Heme oxygenase-1 (HO-1), a cytoprotective, pro-angiogenic and anti-inflammatory enzyme, is strongly induced in injured tissues. Our aim was to clarify its role in cutaneous wound healing. In wild type mice, maximal expression of HO-1 in the skin was observed on the 2nd and 3rd days after wounding. Inhibition of HO-1 by tin protoporphyrin-IX resulted in retardation of wound closure. Healing was also delayed in HO-1 deficient mice, where lack of HO-1 could lead to complete suppression of reepithelialization and to formation of extensive skin lesions, accompanied by impaired neovascularization. Experiments performed in transgenic mice bearing HO-1 under control of keratin 14 promoter showed that increased level of HO-1 in keratinocytes is enough to improve the neovascularization and hasten the closure of wounds. Importantly, induction of HO-1 in wounded skin was relatively weak and delayed in diabetic (db/db) mice, in which also angiogenesis and wound closure were impaired. In such animals local delivery of HO-1 transgene using adenoviral vectors accelerated the wound healing and increased the vascularization. In summary, induction of HO-1 is necessary for efficient wound closure and neovascularization. Impaired wound healing in diabetic mice may be associated with delayed HO-1 upregulation and can be improved by HO-1 gene transfer.

Our results suggest a possible role of surgery in limited-stage SCLC. Thus, a randomised study addressing this issue seems to be justified.

No abstract

One-step removal of a dumb-bell tumor by postero-lateral thoracotomy and extended foraminectomy is a safe surgical procedure that can be performed by the thoracic team alone. Early and late surgical results confirm the appropriateness and usefulness of the method.

18189 Background: Bax and Bcl2 proteins are members of Bcl-2 family which plays a critical role in the regulation of apoptosis. There are few data on the occurrence and clinical relevance of these proteins in SCLC. Methods: We have analyzed expression of Bax and Bcl2 in 86 SCLC patients. All patients had limited disease and were treated with surgery followed by chemotherapy between 1982 and 2001 (median follow up 2 years). In all cases the diagnosis of SCLC was established only after the examination of surgical specimen. This series included 59 males and 22 females, 11 T1, 46 T2, 13 T3 and 11 T4 tumors, 41 N0, 15 N1, 24 N2 and 1 N3. Expression of both proteins was evaluated by immunohistochemistry and scored, taking into account proportion of cells with positive staining and staining intensity. H-score was calculated as a proportion of positive cells times staining intensity. Continues data on H-score were used to assess relationships with clinical data. Results: Median H-scores for Bax and Bcl2 were 70 (range 0–300) and 90 (range 0–300) respectively. The positive immunostaining rates (cut-off point of 10%) for Bax and Bcl-2 in the entire group were 81% and 79% respectively. Bax and Bcl-2 expression did not correlate with any clinicopathological parameters such as age, tumor size, lymph node involvement and stage of the disease. Survival was not influenced by expression of Bax (p=0.6) or Bcl2 (p=0.86). There was a significant positive correlation between Bax and Bcl2 expression rates (p=0.018, regression coefficient 0.23). Conclusions: Bax an Bcl2 proteins are commonly overexpressed in SCLC, with tendency for co-expression. Clinical relevance of these markers is questionable in this patient cohort. No significant financial relationships to disclose.