The effects of dexamethasone on C6 astrocytoma radiosensitivity

1989 ◽  
Vol 70 (5) ◽  
pp. 767-773 ◽  
Author(s):  
Carl D. Lordo ◽  
Eric C. Stroude ◽  
Rolando F. Del Maestro
Keyword(s):  
Three Dimensional ◽  
Inhibitory Effect ◽  
Plating Efficiency ◽  
Dexamethasone Treatment ◽  
Content Type ◽  
Astrocytoma Cells ◽  
C6 Astrocytoma ◽  
Radiation Induced ◽  
Fine Print

✓ Brain-tumor patients often undergo radiation therapy while receiving corticosteroids for the treatment of cerebral edema. Studies have demonstrated that dexamethasone is radioprotective in a number of cell lines. The C6 astrocytoma cell line is well established in vitro and is modulated by dexamethasone treatment. It has therefore been hypothesized that dexamethasone-treated C6 astrocytoma cells would be more resistant to radiation-induced damage. The present study was carried out to assess this hypothesis using both the in vitro C6 astrocytoma monolayer and three-dimensional multicellular spheroid models. Dexamethasone was inhibitory to the C6 astrocytoma cells in the monolayer preparation, increasing their doubling time by 13%. In the spheroid cultures, dexamethasone treatment decreased the number of cells per spheroid by 46%. Dexamethasone did not affect the plating efficiency of either the cells from the monolayer experiment or those dissociated from spheroids, however, suggesting that the inhibitory effect was not tumoricidal. At a clinical concentration (1.94 × 10−5 M), dexamethasone did not significantly influence plating efficiency of irradiated C6 astrocytoma cells in monolayer or three-dimensional spheroid cultures.

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

Serum proteolytic activity during the growth of C6 astrocytoma

1992 ◽  
Vol 77 (4) ◽  
pp. 595-600 ◽  
Author(s):  
Indrasen S. Vaithilingam ◽  
Warren McDonald ◽  
Noel K. Brown ◽  
Eric Stroude ◽  
Robert A. Cook ◽  
...  
Keyword(s):  
Proteolytic Activity ◽  
Type Iv Collagen ◽  
Collagenase Activity ◽  
Type Iv Collagenase ◽  
Content Type ◽  
Type Iv ◽  
Astrocytoma Cells ◽  
Vessel Remodeling ◽  
C6 Astrocytoma ◽  
Fine Print

✓ Tumor growth is dependent on the ability of neoplastic cells to induce angiogenesis. Blood-vessel remodeling requires the reconstruction of the nonfibrous proteins and type IV collagen components of the basement membrane. This study has assessed the influence of the growth of C6 astrocytoma cells in the rat spheroid implantation model on serum general protease and type IV collagenase activity. The results demonstrate that general protease activity increased in serum, reaching maximum values on Day 6 and Day 13 following spheroid implantation, and that type IV collagenase activity increased in serum, obtaining maximum values on Day 8 and Day 15. The measurement of serum proteolytic activity may be of value in the detection of recurrent tumors.

Antiproliferative effect of trapidil, a platelet-derived growth factor antagonist, on a glioma cell line in vitro

1990 ◽  
Vol 73 (3) ◽  
pp. 436-440 ◽  
Author(s):  
Jun-ichi Kuratsu ◽  
Yukitaka Ushio
Keyword(s):  
Growth Factor ◽  
Cell Lines ◽  
Glioma Cell ◽  
Glioma Cells ◽  
Inhibitory Effect ◽  
Platelet Derived Growth Factor ◽  
Content Type ◽  
Glioma Cell Lines ◽  
Fine Print

