Peginterferon Beta-1a Shows Antitumor Activity as a Single Agent and Enhances Efficacy of Standard of Care Cancer Therapeutics in Human Melanoma, Breast, Renal, and Colon Xenograft Models.

Because of its tumor-suppressive effect, interferon-based therapy has been used for the treatment of melanoma. However, limited data are available regarding the antitumor effects of pegylated interferons, either alone or in combination with approved anticancer drugs. We report that treatment of human WM-266-4 melanoma cells with peginterferon beta-1a induced apoptotic markers. Additionally, peginterferon beta-1a significantly inhibited the growth of human SK-MEL-1, A-375, and WM-266-4 melanoma xenografts established in immunocompromised mice. Peginterferon beta-1a regressed large, established WM-266-4 xenografts in nude mice. Treatment of SK-MEL-1 tumor-bearing mice with a combination of peginterferon beta-1a and the MEK inhibitor PD325901 ((R)-N-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodophenylamino)benzamide) significantly improved tumor growth inhibition compared with either agent alone. Examination of the antitumor activity of peginterferon beta-1a in combination with approved anticancer drugs in breast and renal carcinomas revealed improved antitumor activity in these preclinical xenograft models, as did the combination of peginterferon beta-1a and bevacizumab in a colon carcinoma xenograft model.

B(2)A(')-X(2)A(') detection of vibrationally excited HCO produced by the O((3)P)+C(2)H(4) reaction.

The distribution of rotational and vibrational energy in HCO produced by the O((3)P)+C(2)H(4) reaction has been measured using laser-induced fluorescence detection via the B(2)A(')-X(2)A(') transition. Over a detection wavelength range of 248-290 nm, our experiments have shown that HCO is formed in both the ground state and in at least six vibrationally excited states with up to two quanta of energy in the C-O stretch and the bending mode. Dispersed fluorescence experiments were conducted to positively assign all of the HCO vibrational bands. The experiments confirmed that many bands, including the B(000)-X(000) band, are affected by overlap with other HCO bands. Spectral modeling was used to separate the contributions of overlapping HCO B-X bands and to determine a nascent HCO rotational temperature of approximately 600 K, corresponding to approximately 6% of the total energy from the O((3)P)+C(2)H(4) reaction. HCO vibrational distributions were determined for two different average collision energies and were fit with vibrational temperatures of 1850+/-80 K and 2000+/-100 K, corresponding to approximately 15% of the total energy. The observed Boltzmann distribution of vibrational energy in HCO indicates that HCO and CH(3) are formed by the dissociation of an energized intermediate complex.