The aim of this study is to review accelerometer wear methods and correlations between accelerometry and physical activity questionnaire data, depending on participant characteristics.
We included 57 ...articles about physical activity measurement by accelerometry and questionnaires. Criteria were to have at least 100 participants of at least 18 years of age with manuscripts available in English. Accelerometer wear methods were compared. Spearman and Pearson correlation coefficients between questionnaires and accelerometers and differences between genders, age categories, and body mass index (BMI) categories were assessed.
In most investigations, requested wear time was seven days during waking hours and devices were mostly attached on hips with waist belts. A minimum of four valid days with wear time of at least ten hours per day was required in most studies. Correlations (r = Pearson, ρ = Spearman) of total questionnaire scores against accelerometer measures across individual studies ranged from r = 0.08 to ρ = 0.58 (P < 0.001) for men and from r = -0.02 to r = 0.49 (P < 0.01) for women. Correlations for total physical activity among participants with ages ≤65 ranged from r = 0.04 to ρ = 0.47 (P < 0.001) and from r = 0.16 (P = 0.02) to r = 0.53 (P < 0.01) among the elderly (≥65 years). Few studies investigated stratification by BMI, with varying cut points and inconsistent results.
Accelerometers appear to provide slightly more consistent results in relation to self-reported physical activity among men. Nevertheless, due to overall limited consistency, different aspects measured by each method, and differences in the dimensions studied, it is advised that studies use both questionnaires and accelerometers to gain the most complete physical activity information.
Background The association between body mass index as a measure of obesity and rectal cancer outcomes has been inconsistent. Radiologic measures of visceral adiposity using CT scans have not been ...well characterized among rectal cancer patients. The objective of this study was to examine quantitative radiologic measures of visceral obesity compared with body mass index in predicting patient outcomes among patients undergoing neoadjuvant chemoradiation and resection for locally advanced rectal cancers. Study Design We identified 99 rectal adenocarcinoma patients treated with neoadjuvant chemoradiation and surgical resection. Visceral and subcutaneous fat areas, as well as perinephric fat thickness (PNF), were recorded and categorized as obese (body mass index ≥30, visceral fat area to subcutaneous fat area ratio V/S ≥0.4, or median PNF). The Kaplan-Meier method, log-rank test, and Cox proportional hazards models evaluated overall and disease-free survival differences by adiposity. Results Viscerally obese rectal cancer patients (V/S >0.4 or PNF) were more likely to be older, male, and have pre-existing obesity-related conditions (eg, diabetes, hypertension, and/or hypercholesterolemia). Elevated V/S or PNF was associated with shorter disease-free survival (p = 0.02) or overall survival time (p = 0.047), respectively. Among patients with well to moderately differentiated tumors, visceral obesity was associated with poorer disease-free survival (V/S >0.4: adjusted hazard ratio = 5.0; 95% CI, 1.2–22.0). Conclusions Visceral fat area to subcutaneous fat area ratio and PNF were strongly associated with key preoperative metabolic comorbidities, and body mass index was not. Findings suggests that elevated visceral adiposity was associated with an increased risk of recurrence, which was most evident among patients with well to moderately differentiated tumors and those with incomplete response to neoadjuvant chemoradiation treatment. Quantitative measures of visceral adiposity warrant large-scale prospective evaluation.
Patients with head and neck squamous cell carcinoma (HNSCC) who actively smoke during treatment have worse survival compared with never-smokers and former-smokers. We hypothesize the poor prognosis ...in tobacco smokers with HNSCC is, at least in part, due to ongoing suppression of immune response. We characterized the tumor immune microenvironment (TIM) of HNSCC in a retrospective cohort of 177 current, former, and never smokers.
Tumor specimens were subjected to analysis of CD3, CD8, FOXP3, PD-1, PD-L1, and pancytokeratin by multiplex immunofluorescence, whole-exome sequencing, and RNA sequencing. Immune markers were measured in tumor core, tumor margin, and stroma.
