Combretastatins: In vitro structure-activity relationship, mode of action and current clinical status.

For the first time combretastatins were isolated from African willow tree Combretum Caffrum. Subsequent studies have shown the impact of combretastatin A4 phosphate, a water-soluble prodrug, on endothelial cells in tumor vascular system. The same effect was not observed in the vascular system. This selectivity is associated with combretastatins mechanism of action: binding to colchicine domain of microtubules, which affects the cytoskeleton functionality of immature endothelial cells. At the same time, combretastatins directly induce cell death via apoptosis and/or mitotic catastrophe pathways. The combination of both elements makes combretastatin an anticancer compound of high efficiency. The cis-configuration is crucial for its biological activity. To date, many derivatives were synthesized. The attempts to resolve spontaneous isomerization to less active trans-stilbene derivative are still in progress. This issue seems to be overcome by incorporation of the ethene bridge with heterocyclic moiety in combretastatins structure. This modification retains the cis-configuration and prevents isomerization. Nevertheless, combretastatin A4 phosphate disodium is still the most potent compound of this group. The combination therapy, which is the most effective treatment, includes combretastatin A4 phosphate (CA4P) and conventional chemotherapeutics and/or radiotherapy. CA4P is relatively well tolerated giving adverse events of moderate severity, which includes: nausea, vomiting, headache, and tumor pain. The aforementioned effects subside on the day of drug administration or on the following day.

Back pain in lower and upper secondary school pupils living in urban areas of Poland. The case of Poznan.

BACKGROUND: To determine the lifetime prevalence and characteristics of non-specific back pain (low back pain, upper back pain) and neck pain in adolescents living in urban areas of Poland. We also studied the impact of back/neck pain on adolescents' daily activity as well as the association of back pain with computer use, watching TV, physical work, and physical activity. MATERIAL AND METHODS. A school-based questionnaire survey of back pain and physical activity, computer use, watching TV and functional disorders was distributed among 1475 randomly selected adolescents aged 13 to 20 years attending lower and upper secondary schools in Poznan, Poland. RESULTS: A total of 986 (67%) teenagers reported having experienced one or more episodes of back/neck pain in their lives. Low back pain was the most common presentation. Back/neck pain symptoms appeared mostly between the 14th and 16th year of life. The daily activities mostly impaired by back/neck pain were physical activity, learning/concentration and lifting objects. No significant differences were found in computer use and physical activity between adolescents with and without a history of back/neck pain. Pain-free teenagers watched TV significantly longer. Boys with back/neck pain performed physical work more frequently than pain-free boys. CONCLUSIONS: 1. Compared to adolescents and adults in other European countries, the lifetime prevalence of back/neck pain in Polish adolescents living in urban areas is similar. 2. The findings support the hypothesis that physical activity, computer use and watching TV cannot be regarded as risk factors for back/neck pain. 3. Back/neck pain may have a negative influence on the daily activities of adolescents. Nevertheless, this impact is probably temporary and adolescents seem to develop strategies for coping with pain in order to participate normally in daily activities. More detailed studies of these coping strategies are recommended.