Biomedical subjects

G Y Gillespie

Publications and source records attributed to G Y Gillespie.

At least 37 records · Page 2Linked to original sources

PubMed1999

Glioma migration can be blocked by nontoxic inhibitors of myosin II.

Anaplastic gliomas are infiltrative tumors, and their ability to migrate through normal brain contributes to their highly malignant behavior. Invasion of brain requires cell motility, which in turn depends on the activity of the cytoskeleton. A cytoskeletal component central to this process is myosin II, the cytoplasmic analogue of smooth and skeletal muscle myosin. Myosin II activity is regulated by the enzyme myosin light chain kinase, which activates myosin II by phosphorylating it on its regulatory light chain. We have investigated the role of myosin II in glioma motility and invasiveness by examining the effects of two inhibitors of myosin light chain kinase, ML7 and KT5926. Both drugs are potent inhibitors of both glioma motility, as measured by a scrape motility assay, and an in vitro haptotaxis assay. The inhibition of in vitro haptotaxis follows the dose-response relationship expected for competitive inhibition of myosin light chain kinase by these drugs and is seen at drug concentrations that are nontoxic. These results highlight the important role that myosin II contributes to glioma invasiveness and suggest that it may serve as a target in future strategies at blocking invasion by these tumors.

Actin Cytoskeleton↗

PubMed1999

Malignant human gliomas express an amiloride-sensitive Na+ conductance.

Human astrocytoma cells were studied using whole cell patch-clamp recording. An inward, amiloride-sensitive Na+ current was identified in four continuous cell lines originally derived from human glioblastoma cells (CH235, CRT, SKMG-1, and U251-MG) and in three primary cultures of cells obtained from glioblastoma multiforme tumors (up to 4 passages). In addition, cells freshly isolated from a resected medulloblastoma tumor displayed this same characteristic inward current. In contrast, amiloride-sensitive currents were not observed in normal human astrocytes, low-grade astrocytomas, or juvenile pilocytic astrocytomas. The only amiloride-sensitive Na+ channels thus far molecularly identified in brain are the brain Na+ channels (BNaCs). RT-PCR analyses demonstrated the presence of mRNA for either BNaC1 or BNaC2 in these tumors and in normal astrocytes. These results indicate that the functional expression of amiloride-sensitive Na+ currents is a characteristic feature of malignant brain tumor cells and that this pathway may be a potentially useful target for therapeutic intervention.

Amiloride↗

PubMed1999

Receptor for interleukin 13 is abundantly and specifically over-expressed in patients with glioblastoma multiforme.

We have recently documented that the vast majority of patients with glioblastoma multiforme (GBM) over-express a receptor (R) for interleukin 13 (IL13) in situ. We have now evaluated further the degree of relative specificity of the binding of IL13 to GBM when compared with other growth factor receptors. Tumor samples of 11 patients with GBM, 7 various normal brain samples, and several cell lines in culture were examined. Same patient tissue sections were incubated with 125I-labeled: IL13, monoclonal antibody HB21 against human transferrin (Tf) receptor, epidermal growth factor (EGF), and an IL4 antagonist, IL4.Y124D. All 11 GBMs stained specifically, densely, and relatively homogeneously for both IL13R and TfR. Seven GBM specimens showed specific binding for 125I-EGF, but it was less homogeneous when compared with IL13R or TfR. Two of the GBMs studied demonstrated extremely high density of the EGFR. Furthermore, we did not detect significant presence of the IL4R in the studied GBM specimens in situ. All sections of non-malignant brain tissues examined showed avid binding by the TfR with lack of consistent and specific binding of 125I-IL13 or -EGF. Thus, it appears that the GBM-associated IL13R is considerably more specific to GBM that the one for Tf and more frequently and homogeneously expressed than the EGFR. These results render further support for the hIL13R being a new unique candidate for delivery of variety of anti-GBM therapies.

Autoradiography↗

PubMed1999

Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas.

Glioblastoma multiforme (GBM) is an incurable brain tumor. Due to the striking heterogeneity that characterizes GBM, there is no known tumor-specific antigen or receptor that is expressed by a majority of GBM patients. We found that virtually all studied human GBM specimens (23 samples) abundantly expressed a receptor for interleukin (IL)-13 in situ, whereas normal human brain had few, if any, IL-13-binding sites. The GBM-associated IL-13 receptor was both quantitatively and qualitatively different from and, thus, more restrictive than the shared signaling receptor of normal tissue: it was IL-4 independent. The receptor for IL-13 was overexpressed by a majority of cancer cells in situ. Furthermore, cytotoxins targeted to this more restrictive IL-13R produced cures in animals bearing xenografts of human high-grade gliomas. Thus, unexpectedly, the receptor for an immune regulatory cytokine may be a long sought marker and, concomitantly, a unique imaging site and therapeutic target for GBM, the most malignant and the most heterogeneous of brain tumors.

Adolescent↗

PubMed1999

Ionizing radiation improves survival in mice bearing intracranial high-grade gliomas injected with genetically modified herpes simplex virus.