Our data indicate that current smokers have significantly lower numbers of CD8
cytotoxic T cells and PD-L1
cells in the TIM compared with never- and former-smokers. While tumor mutation burden and mutant allele tumor heterogeneity score do not associate with smoking status, gene-set enrichment analyses reveal significant suppression of IFNα and IFNγ response pathways in current smokers. Gene expression of canonical IFN response chemokines,
,
, and
, are lower in current smokers than in former smokers, suggesting a mechanism for the decreased immune cell migration to tumor sites.
These results suggest active tobacco use in HNSCC has an immunosuppressive effect through inhibition of tumor infiltration of cytotoxic T cells, likely as a result of suppression of IFN response pathways. Our study highlights the importance of understanding the interaction between smoking and TIM in light of emerging immune modulators for cancer management.
Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating ...different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery.
Aberrant DNA methylation has been observed in cervical cancer; however, most studies have used non-quantitative approaches to measure DNA methylation. The objective of this study was to quantify ...methylation within a select panel of genes previously identified as targets for epigenetic silencing in cervical cancer and to identify genes with elevated methylation that can distinguish cancer from normal cervical tissues. We identified 49 women with invasive squamous cell cancer of the cervix and 22 women with normal cytology specimens. Bisulfite-modified genomic DNA was amplified and quantitative pyrosequencing completed for 10 genes (APC, CCNA, CDH1, CDH13, WIF1, TIMP3, DAPK1, RARB, FHIT, and SLIT2). A Methylation Index was calculated as the mean percent methylation across all CpG sites analyzed per gene (~4-9 CpG site) per sequence. A binary cut-point was defined at >15% methylation. Sensitivity, specificity and area under ROC curve (AUC) of methylation in individual genes or a panel was examined. The median methylation index was significantly higher in cases compared to controls in 8 genes, whereas there was no difference in median methylation for 2 genes. Compared to HPV and age, the combination of DNA methylation level of DAPK1, SLIT2, WIF1 and RARB with HPV and age significantly improved the AUC from 0.79 to 0.99 (95% CI: 0.97-1.00, p-value = 0.003). Pyrosequencing analysis confirmed that several genes are common targets for aberrant methylation in cervical cancer and DNA methylation level of four genes appears to increase specificity to identify cancer compared to HPV detection alone. Alterations in DNA methylation of specific genes in cervical cancers, such as DAPK1, RARB, WIF1, and SLIT2, may also occur early in cervical carcinogenesis and should be evaluated.
Patients consented to biobanking studies typically do not specify research conducted on their samples and data. Our objective was to gauge cancer biobanking participant preferences on research ...topics. Patient-participants of a biobanking study at a comprehensive cancer center who had an appointment within the last 5 years, had a valid email address, and with a last known vital status of alive, were emailed a newsletter containing a link to a survey about preferences and priorities for research. The survey assessed demographics and research interest in three domains: cancer site, cancer-related topics, and issues faced by cancer patients. 37,384 participants were contacted through email to participate in the survey. 16,158 participants (43.2%) opened the email, 1,626 (4.3% overall, 10% of those who opened the email) completed the survey, and 1,291 (79.4% of those who completed the survey) selected at least one research priority. Among those who selected at least one research priorities for cancer-relevant topics, the most commonly selected were cancer treatment (66%), clinical trials (54%), and cancer prevention (53%). Similarly, the most selected priorities for cancer-related issues faced by patients were physical side effects of cancer (57%), talking to the oncologist (53%), and emotional challenges due to cancer (47%). Differences by gender were observed, with females reporting more interest in research generally. Cancer patients participating in a biobanking protocol prioritized research on treatments, prevention and side effects, which varied by gender.