✓ Platelet-derived growth factor (PDGF) is produced by glioma cells. However, there is heterogeneity among glioma cell lines in the production of PDGF. It has been demonstrated that U251MG cells produce a PDGF-like molecule while U105MG cells do not. Trapidil, a specific antagonist of PDGF, competes for receptor binding with PDGF. Therefore, the inhibitory effect of trapidil on the proliferation of glioma cells was investigated in vitro using two glioma cell lines. At 100 µg/ml, trapidil significantly inhibited the proliferation of U251MG cells (which produce the PDGF-like molecule). At the same trapidil concentration, the proliferation of U105MG cells (which do not produce the PDGF-like molecule) was not inhibited. The inhibitory effect of trapidil was remarkable on Days 3 and 4 of culture. After 4 days of incubation, the proliferation of U251MG cells was 46% of the control preparation. Trapidil enhanced the antitumor effect of 3-((4-amino-2-methyl-5-pyrimidinyl)ethyl)-1-(2-chloroethyl)-1-nitro-sourea (ACNU) against U251MG cells. The enhancing effect was highest on Days 4 and 6 of culture. After 6 days of incubation in the presence of 100 µg/ml trapidil and 1 µg/ml ACNU, the proliferation of U251MG cells was 18% of the control preparation. These findings suggest that trapidil interrupts the autocrine loop at the PDGF and PDGF-receptor level and that combination therapy with trapidil and ACNU may be useful in the treatment of glioma.

Effects of clotrimazole on the growth, morphological characteristics, and cisplatin sensitivity of human glioblastoma cells in vitro

1999 ◽  
Vol 90 (5) ◽  
pp. 918-927 ◽  
Author(s):  
M. Humayun Khalid ◽  
Shobu Shibata ◽  
Tsuyoshi Hiura
Keyword(s):  
P53 Gene ◽  
Inhibitory Effect ◽  
Wild Type ◽  
Glioblastoma Cells ◽  
Content Type ◽  
Growth Inhibitory ◽  
Wild Type P53 ◽  
Fine Print ◽  
In Cells

Object. Clotrimazole, an antimycotic drug, inhibits proliferation of normal and cancer cells by downregulating the movement of intracellular Ca++ and K+. The authors examined the effect of clotrimazole on the growth and sensitivity to cisplatin of two human glioblastoma cell lines—A172, which has the wild-type p53 gene, and T98G, which has the mutant p53 gene in vitro.Methods. The A172 and T98G glioblastoma cells were exposed to clotrimazole and cell growth was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium chloride colorimetric assay. Clotrimazole produced a dose-dependent inhibition of cell proliferation and caused changes in cellular structure toward a well-differentiated form. The growth inhibitory effect of clotrimazole was reversible. Western immunoblot analysis revealed a marked increase in cellular glial fibrillary acidic protein and wild-type p53 and a decrease in c-myc and c-fos oncoproteins in both cell lines treated with clotrimazole. Flow cytometric analysis revealed that clotrimazole-treated cells accumulated in the G0/G1 phase with a marked decrease in cells in the S phase; when clotrimazole was washed out from the culture medium, cells again started to proliferate, with a marked decrease in cells in the G0/G1 phase and an increase in cells in the S phase. The growth inhibitory effect of clotrimazole could not be overcome by exogenous stimulation with either epidermal growth factor or c-myc peptide. A combined treatment with clotrimazole and cisplatin significantly enhanced cell cytotoxicity compared with treatment using either drug alone. A DNA fragmentation assay showed that both clotrimazole and cisplatin induced apoptosis, which was increased in cells treated by both drugs.Conclusions. The present study indicates that clotrimazole inhibits cell proliferation accompanied by morphological changes toward differentiation of glioblastoma cells and that this drug synergistically enhances the antitumor effect of cisplatin by inducing wild-type p53—mediated apoptosis.

