Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma.

Pancreatic intraepithelial neoplasia is a pre-malignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance. The genomic alterations that commonly occur in pancreatic cancer include activation of KRAS2 and inactivation of p53 and SMAD4 (refs 2-4). So far, however, it has been challenging to target these pathways therapeutically; thus the search for other key mediators of pancreatic cancer growth remains an important endeavour.

Role of connexins in metastatic breast cancer and melanoma brain colonization.

Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain, specifically in close contact with the existing brain vasculature.

KRas induces a Src/PEAK1/ErbB2 kinase amplification loop that drives metastatic growth and therapy resistance in pancreatic cancer.

Early biomarkers and effective therapeutic strategies are desperately needed to treat pancreatic ductal adenocarcinoma (PDAC), which has a dismal 5-year patient survival rate. Here, we report that the novel tyrosine kinase PEAK1 is upregulated in human malignancies, including human PDACs and pancreatic intraepithelial neoplasia (PanIN). Oncogenic KRas induced a PEAK1-dependent kinase amplification loop between Src, PEAK1, and ErbB2 to drive PDAC tumor growth and metastasis in vivo.

Generalized megaviscera of lupus: refractory intestinal pseudo-obstruction, ureterohydronephrosis and megacholedochus.

Dilated dysfunction involving multiple visceral organs has been reported in patients with systemic lupus erythematosus (SLE). Chronic intestinal pseudo-obstruction (CIPO) resulting from intestinal smooth muscle damage has presented in conjunction with ureterohydronephrosis and, more rarely, biliary dilatation (megacholedochus). While the molecular pathogenesis is largely unknown, observed histopathologic features include widespread myositis, myocyte necrosis in the intestinal muscularis propria with subsequent atrophy and fibrosis, preserved myenteric innervations and little vasculitis.

C. elegans MOM-5/frizzled functions in MOM-2/Wnt-independent cell polarity and is localized asymmetrically prior to cell division.

C. elegans embryonic cells have a common anterior/posterior (a/p) polarity that is apparent in the localization of the transcription factor POP-1. The level of nuclear POP-1 remains high in the anterior daughters of dividing cells but is lowered in the posterior daughters.

Establishment of POP-1 asymmetry in early C. elegans embryos.

In Caenhorabtidis elegans embryos, the nuclei of sister cells that are born from anterior/posterior divisions show an invariant high/low asymmetry, respectively, in their level of the transcription factor POP-1. Previous studies have shown that POP-1 asymmetry between the daughters of an embryonic cell called EMS results in part from a Wnt-like signal provided by a neighboring cell, called P(2). We identify here additional signaling cells that play a role in POP-1 asymmetry for other early embryonic cells.