ABSTRACT
Background and aims: Although many cancer patients suffer from malnutrition or cancer cachexia, there is no standard of care so far due to limited intervention trials. Pooled data from two combined trials were analyzed regarding nutritional status and survival time. Materials and methods: Data from two trials with advanced cancer patients were included. In both trials, patients in the intervention group received at least three times nutritional counseling and supervised training sessions. Patients in the control group continued being treated according to usual care. Nutritional status was measured using BMI, body composition and handgrip strength. Survival time was analyzed using the Cox proportional hazard model with the period between the beginning of the trial and death as underlying time scale. Results: 68 men (61.8%) and 42 women (38.2%) were randomized either to the intervention (n = 56) or the control (n = 54) group. The inter-group difference for changes in BMI and body composition was not statistically significant after 3 months. Handgrip strength improved significantly from 34.4 ± 10.2 kg to 36.3 ± 9.9 kg at 3 months in the intervention compared to 33.9 ± 9.2 kg to 34.9 ± 9.1 kg in the control group (p = 0.006). The analysis of survival time showed no inter-group difference for all patients. A detailed analysis for different diagnoses showed that in patients with lung cancer, the covariates "CRP value," "days from first diagnosis to randomization" as well as "gender" were significantly associated with survival time. Patients with higher CRP value had a shorter survival time and female patients had a shorter survival time than male patients in our analysis. In addition, patients with pancreatic cancer randomized to the control group had a 20% shorter survival time than those in the intervention group (p = 0.048). Conclusion: The pooled analysis showed a significant improvement of handgrip strength in advanced cancer patients through the implementation of a combined therapy. Handgrip strength is of prognostic significance in hospitalized patients due to its association with mortality and morbidity. However, no improvements in further tests were detected. There is great need for further investigations examining the effect of nutritional and exercise therapy on survival time with focus on different cancer diagnoses.
ABSTRACT
Traditionally, the analysis of gene regulatory regions suffered from the caveat that it was restricted to artificial contexts (e.g. reporter constructs of limited size). With the advent of the BAC recombineering technique, genomic constructs can now be generated to test regulatory elements in their endogenous environment. The expression of the transcriptional repressor brinker (brk) is negatively regulated by Dpp signaling. Repression is mediated by small sequence motifs, the silencer elements (SEs), that are present in multiple copies in the regulatory region of brk. In this work, we manipulated the SEs in the brk locus. We precisely quantified the effects of the individual SEs on the Brk gradient in the wing disc by employing a 1D data extraction method, followed by the quantification of the data with reference to an internal control. We found that mutating the SEs results in an expansion of the brk expression domain. However, even after mutating all predicted SEs, repression could still be observed in regions of maximal Dpp levels. Thus, our data point to the presence of additional, low affinity binding sites in the brk locus.
