Approximately 30% of lung cancer patients will develop central airway obstruction (CAO). Interventional therapeutic bronchoscopy including airway stenting (AS) providing immediate and effective palliation is therefore essential to improve quality of life (QoL). However, no report has demonstrated the survival benefit of AS. We retrospectively reviewed 65 patients with CAO due to lung cancer who underwent AS from June 1994 to May 2008. Seventy-nine stents were required. Silicon, metallic, or both stents were placed in 42 (60%), 19 (29%), or eight (11%) patients, respectively. Single stent was required in 53 (83%) patients, double in 10 (14%), and triple in two (3%). AS could provide acute relief of central airway and significant improvement was seen in 98% of patients. Fifty-nine patients with detailed observations were assessed further. Morbidity and mortality rates were 22% and 8%, respectively. AS resulted in 25.2% of one-year survival rate and 6.2 months of median survival time (MST). AS followed by adjuvant therapy provided a four-month increase in MST, although overall survival was not significantly changed. This study represents a single-institution experience. Although an aggressive strategy of AS is justified in order to improve symptoms and QoL, AS itself did not contribute to survival benefit.
Abstract. ATX-s10 is a novel and second-generation photosensitizer for photodynamic therapy (PDT). In order to conduct clinical trials of ATX-s10-PDT and/or extend its clinical applications, it is very important to elucidate the mechanisms of the action of ATX-s10-PDT. We examined the apoptic response against ATX-s10-PDT using a Bcl-2 or Bcl-2 mutant overexpressing cells. Using fluorescent microscopy, ATX-s10 localized not only to mitochondria but also to lysosomes and possibly other intracellular organelles, but not to the plasma membrane or the nucleus. These results suggest that ATXs10-PDT can damage mitochondria and lysosomes. By Western blot analysis, ATX-s10-PDT damaged Bcl-2, which localized preferentially at mitochondrial membranes, and caused Bcl-2 to cross-link immediately after laser irradiation. However, ATX-s10-PDT was not able to rapidly induce morphologically typical apoptosis (i.e. chromatin condensation and fragmentation) as PDT using mitochondria targeted photosensitizers, such as phthalocyanine 4 (Pc 4). Pharmacological inhibitions of lysosomal cytokine protease cathepsins, such as cathepsin B and D, protected MCF-7c3 cells (human breast cancer cells expressing stably transfected procaspase-3) from apoptosis caused by ATX-s10-PDT. Overexpression of wildtype Bcl-2 or Bcl-2Δ33-54 resulted in relative resistance of cells to ATX-s10-PDT, as assessed by the degree of morphological apoptosis or loss of clonogenicity. We conclude that lysosomal damage by ATX-s10-PDT can initiate apoptotic response and this apoptotic pathway can be regulated by photodamage to Bcl-2 via mitochondrial damage.
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