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)

A search of the records of 10 pediatric oncology centers revealed 102 children with more than one malignant neoplasm. In this group of 102 patients, all pediatric cancers were seen as initial lesions, but Wilms' tumor and retinoblastoma were over-represented and leukemia and brain tumors underrepresented. Survival variation as well as tumor susceptibility may be responsible for this disproportion. Osteosarcomas and chondrosarcomas were the most frequent second malignant neoplasms (SMN). Embryonal tumors were rare as SMN and adult-type tumors (carcinomas) appeared at earlier than expected ages, whether arising after irradiation or not related to that form of therapy. Radiation was associated with 69 SMN, genetic disease accounted for 27 SMN and both conditions were noted in 15 SMN. In the group of 21 patients for whom neither radiation nor a known genetic disorder could be implicated, there were three with colon carcinoma and glioma and five with leukemia or lymphoma and glioma. These combinations may reflect new tissue-specific hereditary cancer syndromes.
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PMID:Patterns of second malignant neoplasms in children. 19 10

In the 1970s chemotherapy has been successfully incorporated into curative primary treatment programs for various adult malignancies so that it is no longer solely palliative treatment for advanced disease. For at least three malignancies and tentatively a fourth (breast and colon carcinoma, osteosarcoma, and melanoma), certain groups of patients have had longer disease-free survival produced by the use of chemotherapy after surgical removal of the primary lesion. The potential impact on cancer mortality from these treatment results is obvious. We review here the fundamental laboratory concepts that have led to human trial of multimodal primary therapy regimens. Data from numerous clinical trials are analyzed, with delineation of the problems encountered in the interpretation of their results.
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PMID:Multimodal primary cancer treatment (adjuvant chemotherapy): current results and future prospects. 38 Apr 37

Endothelial leukocyte adhesion molecule-1 (ELAM-1) has been determined to be the mediator of adhesion of colon carcinoma cells to interleukin-1 (IL-1)-activated endothelial cells. To identify ELAM-1 ligand in colon carcinoma cells, we have screened a series of 11 monoclonal antibodies directed to these cells and found that only one MBr8 was able to inhibit the IL-1-induced increment in adhesion of HT29 and of SW948 colon carcinoma lines to endothelial cells. In contrast, MBr8 did not bind to polymorphonuclear cells, monocytes, and lymphocytes and did not inhibit polymorphonuclear adhesion to IL-1-activated endothelial cells. As expected, an ELAM-1 monoclonal antibody strongly inhibited IL-1 induced increment of adhesion of HT29, SW948, and polymorphonuclear cells. As negative control, MG63 osteosarcoma cells were used. These cells adhere more efficiently to IL-1 activated endothelial cells but MBr8 and ELAM-1 monoclonal antibodies did not affect their adhesion. The effect of MBr8 was also tested in an experimental system in vivo. As described previously, radiolabeled HT29 cell retention in the lung of nude mice was increased in animals given IL-1. MBr8 administration to nude mice or pretreatment of tumor cells with it inhibited this effect. These data suggest that cell adhesion to ELAM-1 might be mediated by different, cell type specific, sugar ligands.
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PMID:Endothelial leukocyte adhesion molecule-1-dependent adhesion of colon carcinoma cells to vascular endothelium is inhibited by an antibody to Lewis fucosylated type I carbohydrate chain. 137 72

Reviewing the treatment perspectives with chemo- and immunotherapy in carcinomas and sarcomas to be treated by general or orthopedic surgeons, the following indications are regarded as recommendable: Adjuvant chemotherapy in breast cancer, neoadjuvant chemotherapy with radiation in anal carcinoma and neoadjuvant/adjuvant chemotherapy of high-grade malignant osteosarcoma. Isolation perfusion currently is the treatment of choice in melanoma metastasis limited to an extremity. With several indications, recent developments have produced promising results that should be urgently confirmed in appropriate studies. Therefore the following studies have a high priority: Neoadjuvant chemotherapy in esophageal carcinoma and in locally advanced breast and stomach cancer, adjuvant chemoimmunotherapy in colon carcinoma UICC III and chemoradiation in rectal carcinoma UICC II and III, systemic chemotherapy of metastasized stomach-, colorectal-, breast cancer and sarcomas. Isolated non-resectable liver metastases of colorectal origin and hepatocellular carcinoma should be included in studies evaluating the treatment advantage of regional chemotherapy. Those malignant "surgical" tumors not listed above should receive chemotherapy within experimental studies, after consideration of individual risk factors, or no chemotherapy. Immunotherapy with its various modalities is still in the experimental stage.
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PMID:[What is confirmed in chemo- and immunotherapy of solid tumors. Standard protocols, studies and new developments]. 160 55

