Hypoxia-mediated changes in bone marrow microenvironment in breast cancer dormancy.

Breast cancer (BC) remains a clinical challenge despite improved treatments and public awareness to ensure early diagnosis. A major issue is the ability of BC cells (BCCs) to survive as dormant cancer cells in the bone marrow (BM), resulting in the cancer surviving for decades with the potential to resurge as metastatic cancer. The experimental evidence indicates similarity between dormant BCCs and other stem cells, resulting in the preponderance of data to show dormant BCCs being cancer stem cells (CSCs). The BM niche and their secretome support BCC dormancy. Lacking in the literature is a comprehensive research to describe how the hypoxic environment within the BM may influence the behavior of BCCs. This information is relevant to understand the prognosis of BC in young and aged individuals whose oxygen levels differ in BM. This review discusses the changing information on vascularity in different regions of the BM and the impact on endogenous hematopoietic stem cells (HSCs). This review highlights the necessary information to provide insights on vascularity of different BM regions on the behavior of BCCs, in particular a dormant phase. For instance, how the transcription factor HIF1-α (hypoxia-inducible factor 1 alpha), functioning as first responder under hypoxic conditions, affects the expression of specific gene networks involved in energy metabolism, cell survival, tumor invasion and angiogenesis. This enables cell fate transition and facilitates tumor heterogeneity, which in turn favors tumor progression and resistance to anticancer treatments Thus, HIF1-α could be a potential target for cancer treatment. This review describes epigenetic mechanisms involved in hypoxic responses during cancer dormancy in the bone marrow. The varied hypoxic environment in the BM is relevant to understand the complex process of the aging bone marrow for insights on breast cancer outcome between the young and aged.

Use of Heart Rate Index to Predict Oxygen Uptake - A Validation Study.

An equation that uses heart rate index (HRI) defined as HR/HRrest to predict oxygen uptake (VO2) in METs (e.g., METs = 6 × HRI - 5) has been developed retrospectively from aggregate data of 60 published studies. However, the prediction error of this model as used by an individual has not been established. Therefore, the purpose of this study was to examine the predictive validity of the HRI equation by comparing submaximal and maximal VO2 predicted by the equation (VO2-Pred) with that measured by indirect calorimetry (VO2-Meas). Sixty healthy adults (age 20.5 ± 2.4 yr., body mass 69.4 ± 13.4 kg, height 1.7 ± 0.1 m) underwent a VO2max test and an experimental trial consisting of a 15-min resting measurement and three successive 10-min treadmill exercise bouts performed at 40%, 60% and 80% of VO2max. VO2 and HR were recorded during both the submaximal and maximal exercises and used to obtain VO2-Pred and VO2-Meas for each intensity and for VO2max. Validation was carried out by paired t-test, regression analysis, and Bland-Altman plots. A modest but significant (p < 0.05) correlation was observed between VO2-Meas and VO2-Pred at 40% (r = 0.58), 60% (r = 0.53), and 80% of VO2max (r = 0.56) and at VO2max (r = 0.50). No differences between VO2-Pred and VO2-Meas were found at 40% (5.53 ± 1.21 vs. 5.28 ± 0.98 METs, respectively) of VO2max, but VO2-Pred was higher (p < 0.05) than VO2-Meas at 60% (8.42 ± 1.77 vs. 7.96 ± 1.39 METs, respectively) and 80% (10.79 ± 2.13 vs. 10.29 ± 1.81 METs, respectively) of VO2max. In contrast, VO2-Pred was lower (p < 0.05) than VO2-Meas at VO2max (12.32 ± 2.30 vs. 13.38 ± 2.24 METs, respectively). Standard errors of the estimate were 0.81, 1.20, 1.54, and 1.97 METs at 40%, 60%, 80% of VO2max and at VO2max, respectively. These results suggest that further investigation aimed to establish the accuracy of using HRI to predict VO2 is warranted.