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)

Telomerase, a ribonucleoprotein enzyme, maintains telomere length and is expressed by the majority of malignant tumours, but not in normal tissue. Telomerase facilitates the division of tumour cells and its activity has been suggested as a prognostic indicator, but so far the regulation or modulation of telomerase activity has not been described. Hyperthermia has been shown to decrease tumour growth by inhibition of proliferation. Therefore, the effect of hyperthermia on telomerase activity in human osteosarcoma cells was studied. Telomerase activity was measured by the Telomeric Repeat Amplification Protocol (TRAP) assay in three different osteosarcoma cell lines subjected to hyperthermia (42.5 degrees C, 90 min) and in controls cultured under basal conditions (37 degrees C). Telomerase activity was strongly inhibited by hyperthermia and decreased in all cell lines tested after a recovery time of 2 h under basal conditions (37 degrees C) to an activity of approximately 85%, after 12 h approximately 60% and with lowest activity approximately 55% compared to activity of control cells. Telomerase activity then increased and reached the same, i.e. basal, level as before hyperthermia, after 112 h. These results show that hyperthermia results in a reversible downregulation of telomerase activity in osteosarcoma cells. This effect facilities studies on the regulation of telomerase activity and detailed information might lead to new therapeutic strategies.
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PMID:Reversible downregulation of telomerase activity by hyperthermia in osteosarcoma cells. 1100 78

Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. Telomerase activity was observed and correlated with aggressiveness in different neoplasms such as breast, prostate, blood and brain cancers, among others. To investigate whether telomerase activity is an index of aggressiveness in bone and soft tissue lesions of the extremities, 66 biopsy samples from our tissue bank were studied. These samples included 43 high-grade sarcomas, 9 aggressive benign tumors and 14 totally benign lesions. The samples were collected from patients homogeneously treated at the Rizzoli Orthopaedic Institute with a follow-up ranging from 4 to 11 years (median, 7 years). A non-radioactive polymerase chain reaction-based enzyme-linked immunosorbent assay was used for the study. All tumors investigated were positive for telomerase activity. Among benign lesions, only 2 aneurysmal bone cysts showed higher telomerase activity than the cut-off point, whereas all the other benign lesions had lower activity. Our results indicate that high levels of telomerase activity in bone and soft tissue lesions correlate with more aggressive clinical behavior in patients treated with surgery alone. An interesting inverse correlation between telomerase activity and occurrence of pulmonary metastasis was detected in osteosarcoma patients treated with chemotherapy. A parallel increase of telomerase activity and malignancy was observed in the adipose and cartilagineous tissue lesions. Our data suggest that telomerase activity could be considered a marker of tumor aggressiveness for bone and soft tissue lesions. The results obtained in osteosarcoma samples suggest that low levels of telomerase activity may be predictive of the prognosis and should influence the therapeutic protocol.
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PMID:Presence of telomerase activity in different musculoskeletal tumor histotypes and correlation with aggressiveness. 1130 48

There is now compelling evidence that messenger ribonucleoprotein (mRNP) complexes after the release from the transcription/processing sites execute essentially unhindered Brownian movements in the nucleoplasm and target nuclear pore complexes (NPCs) by chance encounter. For the majority of genes expressed in eukaryotic cells, only single/few transcript copies are generated, which reinforces the stochastic nature of NPC localization. In this paper, I analyse the NPC localization by freely diffusing single mRNPs and discuss the implications for the temporal progression of gene expression and consecutive processes associated with the gene products. To this end, a walk-and-capture model is considered, assuming a spherical nuclear compartment with a partially absorbing boundary. Perfect absorption and perfect reflection mark the extreme outcomes. For this model, the closed-form analytic solution of the first-passage time probability density function (FPT p.d.f.), the mean passage time and variance have been obtained. The FPT p.d.f. enables to calculate the probability that single mRNPs localize the nuclear boundary and dock to NPCs within certain time windows. For freely moving mRNP complexes in osteosarcoma cell nuclei, a mean apparent diffusion coefficient (D) of 0.04 microm2 s(-1) (range 0.01-0.09 microm2 s(-1)) has been reported. Assuming a nuclear radius of 8 microm and D=0.04 microm2 s(-1), the position-averaged minimum mean passage time <tau(r0)>min for the considered model is 1.8 min, which presupposes perfect absorption of the mRNP complex at the first encounter with the nuclear boundary. In this case, the probability of capture in the time interval (0, <tau(r0)>min) is 0.67. In smaller sized yeast cell nuclei with a radius of 0.8 mum and D=0.04 microm2 s(-1), single diffusing mRNPs would localize an NPC within tens of seconds, rather than minutes.
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PMID:Temporal fluctuation of nuclear pore complex localization by single diffusing mRNP complexes. 1591 55

Human YVH1 (hYVH1), also known as dual specificity phosphatase 12 (DUSP12), is a poorly characterized atypical dual specificity phosphatase widely conserved throughout evolution. Recent findings have demonstrated that hYVH1 expression affects cellular DNA content and is a novel cell survival phosphatase preventing both thermal and oxidative stress-induced cell death, whereas studies in yeast have established YVH1 as a novel 60S ribosome biogenesis factor. In this study, we have isolated novel hYVH1-associating proteins from human U2OS osteosarcoma cells using affinity chromatography coupled to mass spectrometry employing ion mobility separation. Numerous ribosomal proteins were identified, confirming the work done in yeast. Furthermore, proteins known to be present on additional RNP particles were identified, including Y box-binding protein 1 (YB-1) and fragile X mental retardation protein, proteins that function in translational repression and stress granule regulation. Follow-up studies demonstrated that hYVH1 co-localizes with YB-1 and fragile X mental retardation protein on stress granules in response to arsenic treatment. Interestingly, hYVH1-positive stress granules were significantly smaller, whereas knocking down hYVH1 expression attenuated stress granule breakdown during recovery from arsenite stress, indicating a possible role for hYVH1 in stress granule disassembly. These results propagate a role for dual specificity phosphatases at RNP particles and suggest that hYVH1 may affect a variety of fundamental cellular processes by regulating messenger ribonucleoprotein (mRNP) dynamics.
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PMID:The Atypical Dual Specificity Phosphatase hYVH1 Associates with Multiple Ribonucleoprotein Particles. 2785 39