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)

81 candidate families with a rare genetic susceptibility to cancer called Li-Fraumeni syndrome were enrolled in an International Working Group. Review of 2,261 blood relatives revealed a total of 515 family members (23%) who had at least one confirmed cancer diagnosis. The major features of the syndrome, breast cancer, sarcomas of soft tissue and bone, brain tumour, leukemia and adrenal cortical carcinoma accounted for 74% of all the cancers recorded. 64% of all malignant tumours occurred before the age of 45 years. Among females, breast cancer accounted for 43 percent of all cases. There were 22 cases of bilateral metachronous breast cancer. Excluding individuals with bilateral breast cancer, 76 patients developed a second neoplasm, the most common being osteogenic sarcoma. The present study agrees with previous reports on the epidemiological aspects of Li-Fraumeni syndrome, the genetic defect of which has recently been found to involve the tumour-suppressor gene p53.
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PMID:[Li-Fraumeni syndrome and the p53 gene]. 155 56

The antitumor effects of 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine (CN-DAC), a synthetic 1-beta-D-arabinofuranosyl-cytosine (ara-C) derivative, were examined and compared with that of ara-C in murine tumors and in various human tumors using three different chemosensitivity tests. CNDAC extended the life span of mice bearing P388 leukemia. CNDAC had a unique in vitro antitumor spectrum for human cancers different from that of ara-C. Compared with ara-C, CNDAC was more effective in 10 human tumors (2 lung, 4 stomach and 4 osteosarcoma), equal in 2 tumors (lung and fibrosarcoma) and less potent in 11 tumors (4 lung, 4 osteosarcoma, bladder, renal and epidermoid). Characteristically CNDAC showed excellent activities against tumors, refractory to ara-C, such as HT-1080 human fibrosarcoma implanted in chick embryos or athymic mice, although its cytotoxicity against HT-1080 was almost equal to that of ara-C. Thus, CNDAC is an interesting and promising agent that should be considered for further detailed preclinical evaluation.
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PMID:Antitumor activity of a novel nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D-arabinofuranosylcytosine (CNDAC) against murine and human tumors. 159 80

2,3-Dihydrophthalazine-1,4-dione derivatives demonstrated potent cytotoxicity against the growth of murine leukemia cells and human single cell suspension, i.e. Tmolt3 leukemia and HeLa-S3, as well as colon adenocarcinoma and KB nasopharynx. However, only select compounds demonstrated activity against bronchogenic lung, osteosarcoma and glioma growth. 2,3-Dihydrophthalazine-1,4-dione was active in vivo against L1210 leukemia, Lewis lung and Ehrlich ascites carcinoma growth. In L1210 cells the agents inhibited both DNA and RNA synthesis, and a few of the compounds were capable of inhibiting protein synthesis at 3 times their ED50 values. When 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione were examined for their mode of action in the L1210 lymphoid leukemia cells, the sites of inhibition by the agents appear to be the de novo purine pathway at the enzymes IMP dehydrogenase and PRPP amido transferase. IMP dehydrogenase activity was inhibited at least 45% by 45 min at 100 microM concentration of drugs whereas the remaining enzymes that were affected by the drugs were not inhibited as early. Secondary sites were dihydrofolate reductase and thymidylate synthetase. The d(NTP) levels were also reduced specifically dATP and dCTP levels.
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PMID:The anti-neoplastic activity of 2,3-dihydrophthalazine-1,4-dione and N-butyl-2,3-dihydrophthalazine-1,4-dione in human and murine tumor cells. 162 17

Efforts to diminish the overall morbidity and mortality of malignancy have required a variety of strategies and a balanced national research agenda. The design of curative regimens against leukemia, lymphomas, testis cancer, and childhood malignancies is a tribute to the interactions between laboratory and clinical scientists. Laboratory models illustrated the importance of dose and the need for combinations to avoid the emergence of drug resistance in heterogeneous tumors. In addressing the incurability of common epithelial cancers in adults once disseminated, again laboratory models suggested that regimens which produced responses in advanced disease might be curative in patients with micro-metastases. Such proved to be the case in adjuvant therapy for breast cancer involving lymph nodes and for osteogenic sarcoma. Recent studies have extended this strategy to less advanced breast cancer and to locally advanced colon cancer. Lung cancer has required a different strategy. A coalition has developed to support the strongest possible public position against smoking. For the first time lung cancer incidence has leveled off in white males. Women and minorities continue to be a major target for smoking cessation programs. While large randomized trials are expensive (and to some scientists, unexciting), they are our most reliable means of detecting treatment differences of 10 to 15%. Because lung, breast, and colon cancer kill almost 250,000 Americans each year, such "small" differences represent thousands of Americans. There are also a number of interesting current studies that may impact in the longer term on the care of patients with cancer. Research of three different groups of investigators has recently converged. Over the past 3 decades several groups of basic laboratory investigators had been studying and cloning hematopoietic growth factors. Large randomized trials now confirm that myelosuppression after intensive chemotherapy can be substantially ameliorated, reducing infections and decreasing hospital days, risks, and costs. Another cohort of clinical pharmacologists and clinicians were studying bone marrow transplantation, developing combinations of agents that can be given at high dose to overcome resistance, albeit with considerable toxicity. Other groups in blood banks and those interested in the regulation of hematopoiesis recognized that early hematopoietic progenitor cells circulate in the peripheral blood. Their number were increased after certain chemotherapy regimens, by growth factors and most remarkably, with growth factors given after chemotherapy. Patients supported with peripheral blood progenitor cells reengraft both platelets and granulocytes more rapidly than those given marrow, in the time frame of recovery after standard doses of chemotherapy (i.e., 21 days).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:New developments in clinical oncology: the interdependence of bench and bedside. 167 75

