By virtue of their accumulated genetic alterations, tumor cells may acquire vulnerabilities that create opportunities for therapeutic intervention. We have devised a massively parallel strategy for screening short hairpin RNA (shRNA) collections for stable loss-of-function phenotypes. We assayed from 6000 to 20,000 shRNAs simultaneously to identify genes important for the proliferation and survival of five cell lines derived from human mammary tissue. Lethal shRNAs common to these cell lines targeted many known cell-cycle regulatory networks. Cell line–specific sensitivities to suppression of protein complexes and biological pathways also emerged, and these could be validated by RNA interference (RNAi) and pharmacologically. These studies establish a practical platform for genome-scale screening of complex phenotypes in mammalian cells and demonstrate that RNAi can be used to expose genotype-specific sensitivities.

Purpose

While the strength of a tendon repair is clearly important, the friction of the repair is also a relevant consideration. The purpose of this study was to characterize the frictional coefficient, gliding resistance and breaking strength of suture materials and a suture construct commonly used for flexor tendon repair.

Methods

We measured the friction coefficients of 3-0 braided nylon enclosed in a smooth nylon outer shell (Supramid, S. Jackson, Alexandria, VA), 3-0 braided polyester coated with polybutilate (Ethibond, Ethicon, Somerville, NJ), and a 3-0 braided polyester/monofilament polyethylene composite (FiberWire, Arthrex, Naples, FL) sutures. We also measured the gliding resistance, linear breaking strength and resistance to gapping of zone 2 modified Pennington tendon repairs with the two lowest friction sutures in 20 human cadaveric flexor digitorum profundus (FDP) tendons.

Results

The braided polyester/monofilament polyethylene composite had a significantly lower friction coefficient (0.054) than either the coated polyester (0.076) or nylon (0.130) sutures (p<0.001). The gliding resistances of the repaired tendons with braided/monofilament polyethylene composite suture and coated, braided polyester were similar (p> 0.05). The strength of the two repairs, force to produce a 2mm gap, and resistance to gap formation than coated, braided polyester repairs were also not significantly different.

Conclusion

Braided polyester composite is a low friction suture material. However, when this suture was used for tendon repair with a locking suture technique, it did not show a significant effect on the gliding resistance and repair strength compared with the same repair using coated polyester suture.

Summary

Identification of bona fide tumor suppressors is often challenging because of the large number of alterations present in most human cancers. To evaluate candidates present within regions recurrently deleted in human cancers we coupled high-resolution genomic analysis with a two-stage genetic study using RNA interference (RNAi). We found that Cyfip1, a subunit of the WAVE complex, which regulates cytoskeletal dynamics, is commonly deleted in human epithelial cancers. Reduced expression of Cyfip1 is commonly observed during invasion of epithelial tumors and it associated with poor prognosis in same tumor types. Silencing of Cyfip1 disturbed normal epithelial morphogenesis in vitro and cooperated with oncogenic Ras to produce invasive carcinomas in vivo. Mechanistically, we have linked alterations in WAVE-regulated actin dynamics with impaired cell-cell adhesion and cell-ECM interactions. Thus, we propose Cyfip1 as an invasion suppressor gene.