Malignant gliomas remain incurable with current interventions. Encouraging investigational approaches include the use of genetically modified herpes simplex-1 (HSV-1) viruses as direct cytotoxic agents. Combining attenuated HSV-1 with standard therapy, human U-87 malignant glioma xenografts grown in the hind limb or intracranially in athymic nude mice were exposed to ionizing radiation, inoculated with genetically modified HSV R3616, or received both virus and radiation. The combination of virus with fractionated ionizing radiation suggests a synergistic action and results in reduced tumor volumes and longer survivals when compared with treatment with either modality alone.

Animals↗

PubMed1998

Differential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer.

Adenovirus (Ad) vectors are promising for gene therapy of glioma due to their ability to achieve efficient gene transfer upon intratumoral administration. Yet in this context, Ad mediates widespread gene transfer to both tumor and surrounding parenchyma. Ad entry is dependent upon the expression of fiber receptors, such as coxsackie/adenovirus receptor, and alpha(v) integrins on the target cells for binding and internalization, respectively. We hypothesized that the susceptibility of human gliomas to Ad would likely be heterogeneous due to variable expression of these receptors. It was found that established human glioma cell lines exhibited differential susceptibility to Ad-mediated gene transfer, which correlated directly with the level of radiolabeled Ad binding and with the expression of coxsackie/adenovirus receptor but not with the expression of alpha(v) integrins. To circumvent the lack of fiber receptors and to target Ad gene transfer specifically to tumor cells, we used a bispecific antibody conjugate to ablate Ad binding to fiber receptors and retarget binding to the epidermal growth factor receptor (EGFR), a tumor-associated marker negligibly expressed in normal, mitotically quiescent neural tissues. The results demonstrate that EGFR-targeted Ad gene transfer was EGFR specific and independent of fiber-fiber receptor interactions. Furthermore, EGFR targeting significantly enhanced Ad gene delivery to 7 of 12 established glioma cell lines and to 6 of 8 cultured primary gliomas. Interestingly, EGFR-targeted Ad gene transfer did not correlate with EGFR expression across cell lines, suggesting the importance of other factors. This study establishes that fiber receptor expression limits the utility of Ad vectors for gene transfer to glioma cells and suggests that targeting Ad via EGFR may prove valuable for tumor-specific gene transfer to high-grade gliomas. These findings have key relevance in the context of Ad vector-based approaches for glioma gene therapy.

Adenoviruses, Human↗

PubMed1998

Paracrine expression of a native soluble vascular endothelial growth factor receptor inhibits tumor growth, metastasis, and mortality rate.

Vascular endothelial growth factor (VEGF) is a potent and selective vascular endothelial cell mitogen and angiogenic factor. VEGF expression is elevated in a wide variety of solid tumors and is thought to support their growth by enhancing tumor neovascularization. To block VEGF-dependent angiogenesis, tumor cells were transfected with cDNA encoding the native soluble FLT-1 (sFLT-1) truncated VEGF receptor which can function both by sequestering VEGF and, in a dominant negative fashion, by forming inactive heterodimers with membrane-spanning VEGF receptors. Transient transfection of HT-1080 human fibrosarcoma cells with a gene encoding sFLT-1 significantly inhibited their implantation and growth in the lungs of nude mice following i.v. injection and their growth as nodules from cells injected s.c. High sFLT-1 expressing stably transfected HT-1080 clones grew even slower as s.c. tumors. Finally, survival was significantly prolonged in mice injected intracranially with human glioblastoma cells stably transfected with the sflt-1 gene. The ability of sFLT-1 protein to inhibit tumor growth is presumably attributable to its paracrine inhibition of tumor angiogenesis in vivo, since it did not affect tumor cell mitogenesis in vitro. These results not only support VEGF receptors as antiangiogenic targets but also demonstrate that sflt-1 gene therapy might be a feasible approach for inhibiting tumor angiogenesis and growth.

Animals↗

PubMed1998

Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human cells.

Activation of purine nucleoside analogs by Escherichia coli purine nucleoside phosphorylase (PNP) is being evaluated as a suicide gene therapy strategy for the treatment of cancer. Because the mechanisms of action of two toxic purine bases, 6-methylpurine (MeP) and 2-fluoroadenine (F-Ade), that are generated by this approach are poorly understood, mechanistic studies were initiated to learn how these compounds differ from agents that are being used currently. The concentration of F-Ade, MeP, or 5-fluorouracil required to inhibit CEM cell growth by 50% after a 4-hr incubation was 0.15, 9, or 120 microM, respectively. F-Ade and MeP were also toxic to quiescent MRC-5, CEM, and Balb 3T3 cells. Treatment of CEM, MRC-5, or Balb 3T3 cells with either F-Ade or MeP resulted in the inhibition of protein, RNA, and DNA syntheses. CEM cells converted F-Ade and MeP to F-ATP and MeP-ribonucleoside triphosphate (MeP-R-TP), respectively. The half-life for disappearance of HeP-ribonucleoside triphosphate from CEM cells was approximately 48 hr, whereas the half-lives of F-ATP and ATP were approximately 5 hr. Both MeP and F-Ade were incorporated into the RNA and DNA of CEM cells. These studies indicated that the mechanisms of action of F-Ade and MeP were quite different from those of other anticancer agents, and suggested that the generation of these agents in tumor cells by E. coli PNP could result in significant advantages over those generated by either herpes simplex virus thymidine kinase or E. coli cytosine deaminase. These advantages include a novel mechanism of action resulting in toxicity to nonproliferating and proliferating tumor cells and the high potency of these agents during short-term treatment.

