Effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer

Potenza, Lucia; Calcabrini, Cinzia; Bellis, Roberta De; Mancini, Umberto; Polidori, Emanuela; Zeppa, Sabrina Donati; Alloni, Rossana; Cucchiarini, Luigi; Dachà, Marina

doi:10.1007/s12038-011-9064-7

Cited by 13 publications

(5 citation statements)

References 38 publications

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“…ROS production is increased upon abdominal surgery 44,45 and increases epithelial permeability 46,47 . Increased intraoperative oxidative stress was also detected in blood samples upon open but not laparoscopic surgery 48 and surgical stress also induces mitochondrial and nuclear DNA 49 . However, in the present study we did not find clear signs of oxidative stress during POI.…”

Section: Discussionmentioning

confidence: 94%

AIM2 inflammasome-derived IL-1β induces postoperative ileus in mice

Hupa

Stein

Schneider

et al. 2019

Sci Rep

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Postoperative ileus (POI) is an intestinal dysmotility frequently occurring after abdominal surgery. An orchestrated neuroimmune response within the muscularis externa (ME) involves activation of resident macrophages, enteric glia and infiltration of blood-derived leukocytes. Interleukin-1 receptor type-I (IL1R1) signalling on enteric glia has been shown to be involved in POI development. Herein we investigated the distinct role of the IL1R1 ligands interleukin (IL) -1α and IL-1β and focused on the mechanism of IL-1β production. IL-1α and IL-1β deficient mice were protected from POI. Bone-marrow transplantation studies indicated that IL-1α originated from radio-resistant cells while IL-1β was released from the radio-sensitive infiltrating leukocytes. Mouse strains deficient in inflammasome formation identified the absent in melanoma 2 (AIM2) inflammasome to be crucial for IL-1β production in POI. Mechanistically, antibiotic-treated mice revealed a prominent role of the microbiome in IL-1β production. Our study provides new insights into distinct roles of IL-1α and IL-1β signalling during POI. While IL-1α release is most likely an immediate passive response to the surgical trauma, IL-1β production depends on AIM2 inflammasome formation and the microbiome. Selective interaction in this pathway might be a promising target to prevent POI in surgical patients.

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Section: Discussionmentioning

confidence: 94%

AIM2 inflammasome-derived IL-1β induces postoperative ileus in mice

Hupa

Stein

Schneider

et al. 2019

Sci Rep

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“…23 However, these authors have summarized data for hepatic and extrahepatic metastatic sites without mentioning, whether LN were included in their study. According to the literature, the widely ranging frequency of mitochondrial genomic variation between several studies could be due to varying age compositions of the investigated populations, 39,40 surgical stress induced in possibly adherent normal colon tissue, 41 different epithelium-stroma ratios of the tumors, 42 varying proportions of tumors with advanced stages, 23,42,43 and by differences in the applied definitions and diagnostic panels. 23 Direct sequencing, which was applied in the current study, has a limited detection level, and interpretation of data might be complicated by heteroplasmy, 23 especially, if the portion of tumor DNA is less than 20% of analyzed DNA.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA alteration in primary and metastatic colorectal cancer: Different frequency and association with selected clinicopathological and molecular markers

Kleist

Meurer²,

Poetsch³

2017

Tumour Biol.

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This study attempts to determine whether primary tumor tissue could reliably represent metastatic colorectal cancer in therapy-guiding analysis of mitochondrial microsatellite instability. Therefore, we investigated the concordance of microsatellite instability in D310, D514, and D16184 (mitochondrial DNA displacement loop), and its association with selected clinical categories and KRAS/NRAS/BRAF/PIK3CA/TP53 mutation status between primary and metastatic colorectal cancer tissue from 119 patients. Displacement loop microsatellite instability was significantly more frequently seen in lymph node metastases (53.1%) compared to primary tumors (37.5%) and distant metastases (21.4%) (p = 0.0183 and p = 0.0005). The discordant rate was significantly higher in lymph node metastases/primary tumor pairs (74.6%) than in distant metastases/primary tumor pairs (52.4%) or lymph node metastases/distant metastases pairs (51.6%) (p = 0.0113 and p = 0.0261) with more gain (86.7%) than loss (61.1%) of microsatellite instability in the discordant lymph node metastases (p = 0.0024). Displacement loop instability occurred significantly more frequently in lymph node metastases and distant metastases of patients with early colorectal cancer onset age <60 years (p = 0.0122 and p = 0.0129), was found with a significant high rate in a small cohort of TP53-mutated distant metastases (p = 0.0418), and was associated with TP53 wild-type status of primary tumors (p = 0.0009), but did not correlate with KRAS, NRAS, BRAF, or PIK3CA mutations. In conclusion, mitochondrial microsatellite instability and its association with selected clinical and molecular markers are discordant in primary and metastatic colorectal cancer, which could have importance for surveillance and therapeutic strategies.

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“…Moreover it has been suggested that oxidative stress stimulates the expression of endogenous mitochondrial DNA methyltransferases (DNMTs) responsible of epigenetic modifications able to regulate the mitochondrial transcription [ 22 ] and promotes the increase of 8-hydroxy-2′-deoxyguanosine (8-oxodG) both in the nuclear and in mtDNA genome [ 23 , 24 ]. Similarly in nuclear genome the increase of 8-oxodG in CpG nucleotide [ 25 ] seems to diminish the ability of DNA methyltransferases (DNMTs) to methylate the adjacent cytosine [ 26 ].…”

Section: New Evidence Supporting the Mitochondrial Theory Of Agingmentioning

confidence: 99%

The Pleiotropic Effect of Physical Exercise on Mitochondrial Dynamics in Aging Skeletal Muscle

Barbieri

Agostini

Polidori

et al. 2015

Oxidative Medicine and Cellular Longevity

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Decline in human muscle mass and strength (sarcopenia) is one of the principal hallmarks of the aging process. Regular physical exercise and training programs are certain powerful stimuli to attenuate the physiological skeletal muscle alterations occurring during aging and contribute to promote health and well-being. Although the series of events that led to these muscle adaptations are poorly understood, the mechanisms that regulate these processes involve the “quality” of skeletal muscle mitochondria. Aerobic/endurance exercise helps to maintain and improve cardiovascular fitness and respiratory function, whereas strength/resistance-exercise programs increase muscle strength, power development, and function. Due to the different effect of both exercises in improving mitochondrial content and quality, in terms of biogenesis, dynamics, turnover, and genotype, combined physical activity programs should be individually prescribed to maximize the antiaging effects of exercise.

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Effect of surgical stress on nuclear and mitochondrial DNA from healthy sections of colon and rectum of patients with colorectal cancer

Cited by 13 publications

References 38 publications

AIM2 inflammasome-derived IL-1β induces postoperative ileus in mice

AIM2 inflammasome-derived IL-1β induces postoperative ileus in mice

Mitochondrial DNA alteration in primary and metastatic colorectal cancer: Different frequency and association with selected clinicopathological and molecular markers

The Pleiotropic Effect of Physical Exercise on Mitochondrial Dynamics in Aging Skeletal Muscle

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