Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The diagnostic value of conventional chest tomography was improved dramatically by filters, manufactured of transparent acrylic glass containing 120 or 240 mu lead aquivalent (DuPont, Neu Isenburg). A perfect compensation of the chest anatomy and pathology in ap-pulmonary tomography can be done easily because the anatomically shaped filters are mobile-mounted in front of the x-ray tube. The position of each filter is visible on the patient's skin. This enables the radiographer to routinely obtain tomograms with diagnostic density values ranging from S = 0.4-2.0. For 6 characteristic areas this was measured in 98%. Such films allow subtle analyses of the tracheal and bronchial wall, the segmental bronchi and pulmonary vessels or pathologic lesion. Compared to cross-sectional imaging CT and MRT, the frontal tomogram shows several aspects of the hilar compartment more clearly because the main central pulmonary structures are located primarily craniocaudally. The conventional tomogram therefore supplies additional views with high spatial resolution. The clinical importance of diagnostic information obtained with ap-tomography using the ATCF are shown in 4 cases. In our hospital, the thoracic surgeon therefore demands conventional tomography with the ATCF to complete staging of benign or malignant chest disease preoperatively.
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PMID:[Conventional section study of thoracic organs. Improved diagnosis with compensation filters of anatomically molded acrylic glass containing lead]. 227 11

We report the development of a reverse transcriptase polymerase chain reaction assay that reliably detects the ETV6-NTRK3 chimeric RNA characteristic of infantile fibrosarcoma and the cellular variant of congenital mesoblastic nephroma (CMN) in formalin-fixed, paraffin-embedded tissue blocks. The 188 base pair polymerase chain reaction fusion product was detected in 11 of 12 cases of cellular CMN from which a larger sized control RNA band could be amplified, and even in 7 of 8 cases in which the control band was not detectable. A variety of other tumors that are in the histologic differential diagnosis of cellular CMN yielded negative results, including four classic CMNs, four rhabdoid tumors of the kidney, and four clear cell sarcomas of the kidney, confirming the assay's specificity. We further demonstrate the assay's utility by illustrating two cases of molecularly confirmed cellular CMN that mimicked rhabdoid tumor and clear cell sarcoma of the kidney. In contrast to previous reports, five mixed CMNs that had both classic and cellular areas all lacked the ETV6-NTRK3 fusion transcript. These results suggest that cases morphologically defined as mixed CMN may represent a mixed group of genetically distinct entities.
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PMID:Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors. 1065 7

We prepared the drug-loaded polymeric nanospheres composed of the methoxy poly(ethylene glycol) (MePEG) and poly(epsilon-caprolactone) (PCL) that showed a narrow size distribution and average diameter of less than 200 nm. We could obtain the nanosphere having a relatively high drug-loading efficiency of about 42% when the feed weight ratio of indomethacin (IMC) to polymer was 1:1. To investigate the IMC pharmacokinetics in the IMC-loaded MePEG/PCL nanosphere (DMEP70) using the rats as animal model, we analyzed the IMC concentration in plasma with HPLC after i.v. bolus administered at a dose of 10 mg/kg in free IMC (control) and IMC-loaded MePEG/PCL nanosphere (DMEP70) groups via tail vein. Pharmacokinetics parameters (mean +/- s.d.) such as the mean residence time (MRT, h), the steady-state volume of distribution (Vdss, l), the terminal half-time (t 1/2, h) and the plasma clearance (CL, l/h) of IMC in each groups (control vs. DMEP70) were determined; MRT (16.97 +/- 4.83 vs. 28.69 +/- 11.28, p < 0.01); Vdss (14.26 +/- 4.86 vs. 20.37 +/- 12.04, p < 0.05); t 1/2 (15.12 +/- 4.77 vs. 23.1 +/- 8.24, p < 0.01); CL (0.84 +/- 0.27 vs. 0.71 +/- 0.41). From these results, we could concluded that MEP70 has a significant potential for sustained release and the enhancement of circulation time of loaded drug by prolonging terminal half-life, increasing MRT and Vdss of IMC. Therefore, The MePEG/PCL block copolymeric nanosphere system is being considered as promising biodegradable and biocompatible drug carrier vehicles for parentral use and may be useful as sustained release injectable delivery systems for hydrophobic drugs.
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PMID:Indomethacin-loaded methoxy poly(ethylene glycol)/ poly(epsilon-caprolactone) diblock copolymeric nanosphere: pharmacokinetic characteristics of indomethacin in the normal Sprague-Dawley rats. 1142 85

