Osteosarcoma

Human mesenchymal stem/stromal cells (hMSCs) have been shown to support breast cancer cell proliferation and metastasis, partly through their secretome. hMSCs have a remarkable ability to survive for long periods under stress, and their secretome is tumor supportive. In this study, we have characterized the cargo of extracellular vesicular (EV) fraction (that is in the size range of 40-150nm) of serum deprived hMSCs (SD-MSCs). Next Generation Sequencing assays were used to identify small RNA secreted in the EVs, which indicated presence of tumor supportive miRNA. Further assays demonstrated the role of miRNA-21 and 34a as tumor supportive miRNAs. Next, proteomic assays revealed the presence of ≈150 different proteins, most of which are known tumor supportive factors such as PDGFR-β, TIMP-1, and TIMP-2. Lipidomic assays verified presence of bioactive lipids such as sphingomyelin. Furthermore, metabolite assays identified the presence of lactic acid and glutamic acid in EVs. The co-injection xenograft assays using MCF-7 breast cancer cells demonstrated the tumor supportive function of these EVs. To our knowledge this is the first comprehensive -omics based study that characterized the complex cargo of extracellular vesicles secreted by hMSCs and their role in supporting breast cancers.

Background Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment.

Radiographs of 33 patients who had an expandable prosthesis inserted after tumor resection in the distal femur were evaluated. We hypothesized that, when a sleeve was present, there was greater stem migration and cortical reaction. The thickness of medial and lateral cortices of the tibia was measured at 6 months and on the last follow-up radiograph. The distance from the edge of the prosthesis to the cortical edge was also compared. When a sleeve was present, there was greater stem migration (P b .001) and a greater increase in lateral cortical thickness (P b .001). There was a higher revision rate when a sleeve was used, but this was not statistically significant. There was no difference in function according to the Toronto Extremity Salvage Score (TESS) between the 2 groups. This is the first study to demonstrate that the presence of a polyethylene sleeve is associated with a tendency for the tibial prosthesis to migrate laterally and cause a greater sclerotic reaction.

Radiation therapy is frequently used method in treatment of the head and neck malignancies. Osteosarcoma is a rare complication of radiation therapy and usually occurs after a long latent period. We report the case of 75-year-old female with osteosarcoma of the mastoid process. Twelve years before presentation she received radiation therapy after total parotidectomy and radical neck dissection in treatment of mucoepidermoid carcinoma of the parotid gland. Diagnostic procedures included contrast-enhanced CT and MRI of the head and neck and HRCT of the temporal bone. The final diagnosis of the low grade osteosarcoma was confirmed by biopsy. Diagnostic criteria were fulfilled and the lesion was classified as a radiation induced osteosarcoma.

The purpose of the present investigation was to study the effect of delay in fixation on the mitotic activity in tumour tissue. A human osteogenic sarcoma, especially suitable for counting of mitoses, grown in athymic nude mice, was fixed with varying delay and the mitotic, prophase, metaphase and ana-telophase indices were determined. An almost exponential decline of the mitotic index was observed with a reduction to 49.4% and 15.0% after respectively 60 and 180 minutes. The proportional incidence of prophases, metaphases and ana-telophases changed so that a relative accummulation of advanced phases occured during the 180 minutes of observation. It is concluded that delay in fixation of a magnitude, which is not uncommon in routine surgical pathology, may allow the majority of mitoses to terminate, resulting in unreliable assessments of mitotic activity.

NDOUR O., NGOM G., FAYE FALL A., FALL MB., DIOUF C., FALL I., NDOYE M RESUME L'objectif de ce travail était de rapporter les aspects épidémiologiques, diagnostiques et thérapeutiques du tératome sacro-coccygien à Dakar. Il s'agissait d'une étude rétrospective portant sur 11 dossiers colligés entre juin 1995 et juin 2005. Les paramètres étudiés étaient l'âge, le sexe, les motifs de consultation, les signes cliniques et paracliniques, les données du traitement chirurgical, la durée d'hospitalisation, les suites opératoires et l'examen anatomopathologique de la pièce opératoire. Apres recueil des données, les patients ont été repartis selon la classification d'Altmann. L'âge moyen de nos patients était de 10 mois avec des extrêmes de 2 jours et 4 ans. Une nette prédominance féminine a été notée. La masse tumorale était le principal motif de consultation. L'examen clinique avait retrouvé 11 tératomes type I selon la classification d'Altmann. La radiographie standard réalisée chez 9 patients montrait dans 6 cas des calcifications au sein de la densité tumorale. L'échographie faite chez 5 patients montrait une masse hétérogène rétrosacrée. La tomodensitométrie réalisée chez 3 patients montrait une masse hétérogène appendue au sacrum. Tous les patients ont pu bénéficier d'une résection monobloc emportant la pointe du coccyx. La durée d'hospitalisation moyenne était d'un mois. Chez 6 patients les suites opératoires ont été simples. Cinq cas de suppuration ont été notés et ont bien évolué après soins locaux. L'examen anatomopathologique de la pièce opératoire révélait dans tous les cas un tératome mature. Le tératome sacro-coccygien est une anomalie congénitale rare dont le diagnostic est souvent fait tardivement dans notre contexte. Son traitement est essentiellement chirurgical et donne de bons résultats s'il est réalisé précocement. Cependant un suivi à long terme est nécessaire du fait du risque de transformation maligne. Nous recommandons le dosage de l'alpha foeto-protéine dans la surveillance de ces tératomes.

