Stromal Senescence following Treatment with the CDK4/6 Inhibitor Palbociclib Alters the Lung Metastatic Niche and Increases Metastasis of Drug-Resistant Mammary Cancer Cells.

Background: CDK4/6 inhibitors (CDKi) have improved disease control in hormone-receptor-positive, HER2-negative metastatic breast cancer, but most patients develop progressive disease.

Methods: We asked whether host stromal senescence after CDK4/6 inhibition affects metastatic seeding and growth of CDKi-resistant mammary cancer cells by using the p16-INK-ATTAC mouse model of inducible senolysis.

Results: Palbociclib pretreatment of naïve mice increased lung seeding of CDKi-resistant syngeneic mammary cancer cells, and this effect was reversed by depletion of host senescent cells.

Tumor Dormancy and Slow-Cycling Cancer Cells.

Cancer cell heterogeneity is a universal feature of human tumors and represents a significant barrier to the efficacy and duration of anticancer therapies, especially targeted therapeutics. Among the heterogeneous cancer cell populations is a subpopulation of relatively quiescent cancer cells, which are in the G0/G1 cell-cycle phase and refractory to anti-mitotic drugs that target proliferative cells. These slow-cycling cells (SCCs) preexist in untreated tumors and frequently become enriched in treatment-failed tumors, raising the possibility that these cells may mediate therapy resistance and tumor relapse.

Normobaric Hypoxia Effects on Balance Measured by Computerized Dynamic Posturography.

Unlabelled: Wagner, Dale R., Skyler Saunders, Brady Robertson, and John E. Davis.

Cognitive and psychomotor responses to high-altitude exposure in sea level and high-altitude residents of Ecuador.

Background: High-altitude inhabitants have cardiovascular and respiratory adaptations that are advantageous for high-altitude living, but they may have impaired cognitive function. This study evaluated the influence of altitude of residence on cognitive and psychomotor function upon acute exposure to very high altitude.

Findings: Ecuadorians (31 residing at 0-1,500 m [LOW], 78 from 1,501-3,000 m [MOD], and 23 living >3,000 m [HIGH]) were tested upon their arrival to a hut at 4,860 m on Mount Chimborazo.

Cerebral autoregulation index at high altitude assessed by thigh-cuff and transfer function analysis techniques.

New Findings: What is the central question of this study? Whether cerebral autoregulation (CA) is impaired at high altitude and associated with acute mountain sickness remains controversial. We sought to compare two of the most common methods to assess dynamic CA in subjects who ascended to 3424 m and acclimatized. What is the main finding and its importance? We found that CA was reduced at 3424 m when assessed by the classic thigh-cuff inflation-deflation technique, but not when evaluated by transfer function analysis.

Orthostatic responses at 4860 m in low, moderate, and high altitude residents.

This study evaluated the influence of altitude of residence on orthostatic responses when exposed to high altitude. Data collection took place at the Carrel hut (4860 m) on Chimborazo in Ecuador. After being transported to the hut by vehicle, 69 people volunteered for the study.