Vitamin E offers protection against oxidative stress and is an efficient quencher of singlet oxygen. A recent report suggests that photo-excitation of vitamin E results in the formation of a triplet state (Naqvi et al, Photochem.Photobiol.Sci. 2, 381 (2003)). This leads to the possibility of the triplet state of vitamin E being able to sensitize singlet oxygen and if this is the case it would be counter productive in terms of the biological protective function of vitamin E. We report the production of singlet oxygen, detected by 1270 nm luminescence, from pulsed laser excitation (308 nm) of vitamin E and an analogue, 2,2,5,7,8-pentamethyl-6-hydroxy-chroman (PMHC), with quantum yields between ∼0.1 to 0.2. The luminescence was identified as singlet oxygen from self quenching by vitamin E with solvent-dependent rate constants similar to published values. Whilst the beneficial antioxidant aspects of vitamin E are well established, these results indicate that vitamin E when directly excited can sensitize singlet oxygen formation and may therefore be capable of inducing biochemical and biological damage. The results are discussed in relation to recent reports on the deleterious effects of vitamin E dietary supplementation and pro-oxidant effects of vitamin E.

The development of chemoresistance is a persistent problem during the treatment of cancer. Although reversion or modification of acquired chemoresistance has been previously observed, no systematic exploration has been undertaken. Here, we report a case study of 2 male patients, 62 and 66 years old, both with histologically proven, radiologically progressing, extensively pretreated, metastatic and refractory (≥2 conventional regimens and drug therapy) colorectal adenocarcinoma that was previously treated with FOLFIRI. The patients were resensitized to FOLFIRI after exposure to RRx-001 in the context of a phase-1 study. RRx-001 is a novel, hypomethylating and free-radical-inducing anticancer agent that activates nitrite reduction to NO under hypoxia and has an impact on epigenetic pathways. The repression of DNA methyltransferase 1 by RRx-001 may lead to demethylation and reexpression of silenced tumor suppressor genes, leading to resensitization. These examples provide insight into a nascent strategy to improve the prognosis in heavily pretreated cancer patients and suggest routes for further exploration.

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Both the neurotransmitter serotonin and the unnatural amino acid 5-hydroxytryptophan (5HT), contain the 5-hydroxyindole chromophore. The photochemistry of 5HT is being investigated in relation to the multiphoton excitation of this chromophore to produce a characteristic photoproduct with green fluorescence ('hyperluminescence'). Laser flash photolysis (308 nm) of 5HT in aqueous solution at neutral pH produces both the neutral 5-indoloxyl radical (λ max 400-420 nm) and another transient absorption with λ max 480 nm and lifetime of 2 μs in deaerated solutions. Based on quenching by oxygen and β-carotene, the species at 480 nm is identified as the triplet excited state of 5HT. In acidic solution a new oxygen-insensitive intermediate with λ max 460 is assigned to the radical cation of 5HT. Time-resolved measurements of luminescence at 1270 nm have shown that the triplet state of 5HT is able to react with oxygen to form singlet excited oxygen ( 1 O 2 *) with a quantum yield of ∼0.1. However, 5HT has also been found to be an effective quencher of singlet oxygen with a second order rate constant of 1.3 × 10 8 dm 3 mol -1 s -1 . The results are discussed in the light of recent observations on the multiphoton-excited photochemistry of serotonin.

SummaryThe fluorescence of serotonin on binding with β-cyclodextrin has been studied using both steadystate and time-resolved methods. Steady state fluorescence intensity of serotonin at 340 nm showed ∼ 30% increase in intensity on binding with K a ∼ 60 dm 3 mol −1 and the fluorescence lifetimes showed a corresponding increase. In contrast, the characteristic green fluorescence ('hyperluminescence') of serotonin observed upon multiphoton near-infrared excitation with subpicosecond pulses was resolved into two lifetime components assigned to free and bound serotonin. The results are of interest in relation to selective imaging and detection of serotonin using the unusual hyperluminescence emission and in respect to recent determinations of serotonin by capillary electrophoresis in the presence of cyclodextrin. The results also suggest that hyperluminescence occurs from multiphoton excitation of a single isolated serotonin molecule.

SummaryQuantum dots are of considerable interest as highly detectable labels with broad absorption, narrow spectral emission and good quantum yields. The luminescence emission has a longer decay time than that of the most common fluorophores, leading to facile rejection of much background emission (such as autofluorescence from biological samples) by means of gated detection. Here, it is shown that a new technique, true-colour nanosecond time-gated luminescence imaging, can be used for selective detection of quantum dot luminescence and should prove valuable for multiplexed detection on the basis of both spectral emission profile and luminescence decay time.

Background: Colorectal cancer is the fourth most commonly diagnosed cancer and the second leading cause of cancer death. Liver metastases develop in half of all the colorectal cancer (CRC) cases and cause death in ∼90% of patients. We are evaluating the treatment of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using Yttrium-90 radioactive microspheres for subjects with liver progressive disease following failure of first-line FOLFOX (± bevacizumab). We are presenting our preliminary data for the phase II study evaluating the tumor response rates, PFS, and long-term safety and toxicity to SIRT following FOLFOX (± bevacizumab) prior to FOLFIRI. Methods: Subjects with predominantly hepatic metastatic CRC whose disease progressed on first-line FOLFOX (± bevacizumab) based therapy are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives their SIRT treatment(s) followed by second-line FOLFIRI based therapy 4-6 weeks after the final SIRT treatment. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. Results: To date, 9 metastatic CRC subjects have been treated and 11 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. Four of 8 subjects (50%) achieved PFS at 6 months and average TTP is 6.7 months (0.7-17.3 months). Overall treatment has been well tolerated, but one possible study related SAE of liver failure occurred (Subject 8). The OS endpoint has not been achieved. Conclusions: Historically, second-line FOLFIRI has achieved a 2.5 months median PFS. In 8 subjects with predominant liver metastatic CRC, we have observed 50% PFS at 6 months. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of first-line combination chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3692. doi:1538-7445.AM2012-3692

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