Taken together, these results indicate that polyamines are not only produced by cancer tissues but are also supplied from the intestinal lumen and together appear to influence polyamine levels in the body of cancer patients. 3. Polyamines in the body In vitro experiments

showed that cultured cells take up polyamines from their surroundings [34, 35]. In blood circulation, the majority of polyamines are contained in blood cells, especially in red and white blood cells, and therefore increases in blood polyamine concentration indicate concurrent increases in polyamine levels in blood cells [36]. Similarly, intracellular polyamine concentrations in Luminespib cells of otherwise normal tissues and organs in cancer patients can be increased [37].

One examination showed that spermidine and spermine levels are increased in the normal colon mucosa of cancer patients compared to the normal colon mucosa from patients without cancer [37], although another study was unable to detect these differences [38]. Given that polyamine concentrations are increased in the blood cells of cancer patients and numerous blood cells with increased polyamine concentrations exist in normal tissues, the polyamine concentration in normal tissues of cancer patients with increased blood polyamine levels might also be Carteolol HCl increased. In addition, orally

administered radiolabeled polyamines have been shown to be immediately distributed PF 01367338 to almost all organs and tissues [29, 39, 40]. Polyamine concentrations in the blood vary considerably among healthy individuals such that concentrations are not necessarily higher in cancer patients than in otherwise normal subjects [41, 42] and this wide variation precludes the use of polyamine levels as a tumor marker as well as making detection of differences in polyamine concentrations in normal tissues of cancer patients and normal subjects difficult. The kinesis of polyamines may allow distant tissues and organs to influence polyamine levels of all cells in an organism. 4. Polyamines and cancer spread Patients with increased polyamine levels either in the blood or urine are reported to have more advanced disease and worse prognosis compared to those with low levels, regardless of the type of malignancy [4–9]. Because polyamines are essential for cell growth, the increased capability of polyamine synthesis could reflect enhanced tumor proliferation. Therefore, inhibition of polyamine synthesis and availability by cancer cells could retard cancer cell growth. The efficacy of polyamine depletion is prominent in Alvocidib animal experiments.