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

A link was proposed between human non-Hodgkin's lymphoma and exposure to 2,4,5-trichlorophenoxyacetic acid (245T) and pentachlorophenol (PCP). To test this view and the hypothesis that immune suppression or stimulation could affect B-cell lymphoma (BCL) induction, we administered chronically to MRC-Wistar (MRC-W) rats of both sexes 98% pure 245T (600 mg/kg diet), 86% pure PCP (500 mg/kg diet), methylprednisolone (20 mg/kg ip weekly), and Freund's adjuvant (0.5 ml im every 3-6 wk) for 40 wk, together with 75 mg 2-hydroxyethylnitrosourea (HENU)/l drinking water, a system known to induce B-cell lymphoma. The 245T was shown to contain only 1-4 micrograms/kg each of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), but the PCP contained 25 micrograms TCDD and 670 micrograms TCDF/kg. HENU given alone induced B-cell lymphoma and osteosarcoma as before, with higher incidences of both tumors in males than in females. The B-cell lymphoma diagnosis was confirmed by immunologic typing of cell-surface markers and by probes for gene rearrangements. Coadministration with HENU of three of the four test agents did not affect tumor incidence, but PCP acted synergistically with HENU to induce acute myelocytic leukemia. PCP given alone or with HENU induced a 40-67% incidence of liver cell adenomas in the female rats. These effects were probably not due to TCDD in the PCP. HENU induced acute myelocytic leukemia and lung tumors in Wistar rats and n-butylnitrosourea induced acute myelocytic leukemia in MRC-Wistar rats, indicating that B-cell lymphoma induction was specific to the HENU-MRC-Wistar rat model.
 ...
PMID:Effects of 2,4,5-trichlorophenoxyacetic acid, pentachlorophenol, methylprednisolone, and Freund's adjuvant on 2-hydroxyethylnitrosourea carcinogenesis in MRC-Wistar rats. 198 63

A previous report was made on the carcinogenicity of 1-(2-hydroxyethyl)-1-nitrosourea [(HENU) CAS: 13743-07-2] in rats. Because the cyclic nitrosocarbamate 3-nitroso-2-oxazolidinone (NOZ) is readily produced during the synthesis of HENU and can be confused with HENU, HENU was retested and NOZ was tested for carcinogenicity. Improved syntheses of both compounds are described. They were administered in drinking water to male MRC-Wistar rats for 1 year, starting at 3 or 9 weeks of age. The HENU-treated rats showed incidences of 48% for bone tumors, 32% for intestinal tumors (mostly duodenal adenocarcinomas), and 53% for lymphoma-leukemia. Of the bone tumors, which were evaluated microscopically and radiologically, 68% were osteosarcomas and 32% were osteoblastomas. The skeletal distribution of these tumors was similar to that of human osteosarcoma, with the tumors occurring most frequently in the lower limbs near the knees. Of the hematopoietic tumors, the majority were lymphoblastic lymphoma-leukemia, which showed a diffuse organ distribution resembling human B-cell (Burkitt's-like) lymphoblastic lymphoma-leukemia, and differed from the usual type of convoluted T-cell lymphoma-leukemia induced by other nitrosoureas in rats and mice. NOZ induced intestinal tumors (mostly duodenal adenocarcinomas) in 80% and liver tumors (mostly hepatocellular adenomas) in 53% of the rats.
 ...
PMID:Carcinogenicity of 1-(2-hydroxyethyl)-1-nitrosourea and 3-nitroso-2-oxazolidinone administered in drinking water to male MRC-Wistar rats: induction of bone, hematopoietic, intestinal, and liver tumors. 346