HPV infection results in changes in host gene methylation which, in turn, are thought to contribute to the neoplastic progression of HPV-associated cancers. The objective of this study was to ...identify joint and disease-specific genome-wide methylation changes in anal and cervical cancer as well as changes in high-grade pre-neoplastic lesions. Formalin-fixed paraffin-embedded (FFPE) anal tissues (n = 143; 99% HPV+) and fresh frozen cervical tissues (n = 28; 100% HPV+) underwent microdissection, DNA extraction, HPV genotyping, bisulfite modification, DNA restoration (FFPE) and analysis by the Illumina HumanMethylation450 Array. Differentially methylated regions (DMR; t test q<0.01, 3 consecutive significant CpG probes and mean Δβ methylation value>0.3) were compared between normal and cancer specimens in partial least squares (PLS) models and then used to classify anal or cervical intraepithelial neoplasia-3 (AIN3/CIN3). In AC, an 84-gene PLS signature (355 significant probes) differentiated normal anal mucosa (NM; n = 9) from AC (n = 121) while a 36-gene PLS signature (173 significant probes) differentiated normal cervical epithelium (n = 10) from CC (n = 9). The CC progression signature was validated using three independent publicly available datasets (n = 424 cases). The AC and CC progression PLS signatures were interchangeable in segregating normal, AIN3/CIN3 and AC and CC and were found to include 17 common overlapping hypermethylated genes. Moreover, these signatures segregated AIN3/CIN3 lesions similarly into cancer-like and normal-like categories. Distinct methylation changes occur across the genome during the progression of AC and CC with overall similar profiles and add to the evidence suggesting that HPV-driven oncogenesis may result in similar non-random methylomic events. Our findings may lead to identification of potential epigenetic drivers of HPV-associated cancers and also, of potential markers to identify higher risk pre-cancerous lesions.
Rolling is a critical step of infant development, encouraging muscle coordination and enabling independent exploration. Understanding muscle activity during infant rolling movements on a flat surface ...is necessary to more fully characterize how the rolling milestone is achieved. The purpose of this study was to determine infants' muscle activation throughout roll initiation for six previously established coordinated movements. Thirty-eight healthy infants (age: 6.5 ± 0.7 months; 23M/15F) were enrolled in this IRB-approved in-vivo biomechanics study. Surface electromyography sensors recorded muscle utilization from the erector spinae, abdominal muscles, quadriceps, and hamstrings while infants rolled. Each rolling movement was categorized as one of six roll types, and the mean muscle activity was analyzed. All roll types required initial activation of all measured muscle groups. Movements featuring axial rotation of the torso relative to the pelvis required highly active erector spinae muscles. Movements featuring trunk and hip flexion required highly active abdominal muscles. Infants used distinct coordinated muscle activations to achieve the six different roll types on a flat surface. A foundational understanding of the different muscle activation patterns required during infant rolling will provide crucial insight into motor development. This study quantified muscle coordination required of infants to achieve rolling on a firm flat surface. Previous research indicates that the mechanical environment in which an infant is placed impacts muscle activity and body position during normal lying. Therefore, future work should explore if mechanical environments that differ from a flat and firm surface also influence these coordinated movements and muscle activations.
TRIM29 (ATDC) exhibits a contextual function in cancer, but seems to exert a tumor-suppressor role in breast cancer. Here, we show that TRIM29 is often silenced in primary breast tumors and cultured ...tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial-mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene-expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival, increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT.
Background
Quantitative computed tomography (CT) assessment of visceral adiposity may be superior to body mass index (BMI) as a predictor of surgical morbidity. We sought to examine the association ...of CT measures of obesity and BMI with short-term postoperative outcomes in colon cancer patients.
Methods
In this retrospective study, 110 patients treated with colectomy for stage I–III colon cancer were classified as obese or non-obese by preoperative CT-based measures of adiposity or BMI obese: BMI ≥ 30 kg/m
2
, visceral fat area (VFA) to subcutaneous fat area ratio (
V
/
S
) ≥0.4, and VFA > 100 cm
2
. Postoperative morbidity and mortality rates were compared.
Results
Obese patients, by
V
/
S
and VFA but not BMI, were more likely to be male and have preexisting hypertension and diabetes. The overall complication rate was 25.5%, and there were no mortalities. Obese patients by VFA (with a trend for
V
/
S
but not BMI) were more likely to develop postoperative complications as compared to patients classified as non-obese: VFA (30.5 vs.10.7%,
p =
0.03),
V
/
S
(29.2 vs. 9.5%,
p
= 0.05), and BMI (32.4 vs. 21.9%,
p
= 0.23).
Conclusions
Elevated visceral obesity quantified by CT is associated with the presence of key metabolic comorbidities and increased postoperative morbidity and may be superior to BMI for risk stratification.
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