Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([18F]FHPG, 2) has been synthesized by nucleophilic substitution of N(2)-(p-anisyldiphenylmethyl)-9-[[1-(p-anisyldiphenylmethoxy)-3-toluenesulfonyloxy-2-propoxy]methyl]guanine (1) with potassium [18F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 degrees C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 degrees C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 degrees C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 degrees C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126 +/- 0.022, n=5 and 0.165 +/- 0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ( approximately 5-30 microg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains approximately 10-25 microg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is readily amenable for automation.
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PMID:A simplified one-pot synthesis of 9-[(3-[18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy. 1157 10

We hereby report the synthesis of four fluorine-18 labeled tyrosine derivatives, 3-(2-[(18)F]fluoroethyl)tyrosine ([(18)F]1, [(18)F]ortho-FET), 3-(3-[(18)F]fluoropropyl)tyrosine ([(18)F]2, [(18)F]ortho-FPT) O-methyl-[3-(2-[(18)F]fluoroethyl)]tyrosine ([(18)F]3, [(18)F]MFET), and O-methyl-[3-(3-[(18)F]fluoropropyl)]tyrosine ([(18)F]4, [(18)F]MFPT). The fluorine-18 labeled tyrosine derivatives were prepared by the displacement reaction of the ethyl and propyl tosylates with K[(18)F]/K2.2.2 in acetonitrile under no-carrier-added (NCA) conditions, followed by hydrolysis with 4N HCl. The biological properties of labeled compounds were evaluated in rats bearing 9L tumor after an intravenous injection and PET image was obtained. The tumor/blood and tumor/brain ratios were 2.06, 2.92 for [(18)F]1, 2.25, 4.05 for [(18)F]2, 2.88, 1.90 for [(18)F]3, and 2.00, 2.60 for [(18)F]4 at 60 min post injection, respectively. The PET image showed localized accumulation of PET tracers in 9L glioma of the rat.
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PMID:Syntheses of F-18 labeled fluoroalkyltyrosine derivatives and their biological evaluation in rat bearing 9L tumor. 1703 15

Poly(d,l-lactic-co-glycolic acid) (PLGA) polymers having different average molecular weights were chemically conjugated to two imidazopyridinacetamides (1 and 2), chosen as model Peripheral Benzodiazepine Receptor (PBR) ligands, via an ester or amide linkage. It is in order to evaluate these conjugates as delivery systems of PBR ligands endowed with apoptosis inducing activity. Various coupling reaction conditions were tested to optimize the conjugation process. After purification by extensive dialysis procedures, the macromolecular conjugates were characterized by FT-IR, UV, (1)H NMR spectroscopy, DSC and the average molecular weights of synthesized conjugates were determined by GPC. PBR ligand released from these conjugates occurred in human serum and in 0.1 N HCl solution at a faster rate than that observed in phosphate buffer, pH 7.4. Moreover, the macromolecular conjugates displayed high affinity and selectivity for PBR. Cytotoxicity studies demonstrated that PBR ligand-PLGA polymer conjugates induce survival inhibition in rat C6 glioma cell line. Fluorescence microscopy studies evidenced the cellular uptake of FITC-conjugated probes 10 and 11 and moreover, the mitochondrial morphology modification induced by compounds 1 and 4a. Therefore, this study demonstrates that this PBR ligand-PLGA combination may provide a new mitochondrial targeted approach useful for improved cancer chemotherapy.
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PMID:Peripheral benzodiazepine receptor ligand-PLGA polymer conjugates potentially useful as delivery systems of apoptotic agents. 1937 31

