Photodynamic therapy (PDT) is a treatment modality that utilizes a photosensitizing drug activated by laser generated light, and is proving effective for oncologic and nononcologic applications. This report provides an overview of photosensitizers, photochemistry, photobiology, and the lasers involved in photodynamic therapy. Clinical and preclinical PDT studies involving Photofrin and various second generation photosensitizers are reviewed.

Photodynamic therapy (PDT) elicits both apoptotic and necrotic responses within treated tumors and produces microvascular injury leading to inflammation and hypoxia. PDT also induces expression of angiogenic and survival molecules including vascular endothelial growth factor, cyclooxygenase-2 (COX-2), and matrix metalloproteinases. Adjunctive administration of inhibitors to these molecules improves PDT responsiveness. In the current study, we examined how the combination of PDT and COX-2 inhibitors improve treatment responsiveness. Photofrin-mediated PDT combined with either celecoxib or NS-398 increased cytotoxicity and apoptosis in mouse BA mammary carcinoma cells. Immunoblot analysis of protein extracts from PDT-treated cells also showed poly(ADP-ribose) polymerase cleavage and Bcl-2 degradation, which were further enhanced following combined therapy. Tumor-bearing mice treated with PDT and either celecoxib or NS-398 exhibited significant improvement in long-term tumor-free survival when compared with PDT or COX-2 inhibitor treatments alone. The combined procedures did not increase in vivo tumor-associated apoptosis. Administration of celecoxib or NS-398 attenuated tissue levels of prostaglandin E 2 and vascular endothelial growth factor induced by PDT in treated tumors and also decreased the expression of proinflammatory mediators interleukin-1B and tumor necrosis factor-A. Increased tumor levels of the antiinflammatory cytokine, interleukin 10, were also observed following combined treatment. This study documents for the first time that adjunctive use of celecoxib enhances PDTmediated tumoricidal action in an in vivo tumor model. Our results also show that administration of COX-2 inhibitors enhance in vitro photosensitization by increasing apoptosis and improve in vivo PDT responsiveness by decreasing expression of angiogenic and inflammatory molecules. (Cancer Res 2005; 65(20): 9473-8)

; two Li + ISEs as reference electrodes; three solid crystal pellet ISEs for Cl À , Br À , and I À ; an iridium oxide electrode for pH; a carbon ring electrode for conductivity; a Pt electrode for oxidation reduction potential (Eh); a Pt and two Ag electrodes for determination of Cl À , Br À , and I À using chronopotentiometry (CP); a Au electrode for identifying redox couples using cyclic voltammetry (CV); and a Au microelectrode array that could be used for either CV or to indicate the presence of several heavy metals, including Cu 2+ , Cd 2+ , Pb 2+ , Fe 2/3+ , and Hg 2+ using anodic stripping voltammetry (ASV). The WCL sensors and analytical procedures have been calibrated and characterized using standard solutions, geological Earth samples, Mars simulants, and cuttings from a Martian meteorite. Sensor characteristics such as limits of detection, interferences, and implications of the Martian environment are also being studied. A sensor response library is being developed to aid in the interpretation of the data.

We analyze and compare different aspects of InAs/InAsSb and InAs/GaSb type-II superlattices for infrared detector applications and argue that the former is the most effective when implemented for mid-wavelength infrared detectors. We then report results on an InAs/InAsSb superlattice based mid-wavelength high operating temperature barrier infrared detector. At 150 K, the 50% cutoff wavelength is 5.37 μm, the quantum efficiency at 4.5 μm is ∼52% without anti-reflection coating, the dark current density under −0.2 V bias is 4.5 × 10−5 A/cm2, and the dark-current-limited and the f/2 black-body (300 K background in 3–5 μm band) specific detectivities are 4.6 × 1011 and 3.0 × 1011 cm-Hz1/2/W, respectively. A focal plane array made from the same material exhibits a mean noise equivalent differential temperature of 18.7 mK at 160 K operating temperature with an f/2 optics and a 300 K background, demonstrating significantly higher operating temperature than InSb.