Stereotactic radiosurgery versus stereotactic radiotherapy for patients with vestibular schwannoma: a Leksell Gamma Knife Society 2000 debate

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 90-92 ◽  
Author(s):  
Mark E. Linskey
Keyword(s):  
Gamma Knife ◽  
Stereotactic Radiotherapy ◽  
Three Dimensional ◽  
Late Recurrence ◽  
Vestibular Schwannomas ◽  
Tumor Control ◽  
Complication Rates ◽  
Content Type ◽  
Single Fraction ◽  
Fine Print

✓ By definition, the term “radiosurgery” refers to the delivery of a therapeutic radiation dose in a single fraction, not simply the use of stereotaxy. Multiple-fraction delivery is better termed “stereotactic radiotherapy.” There are compelling radiobiological principles supporting the biological superiority of single-fraction radiation for achieving an optimal therapeutic response for the slowly proliferating, late-responding, tissue of a schwannoma. It is axiomatic that complication avoidance requires precise three-dimensional conformality between treatment and tumor volumes. This degree of conformality can only be achieved through complex multiisocenter planning. Alternative radiosurgery devices are generally limited to delivering one to four isocenters in a single treatment session. Although they can reproduce dose plans similar in conformality to early gamma knife dose plans by using a similar number of isocenters, they cannot reproduce the conformality of modern gamma knife plans based on magnetic resonance image—targeted localization and five to 30 isocenters. A disturbing trend is developing in which institutions without nongamma knife radiosurgery (GKS) centers are championing and/or shifting to hypofractionated stereotactic radiotherapy for vestibular schwannomas. This trend appears to be driven by a desire to reduce complication rates to compete with modern GKS results by using complex multiisocenter planning. Aggressive advertising and marketing from some of these centers even paradoxically suggests biological superiority of hypofractionation approaches over single-dose radiosurgery for vestibular schwannomas. At the same time these centers continue to use the term radiosurgery to describe their hypofractionated radiotherapy approach in an apparent effort to benefit from a GKS “halo effect.” It must be reemphasized that as neurosurgeons our primary duty is to achieve permanent tumor control for our patients and not to eliminate complications at the expense of potential late recurrence. The answer to minimizing complications while maintaining maximum tumor control is improved conformality of radiosurgery dose planning and not resorting to homeopathic radiosurgery doses or hypofractionation radiotherapy schemes.

Release of collagen type IV degrading activity from C6 astrocytoma cells and cell density

1996 ◽  
Vol 84 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
Masashi Tamaki ◽  
Warren McDonald ◽  
Rolando F. Del Maestro
Keyword(s):  
Cell Density ◽  
Collagen Type ◽  
Cell Communication ◽  
Collagen Type Iv ◽  
Major Protein ◽  
Content Type ◽  
Type Iv ◽  
Astrocytoma Cells ◽  
C6 Astrocytoma

✓ Type IV collagen is a major protein component of the vascular basement membrane and its degradation is crucial to the initiation of tumor-associated angiogenesis. The authors have investigated the influence of cell density on the release of collagen type IV degrading activity by C6 astrocytoma cells in monolayer culture. The release of collagen type IV degrading activity was assessed biochemically, immunocytochemically, and by Western blot analysis. The results demonstrate that increasing plating density and increasing cell density are associated with decreased collagen type IV degrading activity released per tumor cell. These findings indicate the existence of regulatory mechanisms dependent on cell—cell communication, which modulate release of collagen type IV degrading activity. The extrapolation of these results to the in vivo tumor microenvironment would suggest that individual and/or small groups of invading tumor cells, distant from the main tumor mass, would release substantial collagen type IV degrading activity, which may be crucial to their continued invasion and to angiogenesis.

