Andrew M. Namen

Magnitude of Peroxisome Proliferator-Activated Receptor-γ Activation is Associated With Important and Seemingly Opposite Biological Responses in Breast Cancer Cells

Background The nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) has become a potential target for the prevention and treatment of breast cancer. However, recent in vitro and in vivo studies have raised the question of whether activation of PPARγ leads to the promotion or reduction of tumor formation. Studies using several cancer cell lines, animal models, and a variety of PPARγ agonists have shown discordant results, including changes in cellular proliferation, differentiation, and apoptosis of cancer cells and tumors. Methods We studied the effects of low-, moderate-, and high-dose treatment of the PPARγ ligands 15-deoxy-Δ12,14 prostaglandin J2 (15dPGJ2) and troglitazone (TGZ) on parameters of cell growth, differentiation, and apoptosis in the epithelial breast cancer cell line MDA-MB-231. Results The biologic effects of these compounds depend largely on ligand concentration and the degree of PPARγ activation. For example, low concentrations of 15dPGJ2 (<2.5 μM) and TGZ (<5 μM) increased cellular proliferation, but concentrations of 15dPGJ2 >10 μM and of TGZ at 100 μM blocked cell growth. TGZ (100 μM) slowed cell cycle progression, and 15dPGJ2 (10 μM) caused an S-phase arrest in the cell cycle and induced morphological characteristics consistent with apoptosis. Expression of CD36, a marker of differentiation in these cells, was induced by 2.5 μM 15dPGJ2 or 5 to 100 μM TGZ. However, higher concentrations of 15dPGJ2 did not alter CD36 expression. Transcriptional activation studies demonstrated that 15dPGJ2 is a more potent PPARγ ligand than TGZ. Regardless of the ligand used, though, low transcriptional activation correlated with an increased cellular proliferation, whereas higher levels of activation correlated with cell cycle arrest and apoptosis. Conclusions PPARγ activation induces several important and seemingly opposite changes in neoplastic cells, depending on the magnitude of PPARγ activation. These data may explain, at least in part, some of the discordant results previously reported.

Physicians Report Sleep Apnea Infrequently in Older and Older Vulnerable Adults

To determine how often outpatient physician visits detect sleep apnea (SA) in older persons in the United States.

Pulmonary Infiltrates After Intravesical Bacille Calmette-Guerin: Two Cases and Review of the Literature

Bacille Calmette-Guerin (BCG) is used for intravesical immunotherapy in the treatment of transitional cell carcinoma of the bladder. Patients treated with intravesical BCG frequently experience local reactions to instillation; however, some patients have systemic reactions to BCG. It is sometimes unclear whether this systemic response represents a hypersensitivity reaction or a disseminated infection. We present 2 patients with micronodular pulmonary infiltrates and systemic symptoms of fevers, chills, and night sweats after multiple instillations of intravesical BCG. In the first case, the patient failed to respond to antimycobacterial therapy but rapidly improved with the addition of corticosteroids. In the second case, the patient refused therapy, and symptoms and radiographic infiltrates resolved. Responses to steroid therapy and spontaneous recovery in suspected BCG pneumonitis suggests a hypersensitivity reaction; however, the exact pathobiology remains uncertain and mycobacterial infection often cannot be discounted. Treatment of patients with pulmonary complications after intravesical BCG may typically involve both antimycobacterial drugs and/or corticosteroids.