The overall incidence of osteosarcoma is low. However, the occurrence of osteosarcoma in a setting of multiple primary tumours is not infrequent, although population-based incidence numbers are unknown. The occurrence of osteosarcoma and other malignancies is frequently related to treatment, and can also be the result of genetic predisposition as in patients with retinoblastoma, Li-Fraumeni syndrome, Werner syndrome and Rothmund-Thomson syndrome. The aim of our study is to establish the incidence of osteosarcoma associated with other malignancies in a populationwide study and to find out if these osteosarcomas have a specific subtype, that could draw attention to a genetic predisposition to malignancy. A list of all patients registered in the Dutch National Pathology Register, named PALGA, with a diagnosis of osteosarcoma between 1975 and May 2000 was retrieved. All patients with another malignancy besides osteosarcoma were selected. All patients registered in the same period with a tonsillectomy served as a control for the occurrence of malignancy in a normal population. In a second step, only osteosarcoma patients with a history of retinoblastoma or a malignancy before the age of 46 years, since these are most probable to have a hereditary cancer syndrome, were retained for further analysis. The osteosarcomas were subtyped as common, chondroblastic, fibroblastic, teleangiectatic, anaplastic, osteoclast-rich or small cell. As a control for osteosarcoma subtypes the data of 570 patients entered in two studies from the European Osteosarcoma Intergroup (EORTC/MRC) were used. Of all 938 patients registered with the diagnosis of osteosarcoma, 66 had a history of multiple primary tumours. Four patients had a surface osteosarcoma, three an extraskeletal osteosarcoma and 59 had intramedullar high-grade osteosarcoma. Of this last group, one patient was known with Rothmund-Thomson syndrome, one had retinoblastoma and 30 had their malignancies before the age of 46. Of these 32 patients, 17 had osteosarcoma of the long bones. Especially women seem to be more susceptible for the development of multiple primaries. In nine patients, the histological subtype could be assessed by revision of available histological slides. All of these patients had an osteosarcoma subtype other than common as opposed to 29% in the control group of the European Osteosarcoma Intergroup. It is concluded that although the incidence of osteosarcoma is low, the occurrence of another malignancy in osteosarcoma patients is higher than in the normal population. Specifically, osteosarcoma patients have a relative risk of 2.4 (95% confidence interval 1.88-3.07) to develop another malignancy. A noncommon subtype of osteosarcoma should draw attention to a possible genetic predisposition of the patient involved.
 ...
PMID:Multiple primary malignancies in osteosarcoma patients. Incidence and predictive value of osteosarcoma subtype for cancer syndromes related with osteosarcoma. 1289 82

Purpose. To report the outcome of 37 patients with metastatic osteosarcoma entered into a large randomized trial (EOI 80831/MRC B002) comparing two different regimens of chemotherapy in patients with osteosarcoma.Methods. Patients with biopsy-proven osteosarcoma localized and metastatic, age 40 years or younger, were randomized to receive either two-drug treatment with doxorubicin/cisplatin (DOX 25 mg m(-2) day(-1) x 3 + DDP 100 mg m(-2) on day 1 q 3 weeks x 6 courses) or three-drug treatment comprising high-dose methotrexate (HDMTX 8 mg m(-2) administered every 4.5 weeks x 4 courses) given 10 days before DOX/DDP.Results. Twenty-four patients with metastatic disease received the two-drug arm treatment and 13 received three-drug treatment. Despite chance imbalance in numbers, there were no major differences in age, sex, primary site or performance status. Baseline alkaline phosphatase (AP) was elevated more frequently (96 vs 42%) in the two-drug arm. Twenty-one of 24 patients in the two-drug arm and 11/13 patients in the three-drug arm had evaluable primary tumors concurrent with metastases. Respective clinical response rates for the two- and three-drug arms were 48% and 40% for primary tumors, and 33% and 55% for metastases. Respective survivals at 2 and 4 years were 36% and 9% for the two-drug arm, and 69% and 52% for the three-drug arm, and survival was better for patients with normal AP at presentation. When adjusted for AP, survival was not significantly different between the two treatments (hazard ratio 0.52, 95% confidence interval 0.22-1.23, p = 0.14). There were three long-term survivors among the metastatic patients, all of whom received the three-drug therapy.Discussion. It is likely that random bias in the population (small numbers, imbalance in size of groups, uneven distribution of AP) accounts for the difference in outcome favoring the three-drug treatment in patients with metastatic disease. More reliance can be placed on the finding that disease-free and overall survival in the adjuvant component of this study (Bramwell et al., J Clin Oncol 1992; 10: 1579-91) were better after two-drug treatment.
 ...
PMID:A Randomized Comparison of two Short Intensive Chemotherapy Regimens in Children and Young Adults With Osteosarcoma: Results in Patients With Metastases: A Study of the European Osteosarcoma Intergroup. 1852 Dec 18