Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study.

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans.

Acentrosomal spindle organization renders cancer cells dependent on the kinesin HSET.

Centrosomes represent the major microtubule organizing centers (MTOCs) of animal somatic cells and orchestrate bipolar spindle assembly during mitotic cell division. In meiotic cells, the kinesin HSET compensates for the lack of centrosomes by focusing acentrosomal MTOCs into two spindle poles. By clustering multiple centrosomes into two spindle poles, HSET also mediates bipolar mitosis in cancer cells with supernumerary centrosomes.

Characterization of the mechanism of action of the pan class I PI3K inhibitor NVP-BKM120 across a broad range of concentrations.

The pan-phosphoinositide 3-kinase (PI3K) inhibitor BKM120 was found, at high concentrations, to cause cell death in various cellular systems, irrespective of their level of PI3K addiction. Transcriptional and biochemical profiling studies were used to identify the origin of these unexpected and apparently PI3K-independent effects. At 5- to 10-fold, the concentration needed to half-maximally inhibit PI3K signaling.

Control of centriole length by CPAP and CP110.

Centrioles function as the major components of centrosomes, which organize microtubule (MT) arrays in proliferating cells, and as basal bodies for primary cilia formation in quiescent cells. Centrioles and basal bodies are structurally similar, barrel-shaped organelles composed of MTs. In proliferating cells, two new centrioles, termed procentrioles, form during the S phase of the cell cycle in close proximity to the proximal ends of the two preexisting parental centrioles, often at a near-orthogonal angle.

Plk4-induced centriole biogenesis in human cells.

We show that overexpression of Polo-like kinase 4 (Plk4) in human cells induces centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole. This provided an opportunity for dissecting centriole assembly and characterizing assembly intermediates. Critical components were identified and ordered into an assembly pathway through siRNA and localized through immunoelectron microscopy.

Astrin is required for the maintenance of sister chromatid cohesion and centrosome integrity.

Faithful chromosome segregation in mitosis requires the formation of a bipolar mitotic spindle with stably attached chromosomes. Once all of the chromosomes are aligned, the connection between the sister chromatids is severed by the cysteine protease separase. Separase also promotes centriole disengagement at the end of mitosis.

Dictyostelium LIS1 is a centrosomal protein required for microtubule/cell cortex interactions, nucleus/centrosome linkage, and actin dynamics.

The widespread LIS1-proteins were originally identified as the target for sporadic mutations causing lissencephaly in humans. Dictyostelium LIS1 (DdLIS1) is a microtubule-associated protein exhibiting 53% identity to human LIS1. It colocalizes with dynein at isolated, microtubule-free centrosomes, suggesting that both are integral centrosomal components.