Biomechanical characteristics of C1–2 cable fixations

1996 ◽  
Vol 85 (2) ◽  
pp. 316-322 ◽  
Author(s):  
Curtis A. Dickman ◽  
Neil R. Crawford ◽  
Christopher G. Paramore
Keyword(s):  
Cyclic Loading ◽  
Translational Motion ◽  
Biomechanical Testing ◽  
Three Dimensional ◽  
Constrained Motion ◽  
Content Type ◽  
Physiological Range ◽  
Fixation Techniques ◽  
Cable Fixation ◽  
Fine Print

✓ The biomechanical characteristics of four different methods of C1–2 cable fixation were studied to assess the effectiveness of each technique in restoring atlantoaxial stability. Biomechanical testing was performed on the upper cervical spines of four human cadaveric specimens. Physiological range loading was applied to the atlantoaxial specimens and three-dimensional motion was analyzed with stereophotogrammetry. The load–deformation relationships and kinematics were measured, including the stiffness, the angular ranges of motion, the linear ranges of motion, and the axes of rotation. Specimens were nondestructively tested in the intact state, after surgical destabilization, and after each of four different methods of cable fixation. Cable fixation techniques included the interspinous technique, the Brooks technique, and two variants of the Gallie technique. All specimens were tested immediately after fixation and again after the specimen was fatigued with 6000 cycles of physiological range torsional loading. All four cable fixation methods were moderately flexible immediately; the different cable fixations allowed between 5° and 40° of rotational motion and between 0.6 and 7 mm of translational motion to occur at C1–2. The Brooks and interspinous methods controlled C1–2 motion significantly better than both of the Gallie techniques. The motion allowed by one of the Gallie techniques did not differ significantly from the motion of the unfixed destabilized specimens. All cable fixation techniques loosened after cyclic loading and demonstrated significant increases in C1–2 rotational and translational motions. The bone grafts shifted during cyclic loading, which reduced the effectiveness of the fixation. The locations of the axes of rotation, which were unconstrained and mobile in the destabilized specimens, became altered with cable fixation. The C1–2 cables constrained motion by shifting the axes of rotation so that C-1 rotated around the fixed cable and graft site. After the specimen was fatigued, the axes of rotation became more widely dispersed but were usually still localized near the cable and graft site. Adequate healing requires satisfactory control of C1–2 motion. Therefore, some adjunctive fixation is advocated to supplement the control of motion after C1–2 cable fixation (that is, a cervical collar, a halo brace, or rigid internal fixation with transarticular screws).

Antitumor effects of antiprogesterones on human meningioma cells in vitro and in vivo

1994 ◽  
Vol 80 (3) ◽  
pp. 527-534 ◽  
Author(s):  
Yasuhiro Matsuda ◽  
Keiichi Kawamoto ◽  
Katsuzo Kiya ◽  
Kaoru Kurisu ◽  
Kazuhiko Sugiyama ◽  
...  
Keyword(s):  
Marked Reduction ◽  
Tumor Volume ◽  
Collagen Gel ◽  
Antitumor Effects ◽  
Histological Changes ◽  
Content Type ◽  
The Relationship ◽  
Fine Print

✓ The presence of the progesterone receptor (PR) in meningioma tissue has been confirmed by previous investigations. Studies have shown that the antiprogesterone drug, mifepristone, is a potent agent that inhibits the growth of cultured meningioma cells and reduces the size of meningiomas in experimental animal models and humans. However, these studies have not fully examined the relationship between the antitumor effects of an antiprogesterone agent and the expression of the PR. The present study examined the antitumor effects of mifepristone and a new potent antiprogesterone agent, onapristone; a correlation between the antitumor effects of these antiprogesterones and the presence of PR's in meningiomas in vitro and in vivo was also investigated. Meningioma tissue surgically removed from 13 patients was used in this study. In the in vitro arm of the study, mifepristone and onapristone exhibited cytostatic and cytocidal effects against cultured meningioma cells, regardless of the presence or absence of PR's; however, three PR-negative meningiomas showed no response to any dose of mifepristone and/or onapristone. In the in vivo arm, meningioma cells, embedded in a collagen gel, were implanted into the renal capsules of nude mice. Antiprogesterone treatment resulted in a marked reduction of the tumor volume regardless of the presence or absence of PR's. No histological changes in the meningioma cells suggestive of necrosis or apoptosis were detected in any of the mice treated with antiprogesterones. These findings suggest that mifepristone and onapristone have an antitumor effect against meningioma cells via the PR's and/or another receptor, such as the glucocorticoid receptor.

