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)

Notch signaling plays crucial roles in many developmental pathways, with Notch mutations linked to several developmental disorders. Because many pediatric malignancies arise from dysregulated development, roles for Notch signaling in these cancers are to be expected. Evidence to support this is now emerging as the Notch pathway is being explored in more pediatric cancers. Not surprisingly, Notch appears to play diverse roles in different malignancies, effecting differentiation, metastasis, cancer "stem cells," and angiogenesis. As examples, although activating mutations of Notch1 are found in the majority of T-cell acute lymphoblastic leukemia (ALL) cases, Notch/HES1 signaling appears to play a tumor suppressor role in precursor B-cell ALL; although Notch/HES1 signaling appears to contribute to osteosarcoma metastasis, Notch signaling also promotes medulloblastoma "stem cell" survival and contributes to angiogenesis in neuroblastoma. Further understanding of the roles of Notch signaling in specific pediatric cancers will provide a rationale for Notch-based therapeutic strategies.
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PMID:Notch signaling in pediatric malignancies. 1892 60

Deletion or mutation of the SAP gene is associated with the X-linked lymphoproliferative disease (XLP) that is characterized by extreme sensitivity to Epstein-Barr virus (EBV). Primary infection of the affected individuals leads to serious, sometimes fatal infectious mononucleosis (IM) and proneness to lymphoma. Our present results revealed a proapoptotic function of SAP by which it contributes to the maintenance of T-cell homeostasis and to the elimination of potentially dangerous DNA-damaged cells. Therefore, the loss of this function could be responsible for the uncontrolled T-cell proliferation in fatal IM and for the generation of lymphomas. We show now the role of SAP in apoptosis in T and B lymphocyte-derived lines. Among the clones of T-ALL line, the ones with higher SAP levels succumbed more promptly to activation induced cell death (AICD). Importantly, introduction of SAP expression into lymphoblastoid cell lines (LCL) established from XLP patients led to elevated apoptotic response to DNA damage. Similar results were obtained in the osteosarcoma line, Saos-2. We have shown that the anti-apoptotic protein VCP (valosin-containing protein) binds to SAP, suggesting that it could be instrumental in the enhanced apoptotic response modulated by SAP.
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PMID:The proapoptotic function of SAP provides a clue to the clinical picture of X-linked lymphoproliferative disease. 1957 Sep 96

A 48-year-old man was referred for left pulmonary metastasis and a left pulmonary artery embolus. The patient had T-cell acute lymphoblastic leukemia and fibroblastic osteosarcoma. A left pneumonectomy was performed successfully and the histologic report concluded that an embolic deposit of osteosarcoma was present. Pulmonary artery tumor embolism is a rare presentation in patients with previous fibroblastic osteosarcoma. It is important to suspect this diagnosis in a patient with cancer who presents with a pulmonary artery embolus.
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PMID:Pulmonary artery tumor embolism in a patient with previous fibroblastic osteosarcoma. 2370 36

(-)-Agelastatin A (AglA, 1), a member of the pyrrole-aminoimidazole marine alkaloid (PAI) family, possesses a unique tetracyclic structure and is one of the most potent anticancer PAIs isolated to date. In efforts to expand the SAR of these agents and delineate sites that tolerate modification while retaining activity, we synthesized several derivatives and tested their anticancer activity. The cytotoxic effects of these derivatives were measured against several cancer cell lines including cervical cancer (HeLa), epidermoid carcinoma (A431), ovarian (Igrov and Ovcar3), osteosarcoma (SJSA1), acute T cell leukemia (A3), epidermoid carcinoma (A431) in addition to primary human chronic lymphocytic leukemia (CLL) cells. New positions for modification of AglA and new substitutions were explored leading to novel derivatives, 14-chloro AglA (3) and 14-methyl AglA (12), that retained activity toward various cancer cell lines with decreased toxicity toward B- and T-cells. The SAR data informed the synthesis of a trifunctional probe bearing an alkyne and a diazirine potentially useful for cellular target identification.
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PMID:Derivatization of agelastatin A leading to bioactive analogs and a trifunctional probe. 2695 51