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

The effects of three widely used glutaraldehyde-based fixatives on cellular volume and structure have been studied utilizing TEM, SEM, time-lapse micrography during the fixation procedure, volumetry and demonstration of the lysosomal enzyme acid phosphatase. The cells used were in vitro cultivated human glia and glioma cells and suspensions of isolated rat liver parenchymal cells. The fixatives compared were the following: 2 per cent glutaraldehyde (GA) in 0.1 M Na-cacodylate-HCL buffer (cac) with 0.1 M sucrose (pH 7.2); total osmolality (T) 510 mOsmol; vehicle osmolality (V) 300 mOsm, 2 per cent GA in 0.1 M cac (pH 7.2; T = 410 mOsmol; V = 200 mOsmol) and 1.5 per cent GA in 0.067 M cac with 0.033 M sucrose (pH 7.2; T = 320 mOsmol; V = 170 mOsmol). It was found that the fixative with a vehicle osmolality of 300 mOsmol gave results which were interpreted as ideal while the two fixatives were hypotonic vehicles resulted in changes which were easily demonstrated during volumetry, time-lapse micrography, SEM and cytochemistry. However, the differences observed in the TEM were less obvious and difficult to interpret, the major alternations being changes in the configuration of the ER in the liver cells. In conclusion, our findings show that even small variations in the composition of a glutaraldehyde fixative can result in structural changes which do not correspond to the functional morphology of a living cell. Such changes make correct interpretation of micrographs difficult.
 ...
PMID:A comparison of the effects of three widely used glutaraldehyde fixatives on cellular volume and structure. A TEM, SEM, Volumetric and Cytochemical Study. 40 40

The fine structure of rat gliomas induced transplacentally with a single i.p. dose of 50 mg/kg of Ethylnitrosourea has been studied by using transmission and scanning electron microscope. The subependymal matrix layers of the fetus which was affected by ENU have showed irregular and rough arrangements with expanded extracellular spaces as compared with that of control rats. The cells of subependymal layer seemed to form the microtumor. A so-called "microtumor", which was found in a 8 week old, has been composed of small round cells. The fine structures of these cells have showed the characteristics in primitive oligodendroglioma. The characteristics of the fine structure of astrocytoma cells was identified by both TEM and SEM. The fine structure of subependymal glioma cells was often pleomorphic. These gliomas contained a mixture of primitive oligodendrocytes and ependymal cells together with anaplastic glial cells. With increasing size, the glioma has become more pleomorphic with a mixture of neoplastic oligodendrocytes, astrocytes and ependymal cells, and ependymoma like cells have showed neither cilia nor junctional complex. Abnormal vascular structure in the tumor has been reconfirmed by injection replica scanning electron microscope method. The fine structure of the separated single tumor cell surface was also studied by scanning electron microscope. The differences of the cells surface between that of astrocytoma cell and oligodendroglioma cells were clearly noticed.
 ...
PMID:[Experimental brain tumors produced transplacentally by ethylnitrosourea (IV): ultrastructure studied by using transmission and scanning electron microscope (author's transl)]. 70 10

