Kepher Makambi’s research while affiliated with Georgetown University and other places

Simple Summary Non-Hispanic Black breast cancer survivors have poorer outcomes than White survivors, but the biological mechanisms underlying these disparities are unclear. We discovered novel race-based differences in systemic DNA damage and repair activity among breast cancer survivors. This finding suggests DNA damage and repair are important basic science mechanisms in cancer disparities. Abstract Non-Hispanic Black breast cancer survivors have poorer outcomes and higher mortality rates than White survivors, but systemic biological mechanisms underlying these disparities are unclear. We used circulating leukocytes as a surrogate for measuring systemic mechanisms, which might be different from processes in the target tissue (e.g., breast). We investigated race-based differences in DNA damage and repair, using a novel CometChip assay, in circulating leukocytes from breast cancer survivors who had completed primary cancer therapy and were cancer free. We observed novel race-based differences in systemic DNA damage and repair activity in cancer survivors, but not in cells from healthy volunteers. Basal DNA damage in leukocytes was higher in White survivors, but Black survivors showed a much higher induction after bleomycin treatment. Double-strand break repair activity was also significantly different between the races, with cells from White survivors showing more sustained repair activity compared to Black leukocytes. These results suggest that cancer and cancer therapy might have long-lasting effects on systemic DNA damage and repair mechanisms that differ in White survivors and Black survivors. Findings from our preliminary study in non-cancer cells (circulating leukocytes) suggest systemic effects beyond the target site, with implications for accelerated aging-related cancer survivorship disparities.

Background: Cancer treatment related fatigue (CTRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors. The primary objective of the PEDLAR study is to test the feasibility of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CTRF and improving health-related QOL among African-American breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in African-American women with breast cancer. Methods: It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group. Results: Participants in intervention group reported high satisfaction with exercise and adherence was >75% for exercise sessions. Conclusions: African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).

Background Cancer related fatigue (CRF) is one of the most debilitating side effects of adjuvant radiation therapy (RT). Several studies have found that physical activity (PA) may be an effective intervention to decrease fatigue and enhance QOL in cancer survivors. Purpose The primary objective of the PEDLAR study is to test the efficacy of an easily administered 8-week structured moderate-intensity PA intervention, delivered concurrently with RT, in reducing CRF and improving health-related QOL among AA breast cancer patients. This study is also designed to provide pilot data on the acceptability and adherence of PA interventions in AA women with breast cancer. Methods It is a prospective, 2-arm, 8-week feasibility trial. Participants are randomized to either a structured, moderate-intensity aerobic training exercise regimen concurrent with radiotherapy or a control group. Results Participants in intervention group reported high satisfaction with exercise and adherence was > 75% for exercise sessions. Conclusions African-American breast cancer patients in a moderate-intensity 75 min/wk aerobic exercise intervention had marginally lower fatigue at 8-wk follow-up compared to baseline. The control group participants had marginally higher fatigue at 8-wk follow-up compared to baseline. Participants in the intervention group reported slightly better quality of life at 8-wk follow-up compared to baseline (P = 0.06).

Background Women who engage in higher levels of exercise while trying to quit smoking have been shown to be less likely to relapse and to sustain their smoking abstinence longer. This study sought to examine the benefits of exercise for improving smoking cessation among Black women. Methods We evaluated the feasibility of a 12-week smoking and exercise intervention, Quit and Fit, tailored for Black women. All participants (intervention and control) received 12 weeks of smoking cessation counseling via telephone and 9 weeks of nicotine lozenges. Participants who were randomly assigned to the intervention condition were also assigned to a 12-week exercise group. Results Thirty-eight women were enrolled and 27 completed a 12-week follow-up assessment. Women from the intervention group were more likely to complete the 12-week follow-up assessment compared to participants in the control group (80% vs. 61%). Overall, 7 of the 38 participants (18%) were abstinent at 12 weeks (biochemically verified by expired carbon monoxide). Among the 25 women who completed the 12-week follow-up, abstinence was reported in 33% of the intervention group and 20% of the control group. Using an intent-to-treat approach, 25% of women in the intervention group were abstinent at 12 weeks (n = 5), compared to 11.1% for the control group (n = 2). These differences were not statistically significant. Conclusions The overall retention rate was 71% (27/38) at 12 weeks with higher among the intervention group (16/20; 80%) compared to the control group (11/18; 61%). The study demonstrates that it is feasible to retain African-American women in a short-term study of smoking cessation and exercise.

The empirical likelihood is a popular tool in statistics and many other fields, including regression analysis. It has the advantage of robustness against model specification and can incorporate side information to improve the estimation accuracy. There is vast literature on empirical likelihood incorporating various side information, mostly in the form of moment constraint(s). Here we study this method under two types of side information: symmetry and unimode of the underlying distribution. To our knowledge, incorporating such shape information formally via empirical likelihood has not been seen and is the goal of our study. Basic properties of the method are investigated, and extensive simulation studies are conducted to evaluate its performance and compared with the cases without such information. We found that the symmetry information can improve the variance of the estimator, while the unimode information has no such effect.

Triple negative breast cancer (TNBC), a clinically aggressive breast cancer subtype, affects 15-35% of women from Latin America. Using an approach of direct integration of copy number and global miRNA profiling data, performed simultaneously in the same tumor specimens, we identified a panel of 17 miRNAs specifically associated with TNBC of ancestrally characterized patients from Latin America, Brazil. This panel was differentially expressed between the TNBC and non-TNBC subtypes studied (p ≤ 0.05, FDR ≤ 0.25), with their expression levels concordant with the patterns of copy number alterations (CNAs), present mostly frequent at 8q21.3-q24.3, 3q24-29, 6p25.3-p12.2, 1q21.1-q44, 5q11.1-q22.1, 11p13-p11.2, 13q12.11-q14.3, 17q24.2-q25.3 and Xp22.33-p11.21. The combined 17 miRNAs presented a high power (AUC = 0.953 (0.78-0.99);95% CI) in discriminating between the TNBC and non-TNBC subtypes of the patients studied. In addition, the expression of 14 and 15 of the 17miRNAs was significantly associated with tumor subtype when adjusted for tumor stage and grade, respectively. In conclusion, the panel of miRNAs identified demonstrated the impact of CNAs in miRNA expression levels and identified miRNA target genes potentially affected by both CNAs and miRNA deregulation. These targets, involved in critical signaling pathways and biological functions associated specifically with the TNBC transcriptome of Latina patients, can provide biological insights into the observed differences in the TNBC clinical outcome among racial/ethnic groups, taking into consideration their genetic ancestry. www.oncotarget.com

Batched data is a type of data where each observed data value is the sum of a number of grouped (batched) latent ones obtained under different conditions. Batched data arises in various practical backgrounds and is often found in social studies and management sector. The analysis of such data is analytically challenging due to its structural complexity. In this article, we describe how to analyze batched service time data, estimate the mean and variance of each batch that are latent. We in particular focus on the situation when the observed total time includes an unknown proportion of non-service time. To address this problem, we propose a Gaussian model for efficiency as well as a semi-parametric kernel density model for robustness. We evaluate the performance of both proposed methods through simulation studies and then applied our methods to analyze a batched data.