Acute nonlymphocytic leukemia (ANLL) developed in 2 of 142 pediatric patients with osteosarcoma treated with a cis-diamminedichloroplatinum-II (CDP)-based regimen: acute monomyelogenous leukemia (M4) with a normal female karyotype in one and acute myelogenous leukemia (M2) with t (8,21) in the other. The ANLLs occurred, respectively, in each patient 3 and 4 years after the initial diagnosis of osteosarcoma. In contrast to most of the adult experience and consistent with the majority of reported ANLL in children, the disease was characterized by an absence of the smoldering phase and cytogenetic findings similar to those seen in de novo ANLL.
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PMID:Secondary acute non-lymphoblastic leukemia in two children following treatment with a cis-diamminedichloroplatinum-II-based regimen for osteosarcoma. 172 15

We isolated four monoclonal antibodies (MAbs), M38, M101, M104, and C33, which were capable of inhibiting syncytium formation induced in a human T-cell line, MOLT-4-#8, by coculture with human T-cell leukemia virus type 1 (HTLV-1)-positive human T-cell lines. The MAbs had, however, no inhibitory activity on syncytium formation induced in a human osteosarcoma line, HOS, by HTLV-1-positive T-cell lines. They also did not inhibit syncytium formation induced in MOLT-4-#8 by human immunodeficiency virus type 1-positive MOLT-4. All MAbs reacted with various human cell lines of lymphoid and nonlymphoid origins, including HTLV-1-positive T-cell lines. Furthermore, they all reacted with a murine A9 clone containing human chromosome 11 fragment q23-pter. Two MAbs, M104 and C33, immunoprecipitated a membrane antigen with the same molecular size. The antigen (henceforth called C33 antigen) was about 40 to 55 kDa in HTLV-1-negative Jurkat, CEM, MOLT-4, and normal peripheral blood CD4-positive human T cells and about 40 to 75 kDa in HTLV-1-positive C91/PL, TCL-Kan, MT-2, and in fresh HTLV-1-transformed CD4-positive human T-cell lines. Pulse-chase experiments revealed that C33 antigen was synthesized as a 35-kDa precursor that was then processed to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL. In the presence of tunicamycin, a 28-kDa protein was synthesized. The conversion from 35 kDa to 41 to 50 kDa in MOLT-4 and to 44 to 70 kDa in C91/PL was inhibited by monensin. Treatment with N-glycanase alone, but not with sialidase and O-glycanase in combination, completely removed the sugar moiety of C33 antigen from both HTLV-1-negative Jurkat and HTLV-1-positive C91/PL. Therefore, C33 antigen has only N-linked carbohydrates, the modification of which appears to be substantially altered in the presence of the HTLV-1 genome.
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PMID:Identification of membrane antigen C33 recognized by monoclonal antibodies inhibitory to human T-cell leukemia virus type 1 (HTLV-1)-induced syncytium formation: altered glycosylation of C33 antigen in HTLV-1-positive T cells. 173 99

Flavonolignans isolated from Hydnocarpus wightiana seeds, namely hydnowightin, hydnocarpin, and neohydnocarpin, demonstrated potent hypolipidemic activity in mice, lowering both serum cholesterol and triglyceride levels at 8 mg/kg/day ip. Hydnowightin demonstrated the best lipid-lowering effect of the three compounds. Good anti-inflammatory and antineoplastic activity was demonstrated by hydnocarpin in mice in vivo. The other two derivatives were not as active in these screens. Cytotoxicity against the growth of murine and human tissue cultured cells was shown. All three compounds were moderately active against murine L-1210 leukemia growth. All three compounds demonstrated good activity against the growth of human KB nasopharynx, colon adenocarcinoma, osteosarcoma, and HeLa-S3 uterine growth. Hydnocarpin was the only compound of the three which was active against glioma growth. Hydnocarpin and neohydnocarpin demonstrated significant activity against Tmolt3 leukemia cell growth.
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PMID:Hypolipidemic, anti-inflammatory, and antineoplastic activity and cytotoxicity of flavonolignans isolated from Hydnocarpus wightiana seeds. 180 Jun 32

