Publications

PURPOSE

Little is known about the prevalence of combined anxiety and depressive symptoms (CADS) in breast cancer patients. Purpose was to evaluate for differences in demographic and clinical characteristics and quality of life (QOL) prior to breast cancer surgery among women classified into one of four distinct anxiety and/or depressive symptom groups.

METHODS

A total of 335 patients completed measures of anxiety and depressive symptoms and QOL prior to and for 6 months following breast cancer surgery. Growth Mixture Modelling (GMM) was used to identify subgroups of women with distinct trajectories of anxiety and depressive symptoms. These results were used to create four distinct anxiety and/or depressive symptom groups. Differences in demographic, clinical, and symptom characteristics, among these groups were evaluated using analyses of variance and Chi square analyses.

RESULTS

A total of 44.5% of patients were categorized with CADS. Women with CADS were younger, non-white, had lower performance status, received neoadjuvant or adjuvant chemotherapy, had greater difficulty dealing with their disease and treatment, and reported less support from others to meet their needs. These women had lower physical, psychological, social well-being, and total QOL scores. Higher levels of anxiety with or without subsyndromal depressive symptoms were associated with increased fears of recurrence, hopelessness, uncertainty, loss of control, and a decrease in life satisfaction.

CONCLUSIONS

Findings suggest that CADS occurs in a high percentage of women following breast cancer surgery and results in a poorer QOL. Assessments of anxiety and depressive symptoms are warranted prior to surgery for breast cancer.

BACKGROUND

The mammalian target of rapamycin (mTOR) pathway is essential for tumor development, yet mTOR inhibitors have yielded modest results. This phase 1 study investigated the mTORC1/mTORC2 inhibitor CC-223 in patients with advanced cancer.

METHODS

Patients with advanced solid tumors or multiple myeloma received an initial dose of 7.5-60 mg of CC-223, followed by oral daily dosing in 28-day cycles until disease progression. The primary objective was to determine the safety, tolerability, nontolerated dosage, maximum tolerated dosage (MTD), and preliminary pharmacokinetic profile. Secondary objectives were to evaluate pharmacodynamic effects and to describe preliminary efficacy.

RESULTS

Twenty-eight patients were enrolled and received ≥1 dose of CC-223. The most common treatment-related grade 3 adverse events were hyperglycemia, fatigue, and rash. Four patients had dose-limiting toxicities, including hyperglycemia, rash, fatigue, and mucositis. Therefore, 45 mg/d was determined to be the MTD. The pharmacokinetics of CC-223 demonstrated a mean terminal half-life ranging from 4.86 to 5.64 hours and maximum observed plasma concentration ranging from 269 to 480 ng/mL in patients who received CC-223 ≥45 mg/d. Phosphorylation of mTORC1/mTORC2 pathway biomarkers in blood cells was inhibited by CC-223 ≥30 mg/d with an exposure-response relationship. Best responses included 1 partial response (breast cancer; response duration 220 days; 30-mg/d cohort), stable disease (8 patients across ≥15 mg/d cohorts; response duration range, 36-168 days), and progressive disease (12 patients). The disease control rate was 32%.

CONCLUSIONS

CC-223 was tolerable, with manageable toxicities. Preliminary antitumor activity, including tumor regression, and evidence of mTORC1/mTORC2 pathway inhibition were observed.

Dopaminergic therapies have been a mainstay of restless legs treatment and are endorsed as first-line therapies by multiple professional societies. This article summarizes the differences and similarities among the dopamine agonists with attention to pharmacology, efficacy, side effects, and dosing.

Tissue morphogenesis and organ formation are the consequences of biochemical and biophysical cues that lead to cellular spatial patterning in development. To model such events in vitro, we use PEG-patterned substrates to geometrically confine human pluripotent stem cell colonies and spatially present mechanical stress. Modulation of the WNT/β-catenin pathway promotes spatial patterning via geometric confinement of the cell condensation process during epithelial-mesenchymal transition, forcing cells at the perimeter to express an OCT4+ annulus, which is coincident with a region of higher cell density and E-cadherin expression. The biochemical and biophysical cues synergistically induce self-organizing lineage specification and creation of a beating human cardiac microchamber confined by the pattern geometry. These highly defined human cardiac microchambers can be used to study aspects of embryonic spatial patterning, early cardiac development and drug-induced developmental toxicity.