We have tested the hypothesis that modulated radiofrequency (RF) fields may act as a tumor-promoting agent by altering DNA synthesis, leading to increased cell proliferation. In vitro tissue cultures of transformed and normal rat glial cells were exposed to an 836.55 MHz, packet-modulated RF field at three power densities: 0.09, 0.9, and 9 mW/cm2, resulting in specific absorption rates (SARs) ranging from 0.15 to 59 muW/g. TEM-mode transmission-line cells were powered by a prototype time-domain multiple-access (TDMA) transmitter that conforms to the North American digital cellular telephone standard. One sham and one energized TEM cell were placed in standard incubators maintained at 37 degrees C and 5% CO2. DNA synthesis experiments at 0.59-59 muW/g SAR were performed on log-phase and serum-starved semiquiescent cultures after 24 h exposure. Cell growth at 0.15-15 muW/g SAR was determined by cell counts of log-phase cultures on days 0, 1, 5, 7, 9, 12, and 14 of a 2 week protocol. Results from the DNA synthesis assays differed for the two cell types. Sham-exposed and RF-exposed cultures of primary rat glial cells showed no significant differences for either log-phase or serum-starved condition. C6 glioma cells exposed to RF at 5.9 muW/g SAR (0.9 mW/cm2) exhibited small (20-40%) significant increases in 38% of [3H]thymidine incorporation experiments. Growth curves of sham and RF-exposed cultures showed no differences in either normal or transformed glial cells at any of the power densities tested. Cell doubling times of C6 glioma cells [sham (21.9 +/- 1.4 h) vs. field (22.7 +/- 3.2 h)] also demonstrated no significant differences that could be attributed to altered DNA synthesis rates. Under these conditions, this modulated RF field did not increase cell proliferation of normal or transformed cultures of glial origin.
 ...
PMID:DNA synthesis and cell proliferation in C6 glioma and primary glial cells exposed to a 836.55 MHz modulated radiofrequency field. 909 41

A novel cationic delivery system composed of magnetic aminodextran microspheres (MADM) 1-2 microm in diameter was evaluated along with neutral magnetic dextran microspheres (MDM) for their ability to target intracerebral rat glioma-2 (RG-2) tumors in vivo. The tissue distribution of the microspheres was determined following intraarterial injection (25 mg/kg) over 2 min in male Fisher 344 rats bearing RG-2 tumors as well as normal animals with a magnetic field of 0 or 0.6 T applied to the brain for 30 min. Animals were sacrificed at 30 min or 6 h post-injection after which the microspheres were recovered from various tissues and analyzed for magnetite (Fe3O4) content by atomic absorption. Overall, administration of cationic MADM and neutral MDM particles in normal animals resulted in low brain tissue concentrations with the highest concentrations observed in lung and spleen tissue. In contrast, studies in brain tumor bearing animals resulted in cationic MADM particles concentrating in brain tumor at levels significantly higher than neutral MDM particles (p = 0.0111). Cationic particles were also retained in brain tissue over a longer period of time compared to neutral particles (p = 0.0161) with MADM tumor concentrations decreasing only 4% after 6h compared with a 32% decrease for MDM. Application of a magnetic field failed to produce any significant effect on tissue distribution due to high variability in these groups, but generally resulted in increased brain concentrations and decreased non-target tissue concentrations. TEM analysis of brain tissue sections in tumor animals also revealed differences in particle distribution with MADM particles observed in the interstitial space and MDM particles trapped in the vasculature. In summary, particle charge, state of the vascular endothelium and time significantly influenced particle distribution contributing to the ability of MADM to selectively target brain tumor and supports further investigation of magnetic cationic microspheres as a targeted drug delivery system for brain tumors.
 ...
PMID:Enhanced brain tumor selectivity of cationic magnetic polysaccharide microspheres. 988 8

Small (10-20 nm) uncharged magnetic particles (SMP) were evaluated for their ability to target intracerebral rat glioma-2 (RG-2) tumors in vivo. In an effort to determine the influence of particle size on blood-tumor barrier uptake, the tissue distribution of the injected particles was evaluated following intraarterial injection (4 mg/kg SMP) in male Fisher 344 rats bearing RG-2 tumors with a magnetic field of 0 G or 6000 G applied to the brain for 30 min. Animals were sacrificed at 30 min or 6 h post-injection after which tissues were collected and analyzed for magnetite content. In the presence of a magnetic field, SMP localized in brain tumor tissue at levels of 41-48% dose/g tissue after 30 min and 6 h respectively, significantly greater than non-target tissues. In the absence of a magnetic field only 31-23% dose/g tissue was achieved for the same time points. Tumor targeting of the SMP for brain tumor was demonstrated by large target selectivity indexes (ts) of 2-21 for normal brain tissue, indicating a 2-21 fold increase in concentrations compared to normal brain. In comparison with larger (1 micron) diameter magnetic particles, SMP concentrated in brain tumor at significantly higher levels than magnetic neutral dextran (p = 0.0003) and cationic aminodextran (p = 0.0496) microspheres previously studied. TEM analysis of brain tissue revealed SMP in the interstitial space of tumors, but only in the vasculature of normal brain tissue. These results suggest that changes in the vascular endothelium of tumor tissue promote the selective uptake of SMP and provide a basis for the design of new small drug-loaded particles as targeted drug delivery systems for brain tumors.
 ...
PMID:Distribution of small magnetic particles in brain tumor-bearing rats. 1022 29

