Complete Femoral Nerve Resection with Soft Tissue Sarcoma: Functional Outcomes

Background  

The functional consequences of resecting the femoral nerve in conjunction with soft tissue sarcoma management are not well described. In comparison, sciatic nerve involvement by sarcoma was once considered an indication for amputation, but sciatic resection is now commonly performed as part of a limb-salvage approach. We compared functional outcomes following resection of either the femoral or sciatic nerve in patients with soft tissue sarcoma. We also compared both groups with patients with large thigh sarcomas without nerve involvement.     

Surplus embryos in Switzerland in 2003: legislation and availability of human embryos for research

Legislation influences the availability of embryos for research. The law in Switzerland, and in some other European countries, is restrictive concerning medically assisted reproduction and stem cell research. Swiss law prohibits the creation of embryos for research purposes. It permits the derivation of human embryonic stem cells for research from surplus embryos but prohibits research with intact surplus embryos and embryo donation to other couples. Swiss law defines all embryos generated during a reproductive cycle and not used for reproduction as surplus embryos. The aim of this study was to evaluate the surplus embryos generated in Switzerland in 2003. A detailed questionnaire was sent to all registered IVF units in Switzerland (n = 22). 11727 embryos were generated during 2003. Of these, 93.5% were transferred into the uterus and 0.4% were cryopreserved. The remaining 6.1% (n = 711) became surplus. Of these, 2.7% were transferred intravaginally and the rest discarded due to poor quality (1.6%), development arrest (1.5%), renunciation by the couple (0.2%) or for other reasons (0.1%). The number of surplus embryos in Switzerland in 2003 was evaluated. Most surplus embryos became so during a therapeutic cycle. The restrictive legal regulation decreases the availability of human embryos for research.     

Hedgehog and Notch signaling regulate self-renewal of undifferentiated pleomorphic sarcomas

Like many solid tumors, sarcomas are heterogeneous and include a small fraction of the so-called side population (SP) cells with stem-like tumor-initiating potential. Here, we report that SP cells from a soft tissue tumor of enigmatic origin termed undifferentiated pleomorphic sarcoma (also known as malignant fibrous histiocytoma or MFH sarcoma) display activation of both the Hedgehog and Notch pathways. Blockade to these pathways in murine xenograft models, this human cancer decreased the proportion of SP cells present and suppressed tumor self-renewal, as illustrated by the striking inability of xenograft tumors subjected to pathway blockade to be serially transplanted to new hosts. In contrast, conventional chemotherapies increased the proportion of SP cells present in tumor xenografts and did not affect their ability to be serially transplanted. SP cells from these tumors displayed an unexpectedly high proliferation rate which was selectively inhibited by Hedgehog and Notch blockade compared with conventional chemotherapies. Together, our findings deepen the concept that Hedgehog and Notch signaling are fundamental drivers of tumor self-renewal, acting in a small population of tumor-initiating cells present in tumors. Furthermore, our results suggest not only novel treatment strategies for deadly recurrent unresectable forms of this soft tumor subtype, but also potential insights into its etiology which has been historically controversial.     

Interface effects on mechanical properties of particle-reinforced composites.

OBJECTIVES: Effective bonding between the filler and matrix components typically improves the mechanical properties of polymer composites containing inorganic fillers. The aim of this study was to test the hypothesis that composite flexural modulus, flexure strength, and toughness are directly proportional to filler-matrix interfacial shear strength. METHODS: The resin matrix component of the experimental composite consisted of a 60:40 blend of BisGMA:TEGDMA. Two levels of photoinitiator components were used: 0.15, and 0.5%. Raman spectroscopy was used to determine degree of cure, and thermogravimetry (TGA) was used to quantify the degree of silane, rubber, or polymer attachment to silica and glass particles. Filler-matrix interfacial shear strengths were measured using a microbond test. Composites containing glass particles with various surface treatments were prepared and the modulus, flexure strength, and fracture toughness of these materials obtained using standard methods. Mechanical properties were measured on dry and soaked specimens. RESULTS: The interfacial strength was greatest for the 5% MPS treated silica, and it increased for polymers prepared with 0.5% initiator compared with 0.15% initiator concentrations. For the mechanical properties measured, the authors found that: (1) the flexural modulus was independent of the type of filler surface treatment, though flexural strength and toughness were highest for the silanated glass; (2) rubber at the interface, whether bonded to the filler and matrix or not, did not improve toughness; (3) less grafting of resin to silanated filler particles was observed when the initiator concentration decreased. SIGNIFICANCE: These findings suggest that increasing the strength of the bond between filler and matrix will not result in improvements in the mechanical properties of particulate-reinforced composites in contrast to fiber-reinforced composites. Also, contraction stresses in the 0.5 vs 0.15% initiator concentration composites may be responsible for increases in interfacial shear strengths, moduli, and flexural strengths.     

Inhibition of P53-mediated cell cycle control as the determinant in dedifferentiated liposarcomas development

Liposarcomas are a heterogeneous group of sarcomas, including well-differentiated and dedifferentiated liposarcoma, myxoid/round cell liposarcoma, and pleomorphic liposarcoma. Complete surgical resection is the key of treatment. Radiotherapy, based on the tumor grade and the vicinity of critical structures with the tumor, can be used to prevent local recurrence. The group of dedifferentiated liposarcomas (DDLS) is poorly sensitive to adjuvant chemotherapy. Improved understanding of the genetic aberrations that lead to liposarcoma initiation is necessary for the development of targeted therapies to improve tumor control and survival. DDLS share genetic abnormalities with other groups, exhibiting high-level amplifications of chromosome 12, including the MDM2 and CDK4 genes, and harbor additional amplifications of chromosomes 6 and 1. Novel therapies targeted at the gene products of chromosome 12 are currently considered in clinical trials. Our work consisted in a genomic characterization of DDLS to draw up a complete picture of alterations, including genomic signatures, tumor mutation burden, gene mutations, copy number variations, translocations, gene fusions and methylation modifications. Analysis of translocations helped to understand the mechanisms underlying the amplification processes. Combination of mutations and loss of heterozygosity or homozygous deletions were detected and led to inactivate tumor suppressor genes (TSG). In contrast, methylation anomalies seemed not linked to any particular genomic profile. All identified anomalies, whether amplifications and/or TSG inactivation, involve genes playing a role in p53 regulation, that appears to be the epicenter of the initiation process in DDLS tumorigenesis, as is also known to be responsible for Li-Fraumeni syndrome, a family cancer syndrome highly predisposing to sarcomas.