Differential expression of mTOR related molecules in the placenta from gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia patients.

The mechanistic target of rapamycin (mTOR) pathway is involved in the function and growth of the placenta during pregnancy. The mTOR pathway responds to nutrient availability and growth factors that regulate protein expression and cell growth. Disrupted mTOR signaling is associated with the development of several obstetric complications. The purpose of this study was to identify the differential placental expression of various mTOR-associated proteins in the placenta during normal gestation (Control), gestational diabetes mellitus (GDM), intrauterine growth restriction (IUGR) and preeclampsia (PE). Immunohistochemistry localized activated proteins (phospho; p) mTOR, pp70, p4EBP1, pAKT and pERK. Real-time PCR array was performed to show differing placental expression of additional mTOR-associated genes. Western blot was performed for pAMPK protein. We observed: 1) increased pmTOR during GDM and decreased pmTOR during IUGR and PE, 2) increased pp70 during IUGR and decreased pp70 during GDM and PE, 3) increased p4EBP1 during GDM, IUGR, and PE, 4) increased pAKT during GDM, 5) increased pERK during IUGR, 6) differential placental expression of mTOR pathway associated genes and increased pAMPK during GDM and PE. We conclude that regulation of the mTOR pathway is uniquely involved in the development of these obstetric complications. Insights into this pathway may provide avenues that if modify may help alleviate these diseases.

The transformation of the nuclear nanoarchitecture in human field carcinogenesis.

Morphological alterations of the nuclear texture are a hallmark of carcinogenesis. At later stages of disease, these changes are well characterized and detectable by light microscopy. Evidence suggests that similar albeit nanoscopic alterations develop at the predysplastic stages of carcinogenesis. Using the novel optical technique partial wave spectroscopic microscopy, we identified profound changes in the nanoscale chromatin topology in microscopically normal tissue as a common event in the field carcinogenesis of many cancers. In particular, higher-order chromatin structure at supranucleosomal length scales (20-200 nm) becomes exceedingly heterogeneous, a measure we quantify using the disorder strength (Ld ) of the spatial arrangement of chromatin density. Here, we review partial wave spectroscopic nanocytology clinical studies and the technology's promise as an early cancer screening technology.