Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumour-infiltrating lymphocytes (TIL) of paediatric tumours obtained from 37 lesions of different histotype (12 osteosarcomas, 5 Wilms' tumours, 7 soft-tissue sarcomas, 5 neuroblastomas and 8 miscellaneous) were studied to establish their potential for therapy. Fresh isolated TIL were cultured for the first 2 weeks with low doses of interleukin-2 (IL-2) (20 Cetus U/ml) to select for "tumour-specific" lymphocytes potentially present in the neoplastic lesion, followed by culture with high doses of IL-2 (1000 Cetus U/ml) to achieve TIL expansion. TIL were grown with more than 10-fold expansion in only 9 cases (mean expansion: 58-fold, range 13.5-346). In 17 cases no viable cells were obtained. After 30 days of culture with IL-2 the proliferative ability of TIL declined sharply in the majority of cases and TIL became refractory to any further stimulus, including addition of IL-4, tumour necrosis factor alpha (TNF alpha) or interferon gamma, and activation with OKT3 in solid phase. In 20 out of 37 cases TIL were available for phenotypic and functional analysis. TIL after long-term culture were predominantly CD3+ but 2 cases of osteosarcoma showed a predominance of CD3+TcR gamma/delta cells. The CD4/CD8 ratio was more than 1 in 10 cases, without correlation with tumour histology, site of lesion or TIL growth. The number of CD16+ and CD25+ lymphocytes decreased progressively during culture, the latter concomitantly with a reduction of TIL growth rate. The lytic pattern of TIL against allogenic and autologous tumour (Auto-Tu) cells was variable, but specific lysis of Auto-Tu was seen in only one case (Wilms' tumour) after culture with TNF alpha and irradiated Auto-Tu cells. The immunohistochemical analysis of tumour lesions revealed a limited lymphocyte infiltrate, a low expression of histocompatibility leukocyte antigens (HLA) class I and of the adhesion molecules ICAM1, LFA3, and a significant production of transforming growth factor beta (TGF beta). These data indicate that TIL obtained from paediatric patients are difficult to expand at levels required for immunotherapy and lack a significant number of tumour-specific T lymphocytes. A low expression of immunomodulatory molecules on tumour cells or the production of suppressive factors may prevent activation and expansion of TIL in paediatric tumours.
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PMID:Phenotypic and functional analysis of lymphocytes infiltrating paediatric tumours, with a characterization of the tumour phenotype. 131 Dec 18

Absolute lymphocyte count (ALC) recovery rapidly occurring at 14 days after start of chemotherapy for osteosarcoma and Ewing sarcoma is a good prognostic factor. Conversely, lymphopenia is associated with significantly decreased sarcoma survival. Clearly, the immune system can contribute towards better survival from sarcoma. This chapter will describe treatment and host factors that influence immune function and how effective local control and systemic interventions of sarcoma therapy can cause inflammation and/or immune suppression but are currently the standard of care. Preclinical and clinical efforts to enhance immune function against sarcoma will be reviewed. Interventions to enhance immune function against sarcoma have included regional therapy (surgery, cryoablation, radiofrequency ablation, electroporation, and radiotherapy), cytokines, macrophage activators (mifamurtide), vaccines, natural killer (NK) cells, T cell receptor (TCR) and chimeric antigen receptor (CAR) T cells, and efforts to decrease inflammation. The latter is particularly important because of new knowledge about factors influencing expression of checkpoint inhibitory molecules, PD1 and CTLA-4, in the tumor microenvironment. Since these molecules can now be blocked using anti-PD1 and anti-CTLA-4 antibodies, how to translate this knowledge into more effective immune therapies in the future as well as how to augment effectiveness of current interventions (e.g., radiotherapy) is a challenge. Barriers to implementing this knowledge include cost of agents that release immune checkpoint blockade and coordination of cost-effective outpatient sarcoma treatment. Information on how to research clinical trial eligibility criteria and how to access current immune therapy trials against sarcoma are shared, too.
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PMID:Immune Therapy for Sarcomas. 2832 15

CASE DESCRIPTION A 12-year-old neutered male domestic shorthair cat had been treated for a mass arising from the lingual aspect of the caudal right mandibular body. Cytoreductive surgery of the mass had been performed twice over a 2-year period, but the mass recurred following both surgeries. The mass was diagnosed as an osteosarcoma, and the cat was referred for further evaluation and treatment. CLINICAL FINDINGS Clinical findings were unremarkable, except for a 2-cm-diameter mass arising from the lingual aspect of the right mandible and mild anemia and lymphopenia. Pre- and postcontrast CT scans of the head, neck, and thorax were performed, revealing that the osteosarcoma was confined to the caudal right mandibular body, with no evidence of lymph node or pulmonary metastasis. TREATMENT AND OUTCOME The stereolithographic files of the CT scan of the head were sent for computer-aided design and manufacture of a customized 3-D-printed titanium prosthesis. Segmental mandibulectomy was performed, and the mandibular defect was reconstructed in a single stage with the 3-D-printed titanium prosthesis. The cat had 1 minor postoperative complication but had no signs of eating difficulties at any point after surgery. The cat was alive and disease free 14 months postoperatively. CLINICAL RELEVANCE Reconstruction of the mandible of a cat following mandibulectomy was possible with computer-aided design and manufacture of a customized 3-D-printed titanium prosthesis. Cats have a high rate of complications following mandibulectomy, and these initial findings suggested that mandibular reconstruction may reduce the risk of these complications and result in a better functional outcome.
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PMID:Reconstruction of a mandibular segmental defect with a customized 3-dimensional-printed titanium prosthesis in a cat with a mandibular osteosarcoma. 2835 29