Heme oxygenase-1 and its metabolites affect pancreatic tumor growth in vivo.

BACKGROUND: Pancreatic cancer (PaCa) is a fatal human cancer due to its exceptional resistance to all current anticancer therapies. The cytoprotective enzyme heme oxygenase-1 (HO-1) is significantly overexpressed in PaCa and seems to play an important role in cancer resistance to anticancer treatment. The inhibition of HO-1 sensitized PaCa cells to chemo- and radiotherapy in vitro. Therefore, we investigated the effects of HO-1 and its metabolites biliverdin, carbon monoxide and iron on PaCa cells. PaCa cell lines with divergent HO-1 expression patterns were used in a murine orthotopic cancer model. HO-1 expression and activity was regulated by zinc (inhibition) and cobalt (induction) protoporphyrin. Furthermore, the influence of cellular HO-1 levels and its metabolites on effects of standard chemotherapy with gemcitabine was tested in vivo and in vitro. RESULTS: High HO-1 expression in PaCa cell lines was associated with increased chemoresistance in vitro. Chemoresistance to gemcitabine was increased during HO-1 induction in PaCa cells expressing low levels of HO-1. The inhibition of HO-1 activity in pancreatic tumors with high HO-1 boosted chemotherapeutic effects in vivo significantly. Furthermore, biliverdin and iron promoted PaCa resistance to chemotherapy. Consequently, specific iron chelation by desferrioxamine revealed profound anticancerous effects. CONCLUSION: In summary, the inhibition of HO-1 and the chelation of iron in PaCa cells were associated with increased sensitivity and susceptibility of pancreatic tumors to chemotherapy in vivo. The metabolites biliverdin and iron seem to be involved in HO-1-mediated resistance to anticancer treatment. Therefore, HO-1 inhibition or direct interference with its metabolites may evolve new PaCa treatment strategies.

Analysis of burned hand function (early versus delayed treatment).

UNLABELLED: The aim of this study was analyze the results of hand function in adult patients with deep partial thickness hand burns. All patients were treated in Kaunas University of Medicine Hospital in Lithuania during the period 2001-2004. MATERIAL AND METHODS: A total of 79 cases were reviewed prospectively. We divided the studied patients into two groups by the envelope method (A group of early and B of delayed necrectomy and plasty). Two treatment methods--early and delayed surgery--have been analyzed. We present results of analysis of hand function in the periods of 3 and 12 months after the burn injuries of the hands. RESULTS: During the study we ascertain that the deficiency of hand function in group A 3 and 12 months after the injury was lower than that in group B. The deficiencies of hand and arm functions decreased over time. After a period of 12 months the deficiency of hand and arm functions in group A reached 12%, while in group B the deficiencies of hand and arm function reached 23% and 26.5%, respectively. The study revealed that the deficiency of hand function because of wrist and hand burn depended on the age of patient, the area of hand burn, time period from the injury to the arriving to a hospital and time to the operation. The strength of digit pinch and hand grasp was larger in group A. Twelve months after the burn the strength measured in A and B groups was larger than that measured 3 months after the burn. The strength of hand grasp in group A in male patients regenerated up to 76%, in female--61% of norm. In group B the strength of hand grasp in male patients regenerated up to 60.8% and in female--39.36%. CONCLUSIONS: During the perspective analysis it was determined that after periods of 3 and 12 months after the injury the strength pinch and grip was statistically significantly larger in group A. The deficiency of hand function, which indicates the general hand function, was statistically significantly lower in group A.

The epidemiology and treatment of adult patients with hand burns in Kaunas University of Medicine Hospital in 1985, 1995, 2001 and 2002.

This study reviews the epidemiology of adult patients with hand burns admitted to Kaunas University of Medicine Hospital in Lithuania during selected four years (1985, 1995, 2001 and 2002). Two hundred and forty six cases were reviewed retrospectively with 74.4% of males and 25.6% of females among them. Median of age was 40 years (38 males, 45 females). Fire (71.9%) was the most common cause of injury; scalds (15.4%) were the second most common reason. The median of burned total body surface area was 12%. Analyzing the burns, 58.9% of them occurred in urban area (57.1% full-thickness burns), and 41.1% in rural (42.9% full-thickness burns). The study revealed that 17.1% (42) males and 3.7% (9) females were affected by alcohol at the time of injury. Early skin grafting was performed in 29.4% cases (mostly in 2001, 2002), delayed--70.6% (mostly in 1985, 1995) of all skin grafting operations. Early grafting was found to give better results in the length of hospital stay. Overall, the median of hospital stay significantly decreased and was 24 days (35 days in 1985, 19 days in 2002).