The anticancer activity of alpha-tomatine against mammary adenocarcinoma in mice.

AIM: To evaluate the anticancer effect of alpha-tomatine (i.p.) either alone or in combination with doxorubicin (i.v.) in a mouse tumour model. METHODS: We studied the effect of repeated alpha-tomatine (0.1 - 9 mg/kg) and/or doxorubicin (2 mg/kg) on the growth and mitotic activity of the solid Ehrlich tumour in vivo, as well as on the survival of the tumour-bearing mice. RESULTS: Monotherapy with alpha-tomatine had a significant dose-dependent anticancer effect which peaked at 1 mg/kg. This was shown by both slowed tumour growth and reduced tumour cell proliferation. We also provide the first evidence that the combination alpha-tomatine (1 mg/kg) and doxorubicin (2 mg/kg) had a synergistic effect and significantly prolonged the survival of the mice. Neither alpha-tomatine nor doxorubicin influenced the infiltration of tumours with CD3+ lymphocytes; nor were we able to find an in vivo modulation of the key molecules of two regulatory pathways reported in vitro as the principal anti-cancer mechanisms of alpha-tomatine, i.e. iNOS and phosphorylated ERK2. However, alpha-tomatine still led to intracellular DNA inhibition and protein synthesis in Ehrlich tumour cells in a short-term culture ex vivo with IC50 values of 8.7 and 6.6 µM. CONCLUSIONS: The results suggest that ΤΟΜ, especially in combination with doxorubicin, may be a promising agent for the treatment of malignant solid tumours. Despite growing knowledge of the mechanisms of ΤΟΜ action in cancer cells, most aspects remain unclear. Parallel organ toxicity, especially potential liver effects, requires careful attention when performing in vivo studies in the future.

Adrenal venous sampling in primary aldosteronism: a low dilution of adrenal venous blood is crucial for a correct interpretation of the results.

OBJECTIVE: In primary aldosteronism, adrenal venous sampling (AVS) is essential for subtype differentiation as it evaluates aldosterone secretion from both adrenals. Selectivity of adrenal sampling is assessed by the ratio of cortisol concentrations in adrenal venous blood and inferior vena cava blood (C(adrenal)/C(ivc)). Since the criteria for selective adrenal sampling differ among the reported literature, we performed a study to evaluate the influence of different selectivity criteria on AVS results. DESIGN AND METHODS: Reports of AVS were screened retrospectively. All AVS were performed with cosyntrophin infusion. Reports containing samples with C(adrenal)/C(ivc)>or=10 taken from both adrenals and at least one other adrenal sample characterised by C(adrenal)/C(ivc)>or=1.1 were enrolled. For each individual, we chose reference samples that were defined by the highest C(adrenal)/C(ivc) achieved from each adrenal. The significance of the remaining samples with C(adrenal)/C(ivc)>or=1.1 was analysed in regard to their respective reference samples. We assessed the impact of analysed samples on identification of lateralisation of aldosterone secretion that is crucial for decisions concerning adrenalectomy. RESULTS: AVS reports of 87 patients were enrolled. A total of 225 adrenal samples were analysed and divided into five groups according to C(adrenal)/C(ivc):1.1-1.99, 2-2.99, 3-4.99, 5-9.99 and >or=10. By comparing reference with analysed samples, a concordant assessment with respect to lateralisation of aldosterone secretion was observed in 39, 52, 72, 85 and 94% of the respective groups of analysed samples. CONCLUSION: AVS provides consistent information when adrenal samples with high cortisol concentrations are used.

Evaluation of the antineoplastic activity of L-rhamnose in vitro. A comparison with 2-deoxyglucose.

The effect of unsubstituted deoxyhexoses, 2-deoxy-D-glucose (2-DG) and L-fucose, on tumor cells has been reported in several papers throughout the last decades. That of a similar deoxysugar, L-rhamnose, which is synthesized in bacteria and plants but not in animal cells, has until today not been explored. In the present study, we examined the effect of L-rhamnose on DNA and protein synthesis, growth and the potential induction of apoptosis of tumor cells in vitro. Using 2-DG for comparison, we studied the effect of L-rhamnose in concentrations up to 20 (32 resp.) mmol/l on the initial velocity of the incorporation of labeled precursors of DNA and proteins in short term cultures of both mouse Ehrlich ascites tumor (EAT) and human HL-60 cells in vitro, and further, on cell proliferation and apoptosis induction in HL-60 cells. Neither cytotoxic nor cytostatic effects of L-rhamnose were observed with the exception of slightly pronounced inhibition of DNA synthesis in EAT cells. From the lacking inhibition of the protein synthesis it can be considered that L-rhamnose does not interfere with energy metabolism, at least not in a similar manner as 2-DG.