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 32-year-old black man was observed with osteosarcoma and multiple anomalies including deafness, hypopigmentation, cataracts, small head size, hypogonadism, and restricted joint mobility. The birth defects may comprise a new syndrome or combination of syndromes, of which the malignancy may be a part.
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PMID:Waardenburg-like features with cataracts, small head size, joint abnormalities, hypogonadism, and osteosarcoma. 27 99

Dose-dependent reduction of auditory function mainly in the high frequency range has been described as a common adverse side effect of cis-platinum. Here we report on a 4-year-old girl with osteosarcoma of the right distal femur who developed acute bilateral deafness 3 days after a single infusion of high-dose cis-platinum (150 mg/m2) during preoperative chemotherapy. Sudden disabling ototoxicity should be considered when administering high-dose cis-platinum to young children.
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PMID:Acute onset deafness in a 4-year-old girl after a single infusion of cis-platinum. 220 55

Cisplatin was used in 14 bone and soft tissue sarcomas. Severe vomiting developed in all cases, but the duration was relatively short. Renal function was disturbed in cases with a higher total dose. This side effect was considered to be the dose-limiting factor of cisplatin. Seven cases showed high-frequency deafness but they did not complain of disturbance during conversation. In seven metastatic osteosarcomas, one was evaluated as a partial response and one as a minor response. No response was observed among three soft tissue sarcomas. Three cases of osteosarcoma receiving cisplatin in adjuvant chemotherapy have been disease-free for 4 and 46 months after resection of pulmonary metastases and for 50 months after resection of the primary tumor. We consider cisplatin to be the first-choice drug in cases resistant to adriamycin or methotrexate, but there are some problems when cisplatin is used in adjuvant chemotherapy, because of its side effects.
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PMID:[Chemotherapy using cisplatin in bone and soft tissue sarcoma]. 346 52

The nucleotide pair (np) 7472 insC mitochondrial DNA mutation in the tRNA(Ser)(UCN) gene is associated with sensorineural deafness, combined in some individuals with a wider syndrome including ataxia and myo-clonus. Previous studies in osteosarcoma cell cybrids revealed only a mild respiratory defect linked to the mutation. We have investigated the biochemical and molecular consequences of the mutation, using a panel of seven osteosarcoma cell cybrids containing 100% mutant mtDNA, plus two cybrids carrying 100% wild-type mtDNA from the same patient. The mutation is associated with a mild growth deficit in selective (galactose) medium that is only significant in combination with a reduced mtDNA copy number, suggesting a mechanism that might modulate clinical phenotype. The mutation results in a 65% drop in the steady-state level of tRNA(Ser)(UCN), but causes at most only a very mild and quantitative abnormality of mitochondrial protein synthesis, associated with modest hypersensitivity to doxycyclin. No evidence for a specific defect in aminoacylation was obtained, and unlike the case with the np 7445 mutation, the pattern of RNA processing of light strand transcripts of the ND6 region was not systematically altered. Comparing the np 7472 and np 7445 mutant phenotypes in cultured cells suggests that sensorineural deafness can result from a functional insufficiency of mitochondrial tRNA(Ser)(UCN), to which some cells of the auditory system are especially vulnerable.
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PMID:Molecular phenotype of the np 7472 deafness-associated mitochondrial mutation in osteosarcoma cell cybrids. 1054 8

The pathogenic mechanisms of the A1555G mitochondrial DNA mutation in the 12S rRNA gene, associated with maternally inherited sensorineural deafness, are largely unknown. Previous studies have suggested an involvement of nuclear factor(s). To address this issue cybrids were generated by fusing osteosarcoma cells devoid of mtDNA with enucleated fibroblasts from two genetically unrelated patients. Furthermore, to determine the contribution, if any, of the mitochondrial and nuclear genomes, separately or in combination, in the expression of the disease phenotype, transmitochondrial fibroblasts were constructed using control and patient's fibroblasts as nuclear donors and homoplasmic mutant or wild-type cybrids as mitochondrial donors. Detailed analysis of mutant and wild-type cybrids from both patients and transmitochondrial fibroblast clones did not reveal any respiratory chain dysfunction suggesting that, if nuclear factors do indeed act as modifier agents, they may be tissue-specific. However, in the presence of high concentrations of neomycin or paromomycin, but not of streptomycin, mutant cells exhibit a decrease in the growth rate, when compared to wild-type cells. The decrease did not correlate with the rate of synthesis or stability of mitochondrial DNA-encoded subunits or respiratory chain activity. Further studies are required to determine the underlying biochemical defect.
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PMID:Pathogenesis of the deafness-associated A1555G mitochondrial DNA mutation. 1205 32