Intraoperative angiography in the resection of arteriovenous malformations

1994 ◽  
Vol 80 (1) ◽  
pp. 73-78 ◽  
Author(s):  
Shigetaka Anegawa ◽  
Takashi Hayashi ◽  
Ryuichiro Torigoe ◽  
Katsuhiko Harada ◽  
Shun-ichi Kihara
Keyword(s):  
Surgical Resection ◽  
Arteriovenous Malformations ◽  
Three Dimensional ◽  
Initial Operation ◽  
Total Resection ◽  
Intraoperative Angiography ◽  
Content Type ◽  
Fine Print

✓ Surgical resection of 13 operatively obscure arteriovenous malformations (AVM's) was accomplished with the assistance of intraoperative angiography, which was performed stereographically to provide three-dimensional orientation and was repeated until total resection of the AVM was confirmed. All films obtained were subtracted to improve clarity. The method presented here may be useful for the resection of all types of AVM. Only two patients had residual AVM after the initial operation. No complications attributable to angiography were noted.

Neoplastic and pharmacological influence on the permeability of an in vitro blood-brain barrier

1995 ◽  
Vol 82 (6) ◽  
pp. 1053-1058 ◽  
Author(s):  
Paul A. Grabb ◽  
Mark R. Gilbert
Keyword(s):  
Endothelial Cell ◽  
Rat Brain ◽  
Phospholipase A ◽  
Cell Permeability ◽  
Capillary Endothelium ◽  
Brain Capillary ◽  
Content Type ◽  
Endothelial Cell Permeability ◽  
Fine Print

✓ The authors investigated the effects of glioma cells and pharmacological agents on the permeability of an in vitro blood-brain barrier (BBB) to determine the following: 1) whether malignant glia increase endothelial cell permeability; 2) how glucocorticoids affect endothelial cell permeability in the presence and absence of malignant glia; and 3) whether inhibiting phospholipase A2, the enzyme that releases arachidonic acid from membrane phospholipids, would reduce any malignant glioma—induced increase in endothelial cell permeability. Primary cultures of rat brain capillary endothelium were grown on porous membranes; below the membrane, C6, 9L rat glioma, T98G human glioblastoma, or no cells (control) were cocultured. Dexamethasone (0.1 µM), bromophenacyl bromide (1.0 µM), a phospholipase A2 inhibitor, or nothing was added to culture media 72 hours prior to assaying the rat brain capillary endothelium permeability. Permeability was measured as the flux of radiolabeled sucrose across the rat brain capillary endothelium monolayer and then calculated as an effective permeability coefficient (Pe). When neither dexamethasone nor bromophenacyl bromide was present, C6 cells reduced the Pe significantly (p < 0.05), whereas 9L and T98G cells increased Pe significantly (p < 0.05) relative to rat brain capillary endothelium only (control). Dexamethasone reduced Pe significantly for all cell preparations (p < 0.05). The 9L and T98G cell preparations coincubated with dexamethasone had the lowest Pe of all cell preparations. The Pe was not affected in any cell preparation by coincubation with bromophenacyl bromide (p > 0.45). These in vitro BBB experiments showed that: 1) malignant glia, such as 9L and T98G cells, increase Pe whereas C6 cells probably provide an astrocytic influence by reducing Pe; 2) dexamethasone provided significant BBB “tightening” effects both in the presence and absence of glioma cells; 3) the in vivo BBB is actively made more permeable by malignant glia and not simply because of a lack of astrocytic induction; 4) tumor or endothelial phospholipase A2 activity is probably not responsible for glioma-induced increased in BBB permeability; and 5) this model is useful for testing potential agents for BBB protection and for studying the pathophysiology of tumor-induced BBB disruption.

Sign in / Sign up

Export Citation Format

Share Document