as radiosensitizers in this system. Finally, three complexes with cyclopentadienyl ligands were examined. The ferricenium salt itself was a moderately effective radiosensitizer, giving a dose-modifying factor of 2.0. However, both the dimethylferricenium salt and the analogous cobalt complex were ineffective. The FSaIIC fibrosarcoma was used to study radiosensitizing potential in vivo. The trans-tetramminedinitro complex was administered at doses of 100, 200, or 300 mg/kg as a single ip injection 1 h prior to irradiation or as three daily ip injections. There was increasing dose modification with increasing drug dosage. With a fractionated radiation protocol in which five daily fractions of 2, 3, or 4 Gy were administered to the tumor-bearing limb with ip drug injections of 100 or 200 mg/kg given 1 h prior to irradiation, a dose-modifying effect of 1.6 was observed with 5 X 200 mg/kg of the drug.
Journal of Photochemistry and Photobiology B-biology | 1997
Jean F. Vollano; Gerald E. Bossard; S.A. Martellucci; M.C. Darkes; Michael J. Abrams; Robert C. Brooks
Abstract A simple synthetic route to a ruthenium(II)-2,3-naphthalocyanine-bis-benzonitrile complex is presented. A series of ligands can be substituted in the axial position of this complex, which confers water solubility on the ruthenium(II)-2,3-naphthalocyanines (Ru(II) -2,3-Ncs). The ability of these complexes to function as potential sensitizers for photodynamic therapy was investigated. The sensitizers presented in this paper have Q-band absorption maxima in the 710–760 nm range, with extinction coefficients around 1 × 10 5 M −1 cm −1 . The activity of these complexes was tested in vitro against the HeLa cell line and was found to be in the micromolar range. The photobleaching of the complexes was also studied.
Inorganica Chimica Acta | 1989
Jean F. Vollano; Donald H. Picker; John Statler
Abstract Several amine gold complexes of 1,2-bis(diphenylphosphino)ethane (dppe) and triphenylphosphine (PPh 3 ), having the general formulae [(AuNH 2 R) 2 (dppe)](NO 3 ) 2 and [Au(NH 2 R)(PPh 3 )]NO 3 (R=alkyl, hydrogen), have been prepared by the addition of an amine to (AuNO 3 ) 2 (dppe) or Au(NO 3 )(PPh 3 ). These gold(I) amine arylphosphine complexes represent a new class of coordination compounds. The complexes are dicationic in a chloroform/methanol solution used for 31 P NMR spectroscopy. The dppe series displays a small downfield chemical shift as more hindered amines are coordinated. A similar range of chemical shifts was observed for two analogous triphenylphosphine complexes.
Archive | 1989
Michael J. Abrams; Christen M. Giandomenico; Barry A. Murrer; Jean F. Vollano
Inorganica Chimica Acta | 1987
Michael J. Abrams; Christen M. Giandomenico; Jean F. Vollano; David Aaron Schwartz
Archive | 1991
Michael J. Abrams; Christen M. Giandomenico; Barry A. Murrer; Jean F. Vollano
Archive | 1995
Michael J. Abrams; Gerald E. Bossard; Robert C. Brooks; Geoffrey W. Henson; Jean F. Vollano
Archive | 1992
Michael J. Abrams; Robert C. Brooks; Gerald E. Bossard; Jean F. Vollano