Ras inhibition boosts galectin-7 at the expense of galectin-1 to sensitize cells to apoptosis.

Galectins are a family of β-galactoside-binding lectins that exert diverse extracellular and intracellular effects. Galectin-7 and galectin-1 show opposing effects on proliferation and survival in different cell types. Galectin-7 is a p53-induced gene and an enhancer of apoptosis, whereas galectin-1 induces tumorigenicity and resistance to apoptosis in several types of cancers.

Phenotypic reversion of invasive neurofibromin-deficient schwannoma by FTS: Ras inhibition reduces BMP4/Erk/Smad signaling.

Neurofibromin-deficient (Nf1(-/-)) malignant peripheral nerve sheath tumors (MPNST) are highly invasive, refractory to chemotherapy, and characterized by overactivated Ras. Ras activates mitogenic pathways and regulates morphogenic programs--such as those induced by bone morphogenetic proteins (BMP) and TGF-β. The role of such a cross-talk in determining the phenotype and transformation potential of MPNSTs is unknown.

Tumor cells secrete galectin-1 to enhance endothelial cell activity.

Tumor angiogenesis is a key event in cancer progression. Here, we report that tumors can stimulate tumor angiogenesis by secretion of galectin-1. Tumor growth and tumor angiogenesis of different tumor models are hampered in galectin-1-null (gal-1(-/-)) mice.

The tumor suppressor neurofibromin confers sensitivity to apoptosis by Ras-dependent and Ras-independent pathways.

Neurofibromatosis type 1 (NF1) is characterized by a high incidence of benign and malignant tumors attributed to loss of function of Nf1, which encodes neurofibromin, a tumor suppressor with Ras-GAP activity. Neurofibromin deficiency typically causes chronic activation of Ras, considered the major contributor to manifestation of NF1. Resistance to radio- and chemotherapy are typical of NF1-associated tumors, but the underlying mechanism is unknown.

The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for neurofibromatosis type 1.

Purpose: Farnesylthiosalicylic acid (FTS) is a Ras inhibitor that dislodges all active Ras isoforms from the membrane. We assessed the ability of FTS to reverse the transformed phenotype of neurofibromatosis type 1 (NF1)-associated tumor cell lines of malignant peripheral nerve sheath tumor (MPNST).

Experimental Design: nf1 mutations were genotyped, allelic losses were analyzed, and neurofibromin expression levels were determined in MPNST cell lines ST88-14, S265P21, and 90-8.

Spatiotemporal organization of Ras signaling: rasosomes and the galectin switch.

1. Ras signaling and oncogenesis depend on the dynamic interplay of Ras with distinctive plasma membrane (PM) microdomains and various intracellular compartments. Such interaction is dictated by individual elements in the carboxy-terminal domain of the Ras proteins, including a farnesyl isoprenoid group, sequences in the hypervariable region (hvr)-linker, and palmitoyl groups in H/N-Ras isoforms.

Golgi localization determinants in ArfGAP1 and in new tissue-specific ArfGAP1 isoforms.

The Arf1-directed GTPase-activating protein ArfGAP1 is a Golgi-localized protein that controls the dynamics of the COPI coat of carriers that mediate transport in the endoplasmic reticulum-Golgi shuttle. Previously the interaction of ArfGAP1 with the Golgi was allocated to a portion of the non-catalytic, carboxyl part of the protein, but the mechanism of this interaction has not been established. In this study we identify a short stretch in the non-catalytic part of ArfGAP1 (residues 204-214) in which several hydrophobic residues contribute to Golgi localization.

Digitizing and signal averaging of left ventricular pressure signals using a dedicated radionuclide imaging system.

A method for obtaining left ventricular (LV) volume curves, synchronized with average LV pressure (LVP) curves for calculation of LV contractility, is described. Multiple gated blood pool imaging was performed to calculate average LV volume curves. Simultaneously with this acquisition, LVPs and aortic pressures were measured by indwelling catheters and recorded on an FM tape recorder.