scholarly journals The Interplay of Reactive Oxygen Species, Hypoxia, Inflammation, and Sirtuins in Cancer Initiation and Progression

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Marco Tafani ◽  
Luigi Sansone ◽  
Federica Limana ◽  
Tania Arcangeli ◽  
Elena De Santis ◽  
...  
Keyword(s):  
Natural History ◽  
Gene Mutations ◽  
Suppressor Gene ◽  
Malignant Progression ◽  
Initial Growth ◽  
Cancer Hallmarks ◽  
Beneficial Effects ◽  
Cancer Initiation ◽  
History Of

The presence of ROS is a constant feature in living cells metabolizing O2. ROS concentration and compartmentation determine their physiological or pathological effects. ROS overproduction is a feature of cancer cells and plays several roles during the natural history of malignant tumor. ROS continuously contribute to each step of cancerogenesis, from theinitiationto themalignant progression, acting directly or indirectly. In this review, we will (a) underline the role of ROS in the pathway leading a normal cell to tumor transformation and progression, (b) define the multiple roles of ROS during the natural history of a tumor, (c) conciliate many conflicting data about harmful or beneficial effects of ROS, (d) rethink the importance of oncogene and tumor suppressor gene mutations in relation to the malignant progression, and (e) collocate all the cancer hallmarks in a mechanistic sequence which could represent a “physiological” response to the initial growth of a transformed stem/pluripotent cell, defining also the role of ROS in each hallmark. We will provide a simplified sketch about the relationships between ROS and cancer. The attention will be focused on the contribution of ROS to the signaling of HIF, NFκB, and Sirtuins as a leitmotif of cancer initiation and progression.

scholarly journals The longitudinal dynamics and natural history of clonal haematopoiesis

2021 ◽  
Author(s):  
Margarete A Fabre ◽  
José Guilherme de Almeida ◽  
Edoardo Fiorillo ◽  
Emily Mitchell ◽  
Aristi Damaskou ◽  
...  
Keyword(s):  
Natural History ◽  
Growth Rates ◽  
Time Series Data ◽  
Clonal Selection ◽  
Gene Mutations ◽  
Malignant Progression ◽  
Series Data ◽  
Older Individuals ◽  
History Of ◽  
Myeloid Neoplasia

Human cells acquire somatic mutations throughout life, some of which can drive clonal expansion. Such expansions are frequent in the haematopoietic system of healthy individuals and have been termed clonal haematopoiesis (CH). While CH predisposes to myeloid neoplasia and other diseases, we have limited understanding of how and when CH develops, what factors govern its behaviour, how it interacts with ageing and how these variables relate to malignant progression. Here, we track 697 CH clones from 385 individuals aged 55 or older over a median of 13 years. We find that 92.4% of clones expanded at a stable exponential rate over the study period, with different mutations driving substantially different growth rates, ranging from 5% (DNMT3A, TP53) to over 50%/yr (SRSF2-P95H). Growth rates of clones with the same mutation differed by approximately +/-5%/yr, proportionately impacting "slow" drivers more substantially. By combining our time-series data with phylogenetic analysis of 1,731 whole genome-sequenced haematopoietic colonies from 7 older individuals, we reveal distinct patterns of lifelong clonal behaviour. DNMT3A-mutant clones preferentially expanded early in life and displayed slower growth in old age, in the context of an increasingly competitive oligoclonal landscape. By contrast, splicing gene mutations only drove expansion later in life, while growth of TET2-mutant clones showed minimal age-dependency. Finally, we show that mutations driving faster clonal growth carry a higher risk of malignant progression. Our findings characterise the lifelong natural history of CH and give fundamental insights into the interactions between somatic mutation, ageing and clonal selection.

scholarly journals Natural History of Excessive Daytime Sleepiness: Role of Obesity, Weight Loss, Depression, and Sleep Propensity

SLEEP ◽  
2015 ◽  
Vol 38 (3) ◽  
pp. 351-360 ◽  
Author(s):  
Julio Fernandez-Mendoza ◽  
Alexandros N. Vgontzas ◽  
Ilia Kritikou ◽  
Susan L. Calhoun ◽  
Duanping Liao ◽  
...  
Keyword(s):  
Weight Loss ◽  
Natural History ◽  
Excessive Daytime Sleepiness ◽  
Daytime Sleepiness ◽  
History Of ◽  
Sleep Propensity

The natural history of sleep disturbance among OEF/OIF veterans with TBI and PTSD and the role of proxy variables in its measurement

2017 ◽  
Vol 96 ◽  
pp. 60-66 ◽  
Author(s):  
Paul R. King ◽  
Kerry T. Donnelly ◽  
Gary Warner ◽  
Michael Wade ◽  
Wilfred R. Pigeon
Keyword(s):  
Natural History ◽  
Sleep Disturbance ◽  
Proxy Variables ◽  
History Of

scholarly journals Role of Endothelial Shear Stress in the Natural History of Coronary Atherosclerosis and Vascular Remodeling

2007 ◽  
Vol 49 (25) ◽  
pp. 2379-2393 ◽  
Author(s):  
Yiannis S. Chatzizisis ◽  
Ahmet Umit Coskun ◽  
Michael Jonas ◽  
Elazer R. Edelman ◽  
Charles L. Feldman ◽  
...  
Keyword(s):  
Shear Stress ◽  
Natural History ◽  
Vascular Remodeling ◽  
Coronary Atherosclerosis ◽  
History Of ◽  
Endothelial Shear Stress

Effects of long-term chloroquine administration on the natural history of aortic aneurysms in mice

2015 ◽  
Vol 93 (8) ◽  
pp. 641-648 ◽  
Author(s):  
Azza Ramadan ◽  
Mark D. Wheatcroft ◽  
Adrian Quan ◽  
Krishna K. Singh ◽  
Fina Lovren ◽  
...  
Keyword(s):  
Natural History ◽  
Thrombus Formation ◽  
Aortic Aneurysms ◽  
Ang Ii ◽  
Abdominal Aortic ◽  
Suprarenal Aorta ◽  
History Of ◽  
Categorical Distribution

Autophagy regulates cellular homeostasis and integrates the cellular pro-survival machinery. We investigated the role of autophagy in the natural history of murine abdominal aortic aneurysms (AAA). ApoE−/− mice were implanted with saline- or angiotensin II (Ang-II)-filled miniosmotic pumps then treated with either the autophagy inhibitor chloroquine (CQ; 50 mg·(kg body mass)–1·day–1, by intraperitoneal injection) or saline. Ang-II-elicited aneurysmal expansion of the suprarenal aorta coupled with thrombus formation were apparent 8 weeks later. CQ had no impact on the incidence (50% for Ang-II compared with 46.2% for Ang-II + CQ; P = NS) and categorical distribution of aneurysms. The markedly reduced survival rate observed with Ang-II (57.1% for Ang-II compared with 100% for saline; P < 0.05) was unaffected by CQ (61.5% for Ang-II + CQ; P = NS compared with Ang-II). CQ did not affect the mean maximum suprarenal aortic diameter (1.91 ± 0.19 mm for Ang-II compared with 1.97 ± 0.21 mm for Ang-II + CQ; P = NS). Elastin fragmentation, collagen accumulation, and smooth muscle attrition, which were higher in Ang-II-treated mice, were unaffected by CQ treatment. Long-term CQ administration does not affect the natural history and prognosis of experimental AAA, suggesting that global loss of autophagy is unlikely to be a causal factor in the development of aortic aneurysms. Manipulation of autophagy as a mechanism to reduce AAA may need re-evaluation.

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