Rhabdoid tumor of the thyroid gland is a very rare neoplasm, characterized by significant metastatic potential. All of the 6 cases reported in the recent literature had poor outcomes. We report an additional case involving, to our knowledge, the oldest patient reported so far. A 67-year-old woman had a nodular goiter for all of her adult life and presented with a rapidly growing mass in the right lobe. Histologic examination showed a highly cellular neoplasm with a solid infiltrative growth pattern. Extracapsular invasion was evident. Rhabdoid cells were large, with abundant cytoplasm, eosinophilic inclusions, and eccentric nuclei containing distinct nucleoli. Immunohistochemistry identified vimentin, sarcomeric actin, myoglobin, and cytokeratin expression in the tumor cells; they were negative for desmin, thyroglobulin, and calcitonin. Scattered follicles with nuclear features of papillary thyroid carcinoma were detected; these cells were immunoreactive for thyroglobulin and TTF-1. Reverse transcriptase polymerase chain reaction using specific primers for RET/PTC1 and RET/PTC3 fusion genes identified a RET/PTC3 gene rearrangement in the rhabdoid tumor. Despite radiotherapy, the neoplasm rapidly progressed, with massive local and mediastinal metastasis leading to death 5 months after presentation. The hypothesis that rhabdoid tumor is a variant of anaplastic thyroid carcinoma is supported by the identification of a RET/PTC gene rearrangement, a feature of carcinomas of follicular cell derivation.
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PMID:Rhabdoid tumor of the thyroid gland: a variant of anaplastic carcinoma. 1573 50

The aim of this study was to assess the potential of polymeric micelles to modify the pharmacokinetics and tissue distribution of cyclosporine A (CsA). Drug-loaded methoxy poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-b-PCL) micellar solutions in isotonic medium were prepared and administered intravenously to healthy Sprague-Dawley rats. Blood and tissues were harvested and assayed for CsA, and resultant pharmacokinetic parameters and tissue distribution of CsA in its polymeric micellar formulation were compared to its commercially available intravenous formulation (Sandimmune). In the pharmacokinetic assessment, a 6.1 fold increase in the area under the blood concentration versus time curve (AUC) was observed for CsA when given as polymeric micellar formulation as compared to Sandimmune. The volume of distribution and clearance of CsA as PEO-b-PCL formulation were observed to be 10.0 and 7.6 fold lower, respectively, compared to the commercial formulation. No significant differences in t(1/2) or MRT could be detected. In the biodistribution study, analysis of tissue samples indicated that the mean AUC of CsA in polymeric micelles was lower in liver, spleen and kidney (1.5, 2.1 and 1.4-fold, respectively). Similar to the pharmacokinetic study in these rats, the polymeric micellar formulation gave rise to 5.7 and 4.9-fold increase in the AUC of CsA in blood and plasma, respectively. Our results show that PEO-b-PCL micelles can effectively solubilize CsA, at the same time confining CsA to the blood circulation and restricting its access to tissues such as kidney, perhaps limiting the onset of toxicity.
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PMID:Polymeric micelles for the solubilization and delivery of cyclosporine A: pharmacokinetics and biodistribution. 1600 61

Geldanamycin (GA) and its analogues inhibit heat shock protein 90 (Hsp90) and have shown significant antitumor activity in vivo; however, clinical development of GA has been hampered by its poor solubility and severe hepatotoxicity. More soluble analogues, such as 17-DMAG and 17-AAG, are easier to formulate, and have progressed through early clinical trials. However the large volume of distribution and systemic toxicity associated with these analogues may limit their distribution into tumors, thereby severely reducing efficacy and increasing non-specific toxicities. We have evaluated a formulation of a lipophilic GA prodrug, 17'GAC(16)Br encapsulated in methoxy-capped poly(ethylene glycol)-block-poly(epsilon-caprolactone) (mPEG-b-PCL) micelles, by comparing it to free 17-DMAG at 10 mg/kg in rats. mPEG-b-PCL micelles reported herein demonstrated substantial sustained release and conversion of 17'GAC(16)Br into 17'GAOH at significantly greater levels in all tissues analyzed compared to the free drug, allowing for a 72-fold enhancement in the AUC, a 21-fold decrease in V(d), an 11-fold decrease in CL(tot), and a 2-fold and 7-fold enhancement in the overall MRT of 17'GAC(16)Br and 17'GAOH, respectively. Importantly, the micellar formulation exhibited lower systemic toxicity than 17-DMAG, with a MTD >200 mg/kg and a 2000-fold enhancement in the AUC. 17'GAC(16)Br in micelles were poorly cleared renally, in contrast to 17-DMAG and 17'GAOH, but showed preferential accumulation and prodrug conversion in reticuloendothelial organs of normal animals. Overall, the data indicate that this nanocarrier system is a promising alternative to the current 17-DMAG formulation and offers excellent potential for further pre-clinical and clinical cancer studies.
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PMID:Formulation of a geldanamycin prodrug in mPEG-b-PCL micelles greatly enhances tolerability and pharmacokinetics in rats. 1845 63

Etoposide and nanoparticle formulations were labeled with Tc-99m and their biodistribution and pharmacokinetics were studied after intravenous administration in healthy mice and rabbits respectively. Etoposide was rapidly cleared from the body, while the disposition of nanoparticles was slower. A higher proportion of nanoparticles compared with etoposide was observed in different organs of mice. Scintigraphic images of rabbits concluded that the radioactivity shown by formulations is significantly higher after 4 and 24 h, as compared with etoposide administered in rabbits. AUC(0 - infinity), clearance and MRT are better than those obtained with etoposide administration. The overall high residence of nanoparticles, compared with etoposide, signifies the advantage of PLGA and PCL nanoparticles as drug carriers for etoposide in enhancing the bioavailability and reducing the etoposide-associated toxicity.
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PMID:Etoposide loaded PLGA and PCL nanoparticles II: biodistribution and pharmacokinetics after radiolabeling with Tc-99m. 1876 58