Protein transduction domain (PTD) from HIV-1 TAT protein has been reported to translocate across the mammalian cell membrane, also as a part of fusion proteins. However, the true nature of TAT-mediated intercellular spreading is still under debate because it has been claimed to be a fixation artifact. To study the spreading of TAT fusion proteins and their potency to enhance thymidine kinase/ ganciclovir (HSV-TK/GCV) cancer gene therapy, we constructed a novel triple fusion protein containing TAT PTD, HSV-TK and green fluorescent protein (TAT-TK-GFP). This fusion protein has three functional domains in the same polypeptide, allowing reliable determination of the relationship between transduction rate and cell killing efficiency. TAT-TK-GFP was cloned into a lentivirus vector and used for analyses of TAT-mediated protein translocation and enhancement of HSV-TK/GCV cytotoxicity. The triple fusion protein was expressed correctly in vitro, but cell-to-cell translocation was not observed in rat glioma cells (BT4C). However, TAT-TK-GFP made BT4C and SKOV3.ip1 (human ovarian carcinoma) cells significantly more sensitive to ganciclovir than TK-GFP, whereas the effect in PC-3 human prostate carcinoma cells was more subtle. It was also observed that growth in lower serum concentration (2.5-5%) abolished the enhancement in BT4C cells, suggesting that high proliferation rate is one of the factors that contribute to TAT PTD-mediated enhancement of cytotoxicity. In summary, our results indicate that TAT PTD fusion proteins do not translocate intercellularly at detectable levels, but enhancement of the HSV-TK/GCV cytotoxicity can be detected in rat and human tumor cell lines in vitro.
 ...
PMID:HIV-1 TAT protein transduction domain mediates enhancement of enzyme prodrug cancer gene therapy in vitro: a study with TAT-TK-GFP triple fusion construct. 1594 61

Bone marrow-derived cells contribute to tumor angiogenesis. Here, we demonstrate that monocytes expressing the Tie2 receptor (Tie2-expressing monocytes [TEMs]) (1) are a distinct hematopoietic lineage of proangiogenic cells, (2) are selectively recruited to spontaneous and orthotopic tumors, (3) promote angiogenesis in a paracrine manner, and (4) account for most of the proangiogenic activity of myeloid cells in tumors. Remarkably, TEM knockout completely prevented human glioma neovascularization in the mouse brain and induced substantial tumor regression. Besides TEMs and endothelial cells (ECs), Tie2 expression distinguished a rare population of tumor stroma-derived mesenchymal progenitors representing a primary source of tumor pericytes. Therefore, Tie2 expression characterizes three distinct cell types required for tumor neovascularization: ECs, proangiogenic cells of hematopoietic origin, and pericyte precursors of mesenchymal origin.
 ...
PMID:Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. 1616 66