Osteosarcoma cells are recognized by abnormal function that causes a primary bone tumor. Osteosarcoma cells U 2 OS and SAOS-2 were analyzed for the expression of cell surface markers. High expression was quanti®ed for hyaloronidase receptor (CD-44) b moderate for integrins (CD-51 and -61), b and lower for selectins . High mitotic capacity were demonstrated by gene expression (measured by RT-PCR) and the protein level (measured by FACS) for cFOS, cMYC, and cJUN. The basic de®nition of osteosarcoma is excessive production of pathological osteoid. Expression of mRNA for matrix genes osteocalcin, osteonectin, and biglycan was studied. Osteocalcin and osteonectin were detected in RNA from primary cultured marrow stromal, trabecular bone cells, and osteosarcoma cell lines (U 2 OS, SAOS-2). mRNA for biglycan was detected only in primary cells and MG-63 cell line and was undetectable in RNA from U 2 OS, SAOS-2 osteosarcoma cell lines and by RNA extracted from bone biopsies of osteosarcoma patients. The absence of biglycan message observed in osteosarcoma samples provides evidence for the alterations in the extra cellular matrix which result with non-mineralized osteoid produced by the osteosarcoma cells.

Osteosarcoma accounts for most primary bone cancers in children and young adults. High-grade lesions are typically managed with a combination of chemotherapy and wide-margin surgical excision. Although this malignancy typically affects the metaphyseal region of long bones, it also can be seen in the axial skeleton. Of axial locations, tumors in the head and neck can be particularly troubling to treat. Segmental bone loss after resection of malignant mandibular tumors continues to present important challenges to the reconstructive surgeon. Recent advancements in 3-dimensional modeling have facilitated custom templates for patient-specific reconstructions. This report describes the case of a young woman with osteosarcoma of the mandible undergoing customized template composite facial reconstruction using a vascularized osteoseptocutaneous fibula flap. Ó

Aims & method: In this study, a microbial polyester, poly(3-hydroxybutyrate-co- 3-hydroxyvalerate) (PHBV), and its blends were electrospun into PHBV (10% w/v), PHBV (15% w/v), PHBV-PLLA (5% w/v), PHBV-PLGA (50:50) (15% w/v) and PHBV-P(L,DL)LA (5% w/v) fibrous scaffolds for tissue engineering. Results: Various processing parameters affected the morphology and the dimensions of beads formed on the fibers. Concentration was highly influential on fiber properties; as it increased from 5 to 15% (w/v), fiber diameter increased from 284 ± 133 nm to 2200 ± 716 nm. Increase in potential (from 20 to 50 kV) did not lead to the expected decrease in fiber diameter. The blends of PHBV with lactide-based polymers led to fibers with less beads and more uniform diameter. The surface porosities for PHBV10, PHBV15, PHBV-PLLA, PHBV-PLGA (50:50) and PHBV-P(L,DL)LA were 38.0 ± 3.8, 40.1 ± 8.5, 53.8 ± 4.2, 50.0 ± 4.2 and 30.8 ± 2.7%, respectively. In vitro studies using human osteosarcoma cells (Saos-2) revealed that the electrospun scaffolds promoted cell growth and penetration. Surface modification with oxygen plasma treatment slightly improved the improved the results in terms of cell number increase and significantly improved spreading of the cells. Conclusion: All scaffolds prepared by electrospinning have implied significant potential for use in further studies leading to bone tissue engineering applications. The PHBV-PLLA blend appeared to yield the best results regarding cell number increase, their attachment and spreading inside and on the scaffold.

Purpose: To assess clinical behavior, response to treatment, and factors affecting survival in maxillofacial osteosarcoma treated at a tertiary referral center. Patients and Methods: Ethics-approved retrospective review of clinical and pathological records was undertaken for 15 patients managed by the Royal Melbourne Hospital Head and Neck Oncology Tumor Stream. Results: Treatment was a combination of surgery and chemotherapy. Chemotherapy was given as adjuvant, neoadjuvant, or in combination. The overall 2-, 5-, and 15-year disease-free survival rates in this study were 92%, 74%, and 74%, respectively. Using Kaplan-Meier analysis with log rank tests, increasing T stage (P ϭ .01) and positive margins (P ϭ .003) were found to affect survival significantly. Neoadjuvant chemotherapy was not significantly associated with tumor necrosis or improved survival. Conclusions: Tumor size and adequacy of local control were found to be the most important predictors of outcome.

Despite advances in diagnostic imaging, the evolution of neoadjuvant chemotherapy and the refinements in limb-salvage surgery, the progression-free survival rate remains poor for patients with metastatic, recurrent or unresectable osteosarcoma. Different therapeutic strategies for these subgroups of patients have been employed to control disease and prolong survival. Treatment options are limited and controversial, including systemic and localized therapies. Surgical resection, whenever feasible, is still the standard treatment in advanced osteosarcoma. The role of chemotherapy is unclear while the use of radiotherapy, embolization and thermal ablation is increasing. New therapeutic experimental approaches and novel target therapies are needed to improve the outcome of these subgroups of patients.

Background: In osteosarcoma, the presence of tumor-infiltrating macrophages positively correlates with patient survival in contrast to the negative effect of tumor-associated macrophages in patients with other tumors. Liposome-encapsulated muramyl tripeptide (L-MTP-PE) has been introduced in the treatment of osteosarcoma patients, which may enhance the potential anti-tumor activity of macrophages. Direct anti-tumor activity of human macrophages against human osteosarcoma cells has not been described so far. Hence, we assessed osteosarcoma cell growth after co-culture with human macrophages.