Red Wine Inspired Chromophores as Photodynamic Therapy Sensitizers.

Hydroxypyranoflavylium (HPF) cations are synthetic analogs possessing the same basic chromophore as the pyranoanthocyanins that form during the maturation of red wine. HPF cations absorb strongly in the visible spectral region, and most are fluorescent, triplet-sensitize singlet oxygen formation in solution and are strong photooxidants, properties that are desirable in a sensitizer for photodynamic therapy (PDT). The results of this study demonstrate that several simple HPF dyes can indeed function as PDT sensitizers. Of the eight HPF cations investigated in this work, four were phototoxic to a human cervical adenocarcinoma cell line (HeLa) at the 1-10 µmol dm-3 level, while only one of the eight compounds showed noticeable cytotoxicity in the dark. Neither a Type I nor a Type II mechanism can adequately rationalize the differences in phototoxicity of the compounds. Colocalization experiments with the most phototoxic compound demonstrated the affinity of the dye for both the mitochondria and lysosomes of HeLa cells. The fact that relatively modest structural differences, e.g., the exchange of an electron-donating substituent for an electron-withdrawing substituent, can cause profound differences in the phototoxicity, together with the relatively facile synthesis of substituted HPF cations, makes them interesting candidates for further evaluation as PDT sensitizers.

Bone metastases and skeletal-related events: incidence and prognosis according to histological subtype of lung cancer.

AIM: Estimate the incidence of bone metastases (BM) and skeletal-related events according to the histological subtype of lung cancer and its impact on patient survival. PATIENTS & METHODS: Retrospective cohort study was carried out with patients diagnosed with lung cancer. Cumulative incidence, Kaplan-Meier survival analysis and the risk of death were estimated. RESULTS: In non-small-cell lung cancer (NSCLC), the cumulative incidence of BM during follow-up was 23.8% at 24 months; in small-cell lung cancer, it was 18.5%. The presence of BM in patients with NSCLC was associated with an increased risk of death (hazard ratio: 1.25; 95% CI: 1.04-1.49; p = 0.013). CONCLUSION: This study revealed a high incidence of BM and skeletal-related events. BM was associated with a poor prognosis in NSCLC patients.

The electronic transitions of analogs of red wine pyranoanthocyanin pigments.

There is increasing interest in using natural colorants like anthocyanins in cosmetics, food and pharmaceuticals as replacements for synthetic colorants. During the maturation of red wines, the anthocyanin pigments contained in grapes are transformed via reaction with copigments and metabolic products into pyranoanthocyanins, responsible in part for the final color of the wine. In order to understand structural effects on the absorption spectra of pyranoanthocyanins, the calculated excited state energies and spectroscopic states of a series of substitued pyranoflavylium cation analogs of pyranoanthocyanins have been compared to experimental spectroscopic data for these compounds. The vertical excitation energies, calculated by using the ADC(2) approach, gave excellent agreement with the experimental UV-Vis spectra and the nature of the lowest excited state correlates with the observed photophysical behavior in solution. The present results thus provide a basis for the design of new pyranoflavylium chromophores with the desired colors and photophysics, as well as for understanding the analogous properties of natural pyranoanthocyanin pigments in red wine.

Incidence, associated factors, and survival in metastatic spinal cord compression secondary to lung cancer.

BACKGROUND CONTEXT: Bone metastasis (BM) occurs frequently in patients with lung cancer (LC). The most affected are the bones of the spine, increasing the risk of developing metastatic spinal cord compression (MSCC). Although MSCC is one of the most disabling complications, few studies have reported relevant results related to its frequency and prognosis among patients with LC. PURPOSE: The purpose of this study was to determine the incidence and associated factors of the development of MSCC after BM with LC and its prognosis. STUDY DESIGN/SETTING: This is a cohort study. PATIENT SAMPLE: A cohort of 112 patients with BM because of LC, whose treatment was performed exclusively at the National Cancer Institute, was analyzed. OUTCOME MEASURES: Study outcome measures included incidence of MSCC, factors associated with MSCC, and survival analysis. METHODS: A cohort study was performed involving patients with BM because of LC diagnosed between 2007 and 2011. Clinical and sociodemographic data were extracted from the physical and electronic medical records because of initial diagnosis (up until December 2013). The association between the independent variables and the outcomes was performed by using crude and adjusted odds ratios (ORs), assuming 95% confidence intervals (CIs). For the exploratory evaluation between the independent variables and the time until the outcomes, Kaplan-Meier survival analysis was conducted. To identify if the differences between the curves were statistically significant, a log-tank test was calculated. A Cox multiple regression model, using the forward stepwise method, was applied, aiming to estimate the factors associated with time to death in the different exposure groups. RESULTS: Of the 112 patients with BM, 31 (27.7%) developed MSCC. The univariate analysis showed that patients with three or more involved vertebrae revealed a 6.1 times greater risk of developing MSCC, compared with those with up to two metastatic vertebrae involved (OR: 6.1, 95% CI: 2.5-15.1, p<.001). Among the patients who developed MSCC, the median survival time was 4.4 months (95% CI: 1.5-7.3) and 4.7 months (95% CI: 3.5-5.9) in the patients without MSCC, not being a statistically significant difference (p=.19). After the occurrence of the MSCC, the median survival time was 2.8 months (95% CI: 1.4-4.1). CONCLUSIONS: In this study, a high incidence of MSCC was observed in patients with BM. The study suggests that patients with three or more involved vertebrae per metastasis are more likely to develop MSCC. No alteration in the overall survival time was noticed among the patients with or without MSCC.