We report the development of a biostable methotrexate-immobilized iron oxide nanoparticle drug carrier that may potentially be used for real-time monitoring of drug delivery through magnetic resonance imaging. Methotrexate (MTX) was immobilized on the nanoparticle surface via a poly(ethylene glycol) self-assembled monolayer (PEG SAM). The cytotoxicity of the nanoparticle-drug conjugate (NP-PEG-MTX) to target cells was studied with 9L glioma cells. Cellular uptake experiments showed that the uptake of NP-PEG-MTX conjugates by glioma cells was considerably higher than that of control nanoparticles. Magnetic resonance imaging in 9L cells cultured with NP-PEG-MTX of various concentrations showed significant contrast enhancement. NP-PEG-MTX demonstrated higher cytotoxicity in 9L cells to free MTX in vitro. Leucovorin, an MTX antidote, was used to rescue the cells that had been exposed to NP-PEG-MTX or free MTX, and the experiment verified the biocompatibility of NP-PEG-MTX conjugates and the MTX on NP-PEG-MTX conjugates to be the true source of the cytotoxicity to the target cells. TEM results showed that NP-PEG-MTX conjugates were internalized into the 9L cellular cytoplasm and retained its crystal structure therein for up to 144 h, as identified by electron diffraction. This prolonged particle retention may allow physicians to image tumor cells exposed to the NP-PEG-MTX conjugate over an extended therapeutic time course.
 ...
PMID:Methotrexate-immobilized poly(ethylene glycol) magnetic nanoparticles for MR imaging and drug delivery. 1719 23

Converging advances in the development of nanoparticle-based imaging probes and improved understanding of the molecular biology of brain tumors offer the potential to provide physicians with new tools for the diagnosis and treatment of these deadly diseases. However, the effectiveness of promising nanoparticle technologies is currently limited by insufficient accumulation of these contrast agents within tumors. Here a biocompatible nanoprobe composed of a poly(ethylene glycol) (PEG) coated iron oxide nanoparticle that is capable of specifically targeting glioma tumors via the surface-bound targeting peptide, chlorotoxin (CTX), is presented. The preferential accumulation of the nanoprobe within gliomas and subsequent magnetic resonance imaging (MRI) contrast enhancement are demonstrated in vitro in 9L cells and in vivo in tumors of a xenograft mouse model. TEM imaging reveals that the nanoprobes are internalized into the cytoplasm of 9L cells and histological analysis of selected tissues indicates that there are no acute toxic effects of these nanoprobes. High targeting specificity and benign biological response establish this nanoprobe as a potential platform to aid in the diagnosis and treatment of gliomas and other tumors of neuroectodermal origin.
 ...
PMID:In vivo MRI detection of gliomas by chlorotoxin-conjugated superparamagnetic nanoprobes. 1823 53

The Met receptor tyrosine kinase is known to be overexpressed in many solid tumors and plays a crucial role in tumor invasive growth and metastasis. In this study, we showed that hepatocyte growth factor-induced Met activation as well as Met-dependent downstream signaling of AKT and p44/42 mitogen-activated protein kinase (MAPK) could be efficiently blocked by TAT-coupled carboxyl-terminal tail peptide of Met receptor (TCTP), and inactivation of Met signaling significantly enhanced the sensitivity of T98G and U251 glioma cells to cis-diaminedichloroplatinum (CDDP, cisplatin). However, neither phosphoinositide 3-kinase/AKT inhibitor LY294002 nor p44/42 MAPK inhibitor PD98059 alone or combined could imitate the effect of TCTP on chemosensitivity enhancement of T98G cells to CDDP, indicating that Met-dependent inactivation of AKT and p44/42 MAPK signaling was not the main cause for the increased chemosensitivity to CDDP. Further studies revealed that TCTP significantly activated p38 MAPK in T98G and U251 cell lines. Activation of p38 MAPK by sorbitol pretreatment resembled the sensitization effects, whereas inhibition of p38 MAPK activation by its inhibitor SB202190 counteracted the sensitization effects induced by TCTP. Therefore, p38 MAPK activation was one of the major causes for the increased chemosensitivity to CDDP induced by Met inactivation. Taken together, the study indicated that Met receptor played an important role in regulating cell response to chemotherapy and suggested that inhibition of Met signaling could be used in combination with other chemotherapeutic regimens in treatment of tumor patients.
 ...
PMID:Inhibition of the met receptor tyrosine kinase signaling enhances the chemosensitivity of glioma cell lines to CDDP through activation of p38 MAPK pathway. 1943 73


1 2 3 4 5 6 7 Next >>