Background: Older cancer survivors are at risk of the development or worsening of both age- and treatment-related morbidity. Sedentary behavior increases the risk of or exacerbates these chronic conditions. Light-intensity physical activity (LPA) is more common in older adults and is associated with better health and well-being. Thus, replacing sedentary time with LPA may provide a more successful strategy to reduce sedentary time and increase physical activity. Objective: This study primarily aims to evaluate the feasibility, acceptability, and preliminary efficacy of a home-based mobile health (mHealth) intervention to interrupt and replace sedentary time with LPA (standing and stepping). The secondary objective of this study is to examine changes in objective measures of physical activity, physical performance, and self-reported quality of life. Methods: Overall, 54 cancer survivors (aged 60-84 years) were randomized in a 1:1:1 allocation to the tech support intervention group, tech support plus health coaching intervention group, or waitlist control group. Intervention participants received a Jawbone UP2 activity monitor for use with their smartphone app for 13 weeks. Tech support and health coaching were provided via 5 telephone calls during the 13-week intervention. Sedentary behavior and physical activity were objectively measured using an activPAL monitor for 7 days before and after the intervention. Results: Participants included survivors of breast cancer (21/54, 39%), prostate cancer (16/54, 30%), and a variety of other cancer types; a mean of 4.4 years (SD 1.6) had passed since their cancer diagnosis. Participants, on average, were 70 years old (SD 4.8), 55% (30/54) female, 24% (13/54) Hispanic, and 81% (44/54) overweight or obese. Malfunction of the Jawbone trackers occurred in one-third of the intervention group, resulting in enrollment stopping at 54 rather than the initial goal of 60 participants. Despite these technical issues, the retention in the intervention was high (47/54, 87%). Adherence was high for wearing the tracker (29/29, 100%) and checking the app daily (28/29, 96%) but low for specific aspects related to the sedentary features of the tracker and app (21%-25%). The acceptability of the intervention was moderately high (81%). There were no significant between-group differences in total sedentary time, number of breaks, or number of prolonged sedentary bouts. There were no significant between-group differences in physical activity. The only significant within-group change occurred within the health coaching group, which increased by 1675 daily steps (95% CI 444-2906; P=.009). This increase was caused by moderate-intensity stepping rather than light-intensity stepping (+15.2 minutes per day; 95% CI 4.1-26.2; P=.008). Conclusions: A home-based mHealth program to disrupt and replace sedentary time with stepping was feasible among and acceptable to older cancer survivors. Future studies are needed to evaluate the optimal approach for replacing sedentary behavior with standing and/or physical activity in this population. Trial Registration: ClinicalTrials.gov NCT03632694; https://clinicaltrials.gov/ct2/show/NCT03632694

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with inferior outcome compared with that of B cell ALL. Here, we show that Runt-related transcription factor 2 (RUNX2) was upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or an immature immunophenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, where it reciprocally bound the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 was required for survival of immature and KMT2A-R T-ALL cells in vitro and in vivo. We report direct transcriptional regulation of CXCR4 signaling by RUNX2, thereby promoting chemotaxis, adhesion, and homing to medullary and extramedullary sites. RUNX2 enabled these energy-demanding processes by increasing metabolic activity in T-ALL cells through positive regulation of both glycolysis and oxidative phosphorylation. Concurrently, RUNX2 upregulation increased mitochondrial dynamics and biogenesis in T-ALL cells. Finally, as a proof of concept, we demonstrate that immature and KMT2A-R T-ALL cells were vulnerable to pharmacological targeting of the interaction between RUNX2 and its cofactor CBFβ. In conclusion, we show that RUNX2 acts as a dependency factor in high-risk subtypes of human T-ALL through concomitant regulation of tumor metabolism and leukemic cell migration.

The tumor microenvironment for epithelial ovarian cancer is complex and rich in bioactive molecules that modulate cell-cell interactions and stimulate numerous signal transduction cascades. These signals ultimately modulate all aspects of tumor behavior including progression, metastasis and therapeutic response. Many of the signaling pathways converge on the small GTPase Ras-related C3 botulinum toxin substrate (Rac)1. In addition to regulating actin cytoskeleton remodeling necessary for tumor cell adhesion, migration and invasion, Rac1 through its downstream effectors, regulates cancer cell survival, tumor angiogenesis, phenotypic plasticity, quiescence, and resistance to therapeutics. In this review we discuss evidence for Rac1 activation within the ovarian tumor microenvironment, mechanisms of Rac1 dysregulation as they apply to ovarian cancer, and the potential benefits of targeting aberrant Rac1 activity in this disease. The potential for Rac1 contribution to extraperitoneal dissemination of ovarian cancer is addressed.

Adenoid cystic carcinoma (ACC) is an aggressive salivary gland tumor that frequently displays perineural invasion and is often associated with translocations or overexpression of the MYB oncogene. Detailed analyses of MYB transcripts from ACC patient samples revealed that ACC tumors utilize an alternative MYB promoter, which is rarely used in normal cells or other tumor types. The alternative promoter transcripts produce N-terminally truncated Myb proteins lacking a highly conserved and phosphorylated domain, which includes the pS11 epitope that is frequently used to detect Myb proteins. In RNA-seq assays, Myb isoforms lacking the N-terminal domain displayed unique transcriptional activities, regulating many genes differently than full-length Myb. Thus, a regulatory pathway unique to ACC activates the alternative MYB promoter, leading to the production of a truncated Myb protein with altered transcriptional activities. This could provide new therapeutic opportunities for ACC patients.

Non-coding RNAs occupy a significant fraction of the human genome. Their biological significance is backed up by a plethora of emerging evidence. One of the most robust approaches to demonstrate non-coding RNA’s biological relevance is through their prognostic value. Using the rich gene expression data from The Cancer Genome Altas (TCGA), we designed Advanced Expression Survival Analysis (AESA), a web tool which provides several novel survival analysis approaches not offered by previous tools. In addition to the common single-gene approach, AESA computes the gene expression composite score of a set of genes for survival analysis and utilizes permutation test or cross-validation to assess the significance of log-rank statistic and the degree of over-fitting. AESA offers survival feature selection with post-selection inference and utilizes expanded TCGA clinical data including overall, disease-specific, disease-free, and progression-free survival information. Users can analyze either protein-coding or non-coding regions of the transcriptome. We demonstrated the effectiveness of AESA using several empirical examples. Our analyses showed that non-coding RNAs perform as well as messenger RNAs in predicting survival of cancer patients. These results reinforce the potential prognostic value of non-coding RNAs. AESA is developed as a module in the freely accessible analysis suite MutEx.