Boron analogues of piperidine, piperazine, morpholine, and imidazole proved to be cytotoxic against the growth of murine and human tissue culture cells. Significant activity was demonstrated for single-cell suspensions of L1210 lymphoid leukemia, Tmolt3 lymphoblastic leukemia, and HeLa-S3 cervical carcinoma. Trimethylamine-imidazole carbonyldihydroborane 17 demonstrated activity against solid tumor growth of human colorectal adenocarcinoma, KB nasopharynx, and osteosarcoma. In addition, 4-methylpiperidine-carbomethoxyborane 12, 2-methylimidazole-3-cyanoborane 16, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were active against the KB nasopharynx growth. Piperidine-cyanoborane 2, piperidine-carboxyborane 4, and 1-methylimidazole-3-(N-ethylcarbamoyl)borane 19 were effective in reducing the growth of osteosarcoma cells. The imidazole derivatives 13-19, as well as 4-methylpiperidine-carboxyborane 11 and carbomethoxyborane 12, demonstrated good activity against lung bronchogenic and glioma growth. In the in vivo studies, N-methylmorpholine-carboxyborane 7,4-phenylpiperidine-carboxyborane 9, 4-phenylpiperidine-carbomethoxyborane 10, 4-methylpiperidine-carboxyborane 11, imidazole cyanoborane 14, and 1-methylimidazole-3-carbomethoxyborane 18 demonstrated the best activity against Lewis Lung growth and P388 lymphocytic leukemia growth in mice. Mode of action studies in L1210 leukemia cells demonstrated that piperidine-carboxyborane 4 and N-methylmorpholine-carboxyborane 7 inhibited DNA synthesis, purine synthesis at PRPP amido transferase and IMP dehydrogenase sites, and thymidine kinase and thymidine diphosphate kinase activities, while lowering d(NTP) pool levels. Also, DNA strand scission was evident after incubation with these drugs.
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PMID:Synthesis and antineoplastic activity of some cyano-, carboxy-, carbomethoxy-, and carbamoylborane adducts of heterocyclic amines. 181 71

This study explores the relationship between histologic variants of bone sarcomas and previous therapy in patients in whom an unrelated malignant neoplasm had been diagnosed during childhood. Sarcomas of bone were the most common second malignant neoplasm (SMN) reported to the Late Effects Study Group, a 13-institution consortium consisting of pediatric oncology centers from western Europe, Canada, and the United States. The authors attempted to relate the histologic subtypes of the 91 bone tumors to clinical factors such as previous therapy and genetic predisposition because morphologic variants have been shown to have biologic significance in other tumors and may have etiologic import. The literature concerning the subtypes of bone tumors, clinical and experimental, is also reviewed. The authors also investigated the effect of several factors on the time interval from the first diagnosis to the SMN (i.e., the bone sarcoma). Anthracyclines significantly shortened the interval by about 3 years. The primary diagnosis also significantly affected the interval, with leukemia/lymphomas having the shortest interval and retinoblastoma the longest. The authors could not demonstrate any significant relationship between morphologic characteristics of the osteosarcoma and predisposing conditions. However, lesions diagnosed as chondrosarcoma and malignant fibrous histiocytoma occurred almost exclusively in patients who had received radiation therapy to the site in which the SMN developed.
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PMID:Bone sarcomas as second malignant neoplasms following childhood cancer. 198 16

Magnetic resonance imaging (MRI) is a sensitive method for the diagnosis of bone marrow abnormalities, but its usefulness in detecting active disseminated cancer in this tissue in treated patients has not been determined. We therefore examined 14 children who had been treated for disseminated bone marrow involvement by neuroblastoma (n = 6), lymphoma (n = 3), Ewing's sarcoma (n = 3), osteosarcoma (n = 1), and leukemia (n = 1). MRI studies were performed at 21 marrow sites to evaluate residual or recurrent tumor and were correlated with histologic material from the same site. T1- and T2-weighted sequences were employed in 21 and 14 studies, respectively; short tau inversion recovery (STIR) in 18; and static gadolinium diethylene triamine pentaacetic acid (Gd-DPTA)-enhanced. T1-weighted sequences in 13. All MRI studies showed an altered bone marrow signal. Technetium 99m methylene diphosphonate (99mTc-MDP) bone scintigraphy was also performed (19 studies). On histologic examination, 7 marrow specimens contained tumor, and 14 did not. Of the 7 tumor-positive lesions, all T1-weighted, 4 of 6 T2-weighted, and all 6 STIR sequences showed abnormal signal; all 5 Gd-DTPA-enhanced. T1-weighted sequences showed enhancement of the lesion. However, abnormal signals were also observed on all T1-weighted, 6 of 8 T2-weighted, 11 of 12 STIR, and 5 of 8 Gd-DTPA-enhanced, T1-weighted images of the tumor-negative sites. In this clinical setting, MRI did not consistently differentiate changes associated with treatment from malignant disease.
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PMID:Magnetic resonance imaging of disseminated bone marrow disease in patients treated for malignancy. 202 Aug 67


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