A heteroplasmic T to C transition at nucleotide position 14709 in the mitochondrial tRNA glutamic acid (tRNA(Glu)) gene has previously been associated with maternally inherited diabetes and deafness (MIDD). To investigate the pathogenic mechanism of the T14709C mutation, we have constructed transmitochondrial cell lines by transferring fibroblasts mitochondria from a patient with the mutation into human cells lacking mitochondrial DNA (mtDNA) (rho degrees cells). Clonal cybrid cell lines were obtained containing various levels of the heteroplasmic mutation, or exclusively mutated or wild-type mtDNA. Measurement of respiratory chain enzymatic activities failed to detect a difference between the homoplasmic mutant and homoplasmic wild-type cybrid cell lines. However, a subtle decrease in the steady-state levels of tRNA(Glu) transcripts in some mutant clones. Our studies suggest that the T14709C mutation is insufficient to lead impairment of mitochondrial function in homoplasmic osteosarcoma cybrid clones, and that we cannot exclude that the T14709C mutation affects mitochondrial function by a yet unidentified mechanism.
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PMID:Molecular and functional effects of the T14709C point mutation in the mitochondrial DNA of a patient with maternally inherited diabetes and deafness. 1239 75

The deafness-associated A7445G mutation in the precursor of mitochondrial tRNA(Ser(UCN)) has been identified in several pedigrees from different ethnic backgrounds. To determine the role of nuclear background in the biochemical manifestation associated with the A7445G mutation, we performed a biochemical characterization of this mutation using cybrids constructed by transferring mitochondria from lymphoblastoid cell lines derived from a New Zealand family into human osteosarcoma mtDNA-less (rho(0)) cells. Compared with three control cybrids, three cybrids derived from an affected matrilineal relative carrying the homoplasmic A7445G mutation exhibited approximately 38-57% decrease in the steady-state level of tRNA(Ser(UCN)), which is less reduced levels than in lymphoblastoid cells in the previous study. Furthermore, approximately 22% reduction in the level of aminoacylation of tRNA(Ser(UCN)) was observed in the mutant cybrid cells. Interestingly, approximately 60-63% decrease of steady-state level of ND6 gene, which belongs to the same precursor as that of tRNA(Ser(UCN)), in cybrid cell lines carrying the A7445G mutation, is more than that observed in lymphoblastoid cells. These observations strongly point out a mechanistic link between the processing defect of the tRNA(Ser(UCN)) precursor and decreased stability of ND6 mRNA precursor. These results also imply the influence of nuclear background on the biochemical phenotype associated with the A7445G mutation.
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PMID:Biochemical characterization of the deafness-associated mitochondrial tRNASer(UCN) A7445G mutation in osteosarcoma cell cybrids. 1569 74

Ifosfamide and methotrexate are widely used for the treatment of pediatric osteosarcoma. However, both these chemotherapeutic drugs can cause encephalopathy. A 17-year-old girl presented with profound hearing loss and dizziness during a postoperative course of ifosfamide, 20 days after a course of methotrexate. Cerebral magnetic resonance imaging (MRI) showed bilateral white matter hypersignal in Fluid Attenuated Inversion Recovery sequences. The clinical evolution was rapidly favorable after methylene blue infusion. This is the second reported case of acute deafness, possibly associated with ifosfamide, whereas MRI data revealed unnoticed chronic methotrexate toxicity. Systematic MRI screening and hearing evaluation may be useful in such cases.
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PMID:Hearing loss during osteosarcoma chemotherapy: when acute ifosfamide toxicity revealed unnoticed methotrexate encephalopathy. 2430