A new ambipolar molecule based on a carbazole−fluorene−oxadiazole triad is reported. In a single-active-layer device, the compound reveals a deep-blue electroluminescence with CIE coordinates of (0, 157, 0.079). An external quantum efficiency of 4.7% is achieved if the ambipolar material is formed into a thin layer by thermal evaporation.

Background A conditionally replication-defective human cytomegalovirus (CMV) vaccine (V160) derived from AD169 and genetically engineered to express CMV pentameric complex (gH/gL/pUL128/pUL130/pUL131) was developed and evaluated for phase 1 vaccine safety and immunogenicity in CMV-seronegative and CMV-seropositive adults. Methods Subjects received 3 doses of V160 or placebo on day 1, month 1, and month 6. Four vaccine dose levels, formulated with or without aluminum phosphate adjuvant, were evaluated. Injection-site and systemic adverse events (AEs) and vaccine viral shedding were monitored. CMV-specific cellular and humoral responses were measured by interferon-gamma ELISPOT and virus neutralization assay up to 12 months after last dose. Results V160 was generally well-tolerated, with no serious AEs observed. Transient, mild-to-moderate injection-site and systemic AEs were reported more frequently in vaccinated subjects than placebo. Vaccine viral shedding was not detected in any subject, confirming the nonreplicating feature of V160. Robust neutralizing antibody titers were elicited and maintained through 12 months postvaccination. Cellular responses to structural and nonstructural viral proteins were observed, indicating de novo expression of viral genes postvaccination. Conclusions V160 displayed an acceptable safety profile. Levels of neutralizing antibodies and T-cell responses in CMV-seronegative subjects were within ranges observed following natural CMV infection. Clinical Trial Registration . NCT01986010.

Ertapenem is a parenteral beta-lactam carbapenem antibiotic. This open-label study examined the pharmacokinetics of single 1-g intravenous doses of ertapenem, administered over 30 minutes, in patients with mild, moderate, and advanced renal insufficiency (RI) and in patients with end-stage renal disease (ESRD) requiring hemodialysis. Pharmacokinetics were compared with historical controls pooled across healthy young and elderly subjects. Area under the concentration-time curve from time zero to infinity increased 7% in mild, 53% in moderate, 158% in advanced RI, and 192% in ESRD; end of infusion concentration changed minimally; half-life was 4.5 hours in the historical control group and 4.4, 6.1, 10.6, and 14.1 hours in mild RI, moderate RI, advanced RI, and ESRD, respectively. Hemodialysis cleared approximately 30% of the dose. The recommended dose in mild to moderate RI and after hemodialysis is unchanged at 1 g daily; and in advanced RI and ESRD is reduced to 0.5 g daily. If the daily dose is given 6 hours prior to hemodialysis, a supplementary 150-mg dose (30% of the daily dose) is recommended postdialysis.

Loss of p53 function has been correlated with decreased sensitivity to chemotherapy and radiation therapy in a variety of human tumors. Comparable analysis of p53 status with sensitivity to oxidative stress induced by photodynamic therapy has not been reported. In the current study we examined photosensitivity in human promyelocytic leukemia HL60 cells exhibiting either wild-type p53, mutated p53 or deleted p53 expression. Experiments were performed using a purpurin, tin ethyl etiopurpurin (SnET2)-, or a porphyrin, Photofrin (PH)-based photosensitizer. Total SnET2 accumulation was comparable in all three cell lines. Uptake of PH was highest in cells expressing wild-type p53 but incubation conditions could be adjusted to achieve equivalent cellular PH levels during experiments that analyzed photosensitivity. Survival measurements demonstrated that HL60 cells expressing wild-type p53 were more sensitive to PH- and SnET2-mediated photosensitization, as well as to UVC irradiation, when compared to HL60 cells exhibiting deleted or mutated p53 phenotypes. A rapid apoptotic response was observed following purpurin- and porphyrin-induced photosensitization in all cell lines. Results of this study indicate that photosensitivity is increased in HL60 cells expressing wild-type p53 and that photosensitizer-mediated oxidative stress can induce apoptosis through a p53-independent mechanism in HL60 cells.