Malignant rhabdoid tumor (MRT) is considered to display multi-phenotypic characteristics but the true origin of this tumor remains unknown. In recent years, the concept of the cancer stem cell (CSC) has drawn great attention. In the present study we investigated six MRT cell lines (TM87-16, STM91-01, TTC642, TTC549, YAM-RTK-1 and TTC1240), for CD133, nestin and Musashi-1 (Msi-1), which are considered to be CSC as well as neural stem cell (NSC) markers, using assays for cell viability and apoptosis, reverse transcriptional polymerase chain reaction (RT-PCR), semi-quantitative PCR and Western blot analysis before and after differentiation-induction with N-(4-hydroxyphenyl) retinamid (4-HPR). Before differentiation-induction with 4-HPR, CD133 was detected in three MRT cell lines, nestin in three cell lines and Msi-1 in five cell lines. In TTC549 after differentiation-induction with 4-HPR, nestin and Msi-1 were down-regulated in a time-dependent manner. Similar down-regulation of Msi-1 was recognized in YAM-RTK-1. In STM91-01, CD133 was gradually down-regulated and Msi-1 was down-regulated after a transient increase. Results from our study indicated that 4-HPR might be effective in some MRTs. Expression of NSC markers showed that some MRTs contain a subpopulation of NSC and down-regulation of NSC markers in MRT cells provides supportive evidence that many MRTs could be considered of neuroectodermal origin.
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PMID:Expression of neural stem cell markers in malignant rhabdoid tumor cell lines. 2004 11

The objective of this study was to prepare a novel mifepristone-loaded PCL/Pluronic F68 implant to achieve long-term treatment of endometriosis. PCL/Pluronic F68 compound (90/10, w/w) with viscosity average molecular weight of 65,000 was successfully synthesized. The end-capped Pluronic F68 was incorporated in PCL matrixes as molecular dispersion without forming a copolymer. The mifepristone-loaded implant made of PCL/Pluronic F68 compound was a cylindrical capsule with an outer diameter of 2.5mm and an inner diameter of 2.2mm. The surface of PCL/Pluronic F68 compound appears porous because Pluronic F68 which is water soluble could leach out due to the water phase. Drug loading of 0.75-, 1.5- and 3.0-cm length implants was 3.05+/-0.18, 6.06+/-0.41 and 11.87+/-0.39mg, respectively. A sustained mifepristone release rate without obvious initial burst and later decline over a period of 180d was observed. The cumulative drug release showed a linear relationship with time, indicating that mifepristone release from the implants followed zero-order kinetics (R(2)>0.99). The data showed that the C(max) and AUC(0-inf) were proportional to imlant length and dose, and all groups reached plasma C(max) at about the same time (approximately 7d) and had similar T(1/2) (approximately 150d) and MRT (approximately 220d). There were obvious inhibitory effects on the growth of endometrial explants in Wister rats in a dose-dependent manner after administration of mifepristone-loaded implants with implant length from 1.5 to 9.0cm for 1-3 months. However, mifepristone-loaded implants with implant length of 12.0cm had no better inhibitory effects on the growth of endometrium when compared with the implants with implant length of 9.0cm (P>0.05). In conclusion, subcutaneous implantation of mifepristone-loaded PCL/Pluronic F68 capsules was proven an effective means for long-term treatment of chronic endometriosis.
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PMID:A novel mifepristone-loaded implant for long-term treatment of endometriosis: in vitro and in vivo studies. 2013 84

As our understanding of pediatric brain neoplasia flourishes, so does the development of diagnostic, prognostic, and predictive biomarkers. The neuropathologist uniquely stands at the crossroads between pathology and molecular genetics, often overseeing the creation, development, implementation, delivery, and reporting of the newest bioassays. This review serves to highlight the key microscopic and genetic features of the most common pediatric brain tumors. For example, INI-1 immunohistochemistry has assisted in identifying several previously unrecognized cases of rhabdoid cell-poor atypical teratoid rhabdoid tumor (ATRT). The latest discovery involving the tandem duplication and fusion BRAF-KIAA1549 on chromosome 7q34 in pilocytic astrocytoma has drawn attention to the MAPK-ERK pathway and its potential chemotherapeutic manipulation. The newly identified IDH1 mutation, which appears characteristic of "secondary astrocytomas," has yet to be studied in the pediatric population, but some researchers have extolled concomitant BRAF-KIAA1549/IDH1 analysis in the neuropathologic workup of many astrocytomas. Through these and other advances, our understanding of pediatric brain tumors will continue to expand exponentially, and as such will set the stage for truly effectual future treatments.
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PMID:Pediatric brain tumors: a histologic and genetic update on commonly encountered entities. 2091 7


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