Quality of life in breast cancer patients during chemotherapy and concurrent therapy with a mistletoe extract.

BACKGROUND: The effects of standardized aqueous mistletoe extracts on Health Related Quality of Life (HRQoL) of tumor patients needs further evaluation. METHODS: in this non-interventional, prospective clinical investigation the longitudinal course of Quality of Life of 270 breast cancer patients during adjuvant chemotherapy and mistletoe therapy with abnobaVISCUM(®) Mali was investigated. HRQoL was measured 4 times by self-assessment with the QLQ-C30 and QLQ-BR23 questionnaire of the European Organization for Research and Treatment of Cancer (EORTC): at the beginning of mistletoe- and chemotherapy, 4 weeks later, at the end of the chemotherapy and 4 weeks after finishing chemotherapy. Secondary objectives were the tolerability and safety of mistletoe therapy in combination with chemotherapy under conditions of daily practice. RESULTS: after an initial deterioration the average range of all obtained QLQ-C30 function scales (n=262, 48.9-71.5) remained stable even at the last chemotherapy cycle and improved significantly (p<0.0001) to 66.9-80.7 4 weeks later, compared to the initial visit. Also the QLQ-BR23 function scales significantly improved (p<0.0001) 4 weeks later. The symptom scales of the QLQ-C30 remained stable under chemotherapy even at the final chemotherapy cycle and decreased from 16.2 to 44.1 at the initial visit to 11.2-29.9 (p<0.001) at the final visit. These results were comparable to the subgroup with initial visit before chemotherapy (n=114) in which rather stable function scales during chemotherapy (difference of the mean values: 9.6 to -3.7) and only little increase of symptoms (difference: 13.2 to -4.9) was measured. The tolerability of the therapy was judged by the physicians as good or very good for 91% of the patients and the efficacy was rated as good or very good for 94%. 89% of the patients reported about a good or very good benefit. CONCLUSION: the overall results point to a relevant stabilisation of Health Related Quality of Life during various chemotherapy regimes, possibly due to a reduction of chemotherapy caused side effects with an excellent tolerability of the mistletoe therapy.

Unexpected effects of a heterozygous dnmt1 null mutation on age-dependent DNA hypomethylation and autoimmunity.

DNA methylation modifies gene expression. Methylation patterns are established during ontogeny, but they change with aging, usually with a net decrease in methylation. The significance of this change in T cells is unknown, but it could contribute to autoimmunity, senescence, or both. We examined the effects of a null mutation in DNA methyltransferase 1 (Dnmt1), a gene maintaining DNA methylation patterns, on immune aging. Whereas aged control mice developed hypomethylated DNA, autoimmunity, and signs of immune senescence as predicted, the knockout mice surprisingly increased DNA methylation and developed signs of autoimmunity and senescence more slowly. To identify potential mechanisms, we compared transcripts of DNA methyltransferase and methylcytosine binding protein family members in control and knockout mice. MeCP2, a methylcytosine binding protein involved in gene suppression and chromatin inactivation, was the only transcript differentially expressed between old knockout mice and controls, and thus it is a candidate for a gene product mediating these effects.

Effects of somatostatin on luminal transit and absorption of nutrients in the proximal gut of minipigs.

A discrepancy exists on the effects of somatostatin on the absorption of nutrients: in humans, absorption was found to be reduced, whereas in rats no effects were observed. However, intestinal absorption might be influenced by the transit rate of contents. This was not considered in previous studies. Therefore, we investigated simultaneously the effects of somatostatin on the absorption of nutrients and on luminal transit. In five minipigs (44-62 kg), a 150-cm segment of the proximal jejunum was temporarily isolated by two cannulas and perfused with an oligomer diet (60% carbohydrate, 18% protein, and 22% fat). The perfusion rate was 2 kcal/min. Flow rate and mean transit time were determined by markers (Cr-EDTA and Cu-EDTA). Somatostatin was infused intravenously at rates of 0.5, 1.25, 2.5, and 5 micrograms/kg/hr. In control experiments saline was administered intravenously. Somatostatin dose-dependently diminished flow rate of luminal contents and increased the transit time. At the largest dose of somatostatin (5 micrograms/kg/hr) flow rate was reduced by 50% compared with control infusion of saline (1.0 +/- 0.4 vs 2.0 +/- 0.05 ml/min, P < 0.05), and transit time was increased 3.6-fold (39.8 +/- 4.7 vs 11.2 +/- 4.9 min; P < 0.05). Somatostatin also dose-dependently enhanced the absorption of nutrients and energy. However, the increase in absorption was small compared with the effects on flow rate and transit time. At the largest dose (5 micrograms/kg/hr) absorption of energy, carbohydrate, protein, and fat was enhanced only by 9.7%, 7.0%, 5.2%, and 15.3%, respectively (49.9 vs 40.2%, 50.9 vs 43.9%, 67.3 vs 62.1%, and 30.1 vs 14.8% during saline infusion; P < 0.05). Results indicate that the major effects of somatostatin consist in a marked reduction of flow rate and a delay of luminal transit. The small increase in absorption was caused by the delay in transit and the prolonged contact of the nutrients with the mucosa. Therefore, in absorption studies, effects on transit need to be considered.