Dobutamine-atropine stress echocardiography and clinical data for predicting late cardiac events in patients with suspected coronary artery disease

purpose: To compare the relative value of clinical variables with dobutamine-atropine stress echocardiography to predict cardiac events during long-term follow-up. Dobutamine stress echocardiography is increasingly used for the detection of coronary artery disease, but little is known of its prognostic value. patients and methods: A total of 430 patients (310 men; mean age 61 years, range 22 to 90) were enrolled in the study. Patients were referred for chest pain complaints and were unable to perform an adequate exercise stress test. All patients underwent dobutamine-atropine stress test (incremental dobutamine infusion: 10 to 40 μ/kg/minute, continued with atropine 0.25 to 1 mg intravenously if necessary to achieve 85% of the age predicted maximal heart rate, without symptoms or signs of ischemia) and clinical cardiac evaluation. Follow-up was 17 ± 5 months, with a minimum of 6 months; 3 patients were lost to follow-up. Cardiac events were defined as cardiac death, nonfatal myocardial infarc

Tumor cell survival pathways activated by photodynamic therapy: a molecular basis for pharmacological inhibition strategies

Photodynamic therapy (PDT) has emerged as a promising alternative to conventional cancer therapies such as surgery, chemotherapy, and radiotherapy. PDT comprises the administration of a photosensitizer, its accumulation in tumor tissue, and subsequent irradiation of the photosensitizer-loaded tumor, leading to the localized photoproduction of reactive oxygen species (ROS). The resulting oxidative damage ultimately culminates in tumor cell death, vascular shutdown, induction of an antitumor immune response, and the consequent destruction of the tumor. However, the ROS produced by PDT also triggers a stress response that, as part of a cell survival mechanism, helps cancer cells to cope with the PDT-induced oxidative stress and cell damage. These survival pathways are mediated by the transcription factors activator protein 1 (AP-1), nuclear factor E2-related factor 2 (NRF2), hypoxia-inducible factor 1 (HIF-1), nuclear factor κB (NF-κB), and those that mediate the proteotoxic stress response. The survival pathways are believed to render some types of cancer recalcitrant to PDT and alter the tumor microenvironment in favor of tumor survival. In this review, the molecular mechanisms are elucidated that occur post-PDT to mediate cancer cell survival, on the basis of which pharmacological interventions are proposed. Specifically, pharmaceutical inhibitors of the molecular regulators of each survival pathway are addressed. The ultimate aim is to facilitate the development of adjuvant intervention strategies to improve PDT efficacy in recalcitrant solid tumors