Proteomic Analysis of Plasma Reveals Fat Mass Influences Cancer-related Pathways in Healthy Humans Fed Controlled Diets Differing in Glycemic Load

The carbohydrates and related biomarkers (CARB) study was a randomized, controlled crossover feeding trial, where 80 normal-weight or overweight/obese participants each consumed two controlled diets differing in glycemic load to investigate if such diets were associated with modulation of cancer risk biomarkers. In this study, the authors utilized a proteomics approach to investigate if the consumption of a low- or high-glycemic diet altered proteins in plasma taken from the participants in the CARB trial. Only among participants with a high body fat mass, the researchers observed overrepresentation of cancer-related pathways involved with DNA repair, DNA replication, cell cycle, the adaptive immune system, and WNT signaling. The authors conclude that the physiological impact of consuming a low- or high-glycemic diet may depend on an individual’s fat mass, and that dietary recommendations related to cancer prevention should consider an individual’s adiposity. This article was featured on the cover of this issue.

Providing Higher Resolution Indicators of Rurality in the Surveillance, Epidemiology, and End Results (SEER) Database: Implications for Patient Privacy and Research

The addition of rurality information at the census tract level into the Surveillance, Epidemiology, and End Results (SEER) database would improve etiologic and surveillance studies, but whether this addition would increase the risk of revealing individual patients’ identity, especially since a census tract-based socioeconomic status (SES) quintile has already been added, has yet to be determined. In this study, the authors calculated the percentage of census tracts and cancer cases that could be uniquely identified following the addition of two indicators of census tract-level rurality, the U.S. Department of Agriculture’s Rural Urban Commuting Area (RUCA) codes and the U.S. Census data on the percentage of the population living in nonurban areas, into the SEER database along with a census-tract SES variable. The researchers found that the risk of disclosure was low; less than 0.03 percent of census tracts and less than 0.03 percent of cancer cases were uniquely identifiable. The authors note that a specialized SEER 18 database that includes RUCA and Census rurality measures is available for research use upon request. This article was highlighted in this issue.

Therapeutic Effect of Y-27632 on Tumorigenesis and Cisplatin-induced Peripheral Sensory Loss Through RhoA-NF-κB

Even though cisplatin is an effective, first-line chemotherapeutic option, it has a high level of toxicity which can culminate in chemotherapy-induced peripheral neuropathy (CIPN), negatively impacting a patient’s quality of life and potentially requiring the reduction or cessation of treatment. In this study, the authors created an immunocompetent tumor-bearing CIPN mouse model and evaluated tumor and host responses to a therapeutic combination consisting of cisplatin and Y-27632, an inhibitor of the Rho/ROCK pathway. Not only did Y-27632 enhance the antineoplastic effects of cisplatin in both in vitro and in vivo settings, it also prevented the cisplatin-induced loss of epidermal nerve fibers, protecting tumor-bearing mice from reduced touch sensation brought on by cisplatin treatment. Further, proteomic analyses revealed that Y-27632 decreased NF-κB hyperactivation in footpad tissues, suggesting that targeting the RhoA-NF-κB axis may help to ameliorate CIPN. This article was highlighted and featured on the cover of this issue.

Tumor Angiogenesis is Differentially Regulated by Phosphorylation of Endothelial Cell Focal Adhesion Kinase Tyrosines-397 and -861

Focal adhesion kinase (FAK) is an ubiquitously expressed tyrosine kinase that is essential for angiogenesis, yet how the phosphorylation of FAK at tyrosine residues Y397 and Y861 regulate tumor angiogenesis has not been fully explored. In this study, the authors studied mice with inducible endothelial cell-specific non-phosphorylatable tyrosine mutations. Following the subcutaneous injection of melanoma or lung carcinoma cells, the researchers found that mice with homozygous Y397F FAK mutations had reduced tumor growth and angiogenesis as compared with controls, but mice with homozygous Y861F FAK mutations had normal tumor growth and only a transient reduction of angiogenesis. Mechanistically, the researchers found that FAK-Y397F endothelial cells had disrupted FAK-Src interactions, increased expression of Tie-2, and decreased activation of β1-integrin, while FAK-Y861F endothelial cells maintained FAK-Src interactions, had decreased expression of Tie-2, and had enhanced activation of β1-integrin. These results suggest that the phosphorylation of these two tyrosine residues differentially regulate tumor angiogenesis. This article was featured on the cover of this issue.

Volumetric Optoacoustic Imaging Unveils High-Resolution Patterns of Acute and Cyclic Hypoxia in a Murine Model of Breast Cancer

Current noninvasive intravital imaging methods to map tumor hypoxia lack high spatial and temporal resolution, hindering accurate assessment of dynamic oxygen behavior. In this study, the authors utilized volumetric multispectral optoacoustic tomography (vMSOT), a label-free method that generates real-time, three-dimensional images in biological tissues, to characterize acute and cyclic hypoxia in a murine model of breast cancer. The authors could segment the murine tumors into three distinct subregions – the tumor rim, hypoxic core, and normoxic core – and could map their individual responses to oxygen stress. These results suggest that vMSOT could be a valuable tool to advance the imaging of cancer and help inform clinical decisions on therapeutic interventions. This article was featured on the cover of this issue.