Apo2L/TRAIL is a member of the tumor necrosis factor (TNF) family of cytokines that induces death of cancer cells but not normal cells. Its potent apoptotic activity is mediated through its cell surface death domain-containing receptors, DR4 and DR5. Apo2L/TRAIL interacts also with 3 "decoy" receptors that do not induce apoptosis, DcR1, DcR2, which lack functional death domains, and osteoprotegerin (OPG). The aim of our study was to investigate the cytotoxic activity

A prospective, randomized controlled study was performed to compare skin staplers for closure of skin following hip surgery. Patients were randomized to have their skin closed with either continuous subcuticular non‐absorbable polypropylene ‘prolene’ suture (33 patients) or metal skin staples (Autosuture ‘Premium’ or Davis and Geck ‘Oppose’; 33 patients). All patients received prophylactic cephalosporin (Cephalothin) in pre‐ and postoperative antibiotic therapy. The wounds were examined daily and the presence of discharge, wound dehiscence and infection were noted. Any discharge at 7 days was swabbed for microbiological examination. The final cosmetic appearance was assessed at 8–12 weeks postoperatively. Scar length and width were measured and the presence of cross‐hatching noted. Wound dehiscence occurred in 1 patient (closed with staples). Wound infection developed in 2 patients at a rate of 3% (1 patient from each group). At final review (8–12 weeks postop.), the scar produced by subcuticular prolene was narrower than that produced by the skin stapler (P < 0.05). There was no significant difference in scar width between a wound which had staples removed at 10 days post operation and one where the staples were removed at 14 days. Staple insertion sites were more obvious in scars that had had the staples removed at the later time (P < 0.05).

The Toronto Extremity Salvage Score (TESS) is widely used for the functional assessment of patients following surgery for musculoskeletal tumours. The aim of this study was to determine if there are gender and/or age-specific changes, unrelated to surgery, that may influence this score and the appropriateness of the questions. The TESS for lower limb was carried out in two different countries to see if there was variation between them. There were no statistically significant differences between the scores obtained between the respondents from Australia or Britain either in total or between the corresponding age groups. There were statistically significant differences in the TESS obtained between age groups with a lower score at older age groups but there was no difference between the sexes. Patients in the age group 70+ were more likely to record activities as “not applicable” and also have a lower score. This study has shown that age is the major factor in determining the TESS in both an Australian and British populations of otherwise healthy people. As there were no differences between the two populations, it supports the TESS as an international scoring system. There may be also an argument for age-specific questions.

This new technique has shown good early clinical and radiological responses and a low complication rate in a consecutive group of patients with ABC.

Background Metastatic disease commonly affects the proximal femur and occasionally the acetabulum. Surgical options include the use of a protrusio cage with a THA. However, the complications and survivorship of these cages for this indication is unknown. Questions/purposes The purpose was to report the restoration of function, complications and implant survival. Methods The medical records of 29 patients undergoing insertion of a protrusio cage for metastatic pelvic disease were reviewed. Complications were recorded. The most common diagnosis was metastatic breast cancer. During the review process, all but 10 of the 29 patients died 1-73 months after surgery. The median length of survival was 12 months (range, 3 days-100 months) after the procedure; 11 patients were alive at last followup at a median of 16 months (range, 1-100 months).

No abstract

Nutlin-3a is a small-molecule antagonist of p53/MDM2 that is being explored as a treatment for sarcoma. In this study, we examined the molecular mechanisms underlying the sensitivity of sarcomas to Nutlin-3a. In an ex vivo tissue explant system, we found that TP53 pathway alterations (TP53 status, MDM2/MDM4 genomic amplification/mRNA overexpression, MDM2 SNP309, and TP53 SNP72) did not confer apoptotic or cytostatic responses in sarcoma tissue biopsies (n ¼ 24). Unexpectedly, MDM2 status did not predict Nutlin-3a sensitivity. RNA sequencing revealed that the global transcriptomic profiles of these sarcomas provided a more robust prediction of apoptotic responses to Nutlin-3a. Expression profiling revealed a subset of TP53 target genes that were transactivated specifically in sarcomas that were highly sensitive to Nutlin-3a. Of these target genes, the GADD45A promoter region was shown to be hypermethylated in 82% of wild-type TP53 sarcomas that did not respond to Nutlin-3a, thereby providing mechanistic insight into the innate ability of sarcomas to resist apoptotic death following Nutlin-3a treatment. Collectively, our findings argue that the existing benchmark biomarker for MDM2 antagonist efficacy (MDM2 amplification) should not be used to predict outcome but rather global gene expression profiles and epigenetic status of sarcomas dictate their sensitivity to p53/MDM2 antagonists. Cancer Res; 74(3); 921-31. Ó2013 AACR.

BACKGROUND The molecular mechanisms underlying malignancy of osteosarcoma are unknown. It has been reported that eph receptor protein tyrosine kinases and their ligands, ephrins, are associated with increased tumorigenicity in patients with breast carcinoma and melanoma. The expression and role of eph/ephrins in human osteosarcoma has not yet been characterized. METHODS Ephrin‐A1, ephrin‐A3, ephrin‐A4, ephrin‐A5, ephrin‐B1, ephrin‐B2, and ephrin‐B3 mRNA expression was examined by reverse transcription polymerase chain reaction analysis in nine specimens of human osteosarcoma tissue and five human osteosarcoma cell lines. Ephrin‐B1 protein expression was detected immunohistochemically in human osteosarcoma tissue. Clinicopathologic correlation was made between the osteosarcoma specimens and their ephrin expression profiles. RESULTS Normal bone specimens, osteosarcoma tissue specimens, and osteosarcoma cell lines expressed a distinct mRNA profile of ephrin‐A1, ephrin‐A4, and ephrin‐B2. A second mRNA profile that included ephrin‐A3, ephrin‐A5, and ephrin‐B1 was expressed by a subset of tumors. The expression of ephrin‐B1 was correlated with a poorer clinical prognosis. Ephrin‐B1 protein was expressed by osteosarcoma cells and blood vessels. CONCLUSIONS The results of this study suggest that ephrin‐B1 expressed by osteosarcoma may be a poor prognostic marker through increased tumorigenicity. Cancer 2002;95:862–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10749