The delivery of genes or viruses via liposomes is a common approach used to enhance delivery efficiency. In the current study, to enhance delivery efficiency, proteoliposomes (PLs) containing adenovirus (Ad) were synthesized with dimyristoylphosphatidylcholine (DMPC), cholesterol, and apolipoprotein A-I (apoA-I). Wildtype apoA-I (WT) or V156K-apoA-I (V156K) was then used as an apolipoprotein to compare the structural and functional differences of the PLs. The particle diameter of V156K-PL-Ad was slightly larger than that of WT-PL-Ad, based on native gel electrophoresis. V156K showed more rapid phospholipid bilayer formation than did the WT, based on DMPC clearance. In addition, V156K exhibited maximal fluorescence that was more blue than that of WT in the PL state. Moreover, isothermal denaturation in response to the addition of guanidine hydrochloride (Gnd-HCl) revealed that V156K was more resistant, with no denaturation until 3 M Gnd-HCl was added. In addition, electron microscopy revealed that the viral particles were well associated with PL particles, which had a discoidal structure and were shaped like rouleaux. In addition, treatment of Ad in the PL state showed enhanced green fluorescent protein (GFP) expression when compared with treatment with Ad alone or with DMPC-Ad in hepatoma and brain glioma cells. Cells treated with WT-PL-Ad and V156K-PL-Ad showed approximately 50% more GFP expression than cells treated with Ad alone or with DMPC-Ad after 24 hr of incubation at 37 degrees C, indicating that viral stability was highly increased in the PL state. Furthermore, V156K-PL-Ad showed the highest expression of GFP in adult zebrafish (9 weeks old) at 5 days postinjection (10.5- and 3.8-fold more GFP expressed than by Ad only and DMPC-Ad, respectively). In conclusion, the efficiency of viral delivery and the stability of the virus were significantly enhanced when PLs containing apoA-I were used in cellular and zebrafish models.
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PMID:Enhanced delivery of adenovirus, using proteoliposomes containing wildtype or V156K apolipoprotein A-I and dimyristoylphosphatidylcholine. 2003 14

Effectiveness of CNS-acting drugs depends on the localization, targeting, and capacity to be transported through the blood-brain barrier (BBB) which can be achieved by designing brain-targeting delivery vectors. Hence, the objective of this study was to screen the formulation and process variables affecting the performance of sertraline (Ser-HCl)-loaded pegylated and glycosylated liposomes. The prepared vectors were characterized for Ser-HCl entrapment, size, surface charge, release behavior, and in vitro transport through the BBB. Furthermore, the compatibility among liposomal components was assessed using SEM, FTIR, and DSC analysis. Through a thorough screening study, enhancement of Ser-HCl entrapment, nanosized liposomes with low skewness, maximized stability, and controlled drug leakage were attained. The solid-state characterization revealed remarkable interaction between Ser-HCl and the charging agent to determine drug entrapment and leakage. Moreover, results of liposomal transport through mouse brain endothelialpolyoma cells demonstrated greater capacity of the proposed glycosylated liposomes to target the cerebellar due to its higher density of GLUT1 and higher glucose utilization. This transport capacity was confirmed by the inhibiting action of both cytochalasin B and phenobarbital. Using C6 glioma cells model, flow cytometry, time-lapse live cell imaging, and in vivo NIR fluorescence imaging demonstrated that optimized glycosylated liposomes can be transported through the BBB by classical endocytosis, as well as by specific transcytosis. In conclusion, the current study proposed a thorough screening of important formulation and process variabilities affecting brain-targeting liposomes for further scale-up processes.
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PMID:Glycosylated Sertraline-Loaded Liposomes for Brain Targeting: QbD Study of Formulation Variabilities and Brain Transport. 2678 80

Circular RNAs belong to a new category of non-coding RNAs, characterised by a circular structure, conservation, stability and high expression in eukaryotes. They often show tissue- or cell-specific expression. Here, we identified a testis-enriched circular RNA (circRNA), circular Bbs9 (circ-Bbs9) that is highly expressed in mouse testis. An RNase R treatment experiment confirmed that circ-Bbs9 is indeed a circRNA. In situ hybridisation experiments showed that circ-Bbs9 is expressed in Leydig cells along seminiferous tubules and in the cytoplasm of the TM3 Leydig cell line. Knocking down the circ-Bbs9 in TM3 cells by lentivirus vectors arrested cell proliferation, whereas overexpression of circ-Bbs9 induced cell proliferation significantly. Knocking down circ-Bbs9 inhibited the protein level of cyclin D2 (Ccnd2) and RNA immunoprecipitation results showed that circ-Bbs9 interacts with Ccnd2. Our results show that use of the Hedgehog pathway Smoothened Agonist (SAG) HCl and antagonists cyclopamine and gant6 affects the expression levels of Glioma-Associated Oncogene Homolog 1 (Gli1), Ccnd2 and other genes in this pathway. Our research reveals that a Leydig cell-specific circRNA, circ-Bbs9, plays a critical role in Leydig cell proliferation through regulating the levels of cell cycle-related Ccnd2. Thus, our results emphasise the important role of circRNA in the male reproductive system.
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PMID:Testis-enriched circular RNA circ-Bbs9 plays an important role in Leydig cell proliferation by regulating a CyclinD2-dependent pathway. 3170 14


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