Activation of endothelial cells by the two inflammatory mediators interleukin-1 (IL-1) and tumor necrosis factor strongly increases tumor cell adhesion. We describe antibody inhibition studies showing that the endothelial leukocyte adhesion molecule-1 (ELAM-1), a cell-surface glycoprotein selectively expressed by cytokine-activated endothelial cells and responsible for neutrophil adhesion, is the major, if not the only, mediator of colon carcinoma cell adhesion to activated endothelial cells. Among the different tumor cell lines tested, seven colon carcinoma cell lines were sensitive to ELAM-1 antibodies. Adhesion of melanoma, osteosarcoma, and lung, cervix, or kidney carcinoma cell lines to IL-1-treated endothelial cells was not affected by the ELAM-1 antibody. This result suggests that ELAM-1 is selectively recognized by colon carcinoma cells and that adhesion of tumor cells to activated endothelial cells could be mediated by different and specific mechanisms.
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PMID:Tumor cell adhesion to endothelial cells: endothelial leukocyte adhesion molecule-1 as an inducible adhesive receptor specific for colon carcinoma cells. 171 24

Hematogenous metastasis involves adhesive interactions between blood-borne tumor cells and the vessel wall. By the use of in vitro assays, the adhesion of human melanoma, osteosarcoma, and kidney carcinoma (but not colon carcinoma) cell lines was shown to involve the cytokine-inducible endothelial cell surface protein inducible cell adhesion molecule 110 (INCAM-110) and the alpha 4 beta 1 integrin, molecules normally involved in endothelial-leukocyte interactions. Tumor adhesion to human endothelial cell monolayers was increased 1.9- to 8.2-fold by endothelial activation with the cytokine tumor necrosis factor (TNF) and inhibited by the anti-INCAM-110 monoclonal antibody (mAb) E1/6. Each of these tumor cells expressed members of the beta 1 integrin family of adhesion molecules, and antibodies to the alpha 4 and beta 1 integrin subunits inhibited tumor-endothelial adhesion (48-87% inhibition). A cDNA encompassing the three N-terminal Ig-like domains of vascular cell adhesion molecule 1 (VCAM-1) encoded a protein recognized by the anti-INCAM-110 mAb E1/6 and, when captured onto plastic, supported melanoma cell adhesion by an alpha 4 integrin-dependent mechanism. In contrast to mAb E1/6, a second anti-INCAM-110 mAb Hu8/4 neither inhibited adhesion to activated endothelium nor bound the first three Ig-like domains of INCAM-110/VCAM-1. These data indicate that the adherence of several human tumors to activated endothelium is mediated by an interaction of alpha 4 beta 1 integrin and the N-terminal Ig-like domains of endothelial INCAM-110/VCAM-1. Tumor acquisition of the alpha 4 integrin subunit and endothelial expression of INCAM-110 may affect the frequency and distribution of metastasis.
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PMID:Tumor cell surface alpha 4 beta 1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1. 171 64

We investigated the effects of beta 1 integrins on tumor cell (TC) adhesion to unstimulated and interleukin-1 (IL-1) activated endothelial cells (EC). IL-1 treatment (20 units/ml for 6 hours) of cultured human umbilical vein EC significantly increased adhesion of seven human TC lines of different origin. A goat antiserum raised to purified alpha 5 beta 1 integrin abolished the IL-1 induced increment in adhesion of two osteosarcomas, one melanoma, one lung, and one kidney carcinoma, whereas it did not affect adhesion of two colon carcinoma cell lines. Further studies were performed on MG63 osteosarcoma cells. Adhesion of MG63 osteosarcoma cells to EC was dependent on time of EC treatment with IL-1: it was maximal at 12 hours and declined at 24 hours. alpha 5 beta 1 antiserum blocked IL-1 induced increase in MG63 adhesion at any time of EC treatment. This effect appears to be mainly directed to MG63 integrins since selective incubation of the antiserum with EC, but not with MG63, did not modify TC adhesion. Using a series of antibodies to different alpha and beta chains, we found that only monoclonal antibodies (mAb) to alpha 4, alpha 5, and beta 1 could inhibit MG63 adhesion to IL-1 activated EC, whereas alpha 2, alpha 6, and beta 3 antibodies were ineffective. Antibodies to fibronectin had very little activity on MG63 adhesion to EC matrix and did not significantly affect MG63 adhesion to control or IL-1 treated EC. Antibodies to alpha 4, alpha 5, and beta 1 were only partially effective in inhibiting MG63 adhesion to EC matrix. These data indicate that the capacity of alpha 4 beta 1 and alpha 5 beta 1 integrins to bind fibronectin contributed very little to MG63 adhesion to EC. The importance of beta 1 integrins in promoting a direct interaction between EC and MG63 was further shown by inhibition of rosette formation among these cells in suspension by the alpha 5 beta 1 antiserum. Only a VCAM-1/INCAM110 mAb, but not ELAM-1 or ICAM-1 mAbs, could inhibit MG63 adhesion to IL-1 activated EC. Overall these data indicate that at least two members of the beta 1 integrin subfamily (alpha 4 beta 1 and alpha 5 beta 1) are involved in MG63 adhesion to cytokine treated EC. This integrin function might be important at early stages of TC interaction with the vessel wall.
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PMID:Role of beta 1 integrins in tumor cell adhesion to cultured human endothelial cells. 175 2

