Radiation therapy for cancer is potentially associated with reduced growth of concomitant abdominal aortic aneurysm.

PURPOSE: Co-prevalence of abdominal aortic aneurysm (AAA) and cancer poses a unique challenge in medical care since both diseases and their respective therapies might interact. Recently, reduced AAA growth rates were observed in cancer patients that received radiation therapy (RT). The purpose of this study was to perform a fine-grained analysis of the effects of RT on AAA growth with respect to direct (infield) and out-of-field (outfield) radiation exposure, and radiation dose-dependency. METHODS: A retrospective single-center analysis identified patients with AAA, cancer, and RT. Clinical data, radiation plans, and aneurysm diameters were analyzed. The total dose of radiation to each aneurysm was computed. AAA growth under infield and outfield exposure was compared to patients with AAA and cancer that did not receive RT (no-RT control) and to an external noncancer AAA reference cohort. RESULTS: Between 2003 and 2020, a total of 38 AAA patients who had received well-documented RT for their malignancy were identified. AAA growth was considerably reduced for infield patients (n = 18) compared to outfield patients (n = 20), albeit not significantly (0.8 ± 1.0 vs. 1.3 ± 1.6 mm/year, p = 0.28). Overall, annual AAA growth in RT patients was lower compared to no-RT control patients (1.1 ± 1.5 vs. 1.8 ± 2.2 mm/year, p = 0.06) and significantly reduced compared to the reference cohort (1.1 ± 1.5 vs. 2.7 ± 2.1 mm/year, p < 0.001). The pattern of AAA growth reduction due to RT was corroborated in linear regression analyses correcting for initial AAA diameter. A further investigation with respect to dose-dependency of radiation effects on AAA growth, however, revealed no apparent association. CONCLUSION: In this study, both infield and outfield radiation exposure were associated with reduced AAA growth. This finding warrants further investigation, both in a larger scale clinical cohort and on a molecular level.

Concomitantly discovered visceral artery aneurysms do rarely grow during cancer therapy.

Visceral artery aneurysms (VAA) are a rare entity of arterial aneurysms with the imminent threat of rupture. The impact of cancer and chemotherapy on the growth of VAAs is unknown. A retrospective dual center cohort study of patients with concomitant VAA and different types of cancer was conducted and the impact of various chemotherapeutic agents on VAA growth was studied by sequential CT analysis. For comparison, a non-cancer all comer cohort with VAAs and no cancer was studied to compare different growth rates. The primary endpoint was aneurysm progress or regression >1.75 mm. Chi-square test, Fisher's exact test and Mann-Whitney test was used for statistical comparison. In the 17-year-period from January 2003 to March 2020, 59 patients with 30 splenic artery aneurysms, 14 celiac trunk aneurysms, 11 renal artery aneurysms and 4 other VAA and additional malignancy were identified. 20% of patients suffered from prostate cancer, the rest were heterogeneous. The most prevalent chemotherapies were alkylating agents (23%), antimetabolites (14%) and mitose inhibitors (10%). Eight patients had relevant growth of their VAA and one patient showed diameter regression (average growth rate 0.1 ± 0.5 mm/year). Twenty-nine patients with 14 splenic, 11 RAAs (seven right) and 4 celiac trunk aneurysms were available in the non-cancer comparison cohort (average growth rate 0.5 ± 0.9 mm/year, p = 0.058). However, the growth rate of patients receiving operative treatment for relevant VAA growth was significantly higher (p = 0.004). VAAs grow rarely, and rather slow. Cancer and/or chemotherapy do not significantly influence the annual growth rate. Additional control examinations seem unnecessary.

Canalization of gene expression is a major signature of regulatory cold adaptation in temperate Drosophila melanogaster.

BACKGROUND: Transcriptome analysis may provide means to investigate the underlying genetic causes of shared and divergent phenotypes in different populations and help to identify potential targets of adaptive evolution. Applying RNA sequencing to whole male Drosophila melanogaster from the ancestral tropical African environment and a very recently colonized cold-temperate European environment at both standard laboratory conditions and following a cold shock, we seek to uncover the transcriptional basis of cold adaptation. RESULTS: In both the ancestral and the derived populations, the predominant characteristic of the cold shock response is the swift and massive upregulation of heat shock proteins and other chaperones. Although we find ~25 % of the genome to be differentially expressed following a cold shock, only relatively few genes (n = 16) are up- or down-regulated in a population-specific way. Intriguingly, 14 of these 16 genes show a greater degree of differential expression in the African population. Likewise, there is an excess of genes with particularly strong cold-induced changes in expression in Africa on a genome-wide scale. CONCLUSIONS: The analysis of the transcriptional cold shock response most prominently reveals an upregulation of components of a general stress response, which is conserved over many taxa and triggered by a plethora of stressors. Despite the overall response being fairly similar in both populations, there is a definite excess of genes with a strong cold-induced fold-change in Africa. This is consistent with a detrimental deregulation or an overshooting stress response. Thus, the canalization of European gene expression might be responsible for the increased cold tolerance of European flies.

Inter- and intraspecific variation in Drosophila genes with sex-biased expression.

Genes with sexually dimorphic expression (sex-biased genes) often evolve rapidly and are thought to make an important contribution to reproductive isolation between species. We examined the molecular evolution of sex-biased genes in Drosophila melanogaster and D. ananassae, which represent two independent lineages within the melanogaster group. We find that strong purifying selection limits protein sequence variation within species, but that a considerable fraction of divergence between species can be attributed to positive selection. In D. melanogaster, the proportion of adaptive substitutions between species is greatest for male-biased genes and is especially high for those on the X chromosome. In contrast, male-biased genes do not show unusually high variation within or between populations. A similar pattern is seen at the level of gene expression, where sex-biased genes show high expression divergence between species, but low divergence between populations. In D. ananassae, there is no increased rate of adaptation of male-biased genes, suggesting that the type or strength of selection acting on sex-biased genes differs between lineages.