Partially thiolated polycytidylic acid (5-mercaptopolycytidylic, MPC) and its double-stranded complex with polyinosinic acid [poly (I)].poly(I).MPC, were assayed in both antiproliferative and cytotoxicity tests against human cell lines: lung carcinoma A549, colon carcinoma HT-29, osteosarcoma HOS, and amnion cells (WISH). Inhibitory effects of MPC were noted in the antiproliferative assay with ID50 of 7, 24, 33, and 35 micrograms.ml-1, and in the cytotoxicity test with ID50 of 164, 174, 210, and 290 micrograms.ml-1 against the HOS, A549, HT-29, and WISH cells respectively. Comparison with the corresponding partially thiolated mononucleotide (5-mercapto-CMP + CMP) and the nucleoside (5-mercapto-cytidine) demonstrated that MPC was a more potent antiproliferative agent than either of its monomeric constituents. The inhibitory effect of MPC upon the incorporation of [3H]thymidine into the DNA of growing A549 cells paralleled its antiproliferative activity.
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PMID:Inhibition of human cancer cell lines in vitro with mono- and polynucleotides containing 5-mercaptocytosine bases. 177 73

Twelve women and 7 men, median age 58 (range 17-74), with a diagnosis of non-small-cell lung cancer (11 patients), inflammatory breast cancer (5 patients), osteosarcoma (2 patients), and colon carcinoma (1 patient) were studied. Treatment consisted of four consecutive 6-day courses of infusional interleukin-2 (IL2); 9 patients were treated with 20 X 10(6) IU/m2/day and 10 patients received weekly dose increments of 50% until the maximally tolerated dose was reached. One day after each course was completed patients received doxorubicin, 30 mg/m2; infusional IL2 was resumed 24 h after receiving doxorubicin. Rebounds of lymphocytes with high spontaneous synthetic rates of DNA occurred one day after stopping the infusion, despite doxorubicin administration. The kinetics were not different from earlier trials using IL2 alone. Sequential lymphocyte analysis showed that helper (CD4) and suppressor (CD8) T-cell subsets increased after the first week of treatment and declined thereafter, whereas the proliferation of natural killer (NK) cells (CD16) progressed through the 4-week treatment unaffected by doxorubicin. Mean cytolytic ability induced by IL2 against NK-resistant tumors in vitro was higher in patients who had evidence of clinical tumor regression and therefore is prognostically valuable (p = .02). Three patients left the study prematurely. Five partial remissions and 2 minimal responses were seen in the remaining 16 patients, but they were short-lived. Of the responding patients, only one had failed prior doxorubicin-containing chemotherapy. Toxicities attributable to IL2 and doxorubicin were encountered, and were manageable at these doses. Our data suggest that doxorubicin did not have cytotoxic or suppressive effects on lymphokine-induced lymphocyte functions and that both treatment modalities in combination are worthy of further investigation since they exert distinct and compatible cytotoxic mechanisms and induced tumor regressions with acceptable toxicity in a group of patients with poorly responsive cancers.
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PMID:Immunotherapy with IL2 by constant infusion and weekly doxorubicin. 183 Jul 17

The two naturally occurring forms of ricin A chain, Mr 33,000 and Mr 30,000 (RTA33 and RTA30) have been purified, and their chemical compositions, toxicities, and tissue distributions have been determined. As reported previously, the in vitro and in vivo toxicities of RTA30 and RTA33 are similar. However, RTA30, which contains less carbohydrate with a lower mannose content than RTA33, accumulated less in the liver than did RTA33. Monoconjugate immunotoxins (i.e., containing one RTA per monoclonal antibody molecule) were constructed between RTA30 or RTA33 and the antitumor monoclonal antibody 791T/36, which recognizes a Mr 72,000 antigen on osteosarcoma and colon carcinoma cells. The two immunotoxins had similar cytoxicities in vitro but differed substantially in their pharmacokinetics and tissue distributions in vivo in nude mice bearing C170 human colorectal carcinoma xenografts. The immunotoxin derived from RTA30 (IT30) accumulated less in the liver than the immunotoxin derived from RTA33 (IT33) and cleared more slowly from the blood; the alpha and beta half-lives for IT30 and IT33 were 0.50 and 20.5 versus 0.17 and 14.6 h, respectively. As a probable consequence, IT30 accumulated to approximately 3-fold higher levels in the C170 xenografts than IT33. The reduced clearance of IT30 by the reticuloendothelial system thus resulted in prolonged survival in the blood and enhanced tumor localization relative to IT33.
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PMID:Improved pharmacokinetics and tumor localization of immunotoxins constructed with the Mr 30,000 form of ricin A chain. 186 42


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