3T3 Cells↗

PubMed1998

Intracellular expression of a single-chain antibody directed against human papillomavirus type 16 E7 oncoprotein achieves targeted antineoplastic effects.

Human papillomavirus type 16 (HPV16) E7 is a viral oncoprotein that is believed to play a major role in cervical neoplasia. Anti-HPV16 E7 intracellular single-chain antibodies (scFvs) were constructed to down-regulate HPV16 E7 oncoprotein in HPV DNA-containing cell lines. In these studies, we transfected anti-E7 scFvs into the HPV16-positive human cervical carcinoma cell lines CaSki and SiHa and tested them for their ability to inhibit cell proliferation and alter the level of HPV16 E7 oncoprotein. Our results showed that anti-HPV16 E7 scFvs inhibited cell proliferation by >85% in CaSki cells and by 95% in SiHa cells. E7 oncoprotein was down-regulated by anti-HPV16 E7 scFv, and its expression was inversely related to the amount of scFv transfected. However, there were no effects of transfecting scFvs alone in HPV-negative cell lines. These results imply that anti-HPV16 E7 scFvs only have specific anti-HPV16 E7 effects on cell proliferation and on the synthesis of virally encoded proteins in HPV-positive cell lines. Thus, transfection of HPV16 E7-positive tumors with antigen-specific scFvs may be a viable strategy for cervical cancer gene therapy.

Animals↗

PubMed1998

Expression of voltage-activated chloride currents in acute slices of human gliomas.

Using whole-cell patch-clamp recordings, we identified a novel voltage-activated chloride current that was selectively expressed in glioma cells from 23 patient biopsies. Chloride currents were identified in 64% of glioma cells studied in acute slices of nine patient biopsies. These derived from gliomas of various pathological grades. In addition, 98% of cells acutely isolated or in short-term culture from 23 patients diagnosed with gliomas showed chloride current expression. These currents, which we termed glioma chloride currents activated at potentials >45 mV, showed pronounced outward rectification, and were sensitive to bath application of the presumed Cl- channel specific peptide chlorotoxin (approximately 600 nM) derived from Leiurus scorpion venom. Interestingly, low grade tumours (e.g., pilocytic astrocytomas), containing more differentiated, astrocyte-like cells showed expression of glioma chloride currents in concert with voltage-activated sodium and potassium currents also seen in normal astrocytes. By contrast, high grade tumours (e.g., glioblastoma multiforme) expressed almost exclusively chloride currents, suggesting a gradual loss of Na+ currents and gain of Cl- currents with increasing pathological tumour grade. To expand on the observation that these chloride currents are glioma-specific, we introduced experimental tumours in scid mice by intracranial injection of D54MG glioma cells and subsequently recorded from tumour cells and adjacent normal glial cells in acute slices. We consistently observed expression of chlorotoxin-sensitive chloride channels in implanted glioma cells, but without evidence for expression of chloride channels in surrounding "normal" host glial cells, suggesting that these chloride channels are probably a glioma-specific feature. Finding of this novel glioma specific Cl- channel in gliomas in situ and it's selective binding of chlorotoxin may provide a way to identify or target glioma cells in the future.

Adolescent↗

PubMed1998

Treatment of intracranial gliomas in immunocompetent mice using herpes simplex viruses that express murine interleukins.

This report describes a test of the hypothesis that the oncolytic effect of genetically engineered, replication competent herpes simplex viruses (HSV) depends both on cell destruction by the virus and an immune response to the tumor cells induced in an immunocompetent animal system. The oncolytic vector was a HSV recombinant virus in which both copies of the gamma 1 34.5 gene were replaced with the murine genes encoding the cytokine interleukin-4 (IL-4) or interleukin-10 (IL-10). The hypothesis predicted that if an immune response plays a role in survival following intratumoral treatment of tumor-bearing animals with HSV, expression of IL-4 should prolong survival whereas expression of IL-10 should reduce it. The results are that (1) these cytokines can be expressed by HSV in productively infected cells both in vitro and in vivo; (2) HSV-expressing IL-4 or IL-10 genes were able to infect and destroy glioma cells in vitro; (3) intracerebral inoculation of HSV expressing either IL-4 or IL-10 into syngeneic murine glioma GL-261 cells implanted in the brains of immunocompetent C57BL/6 mice produced dramatically opposite physiologic responses. The IL-4 HSV significantly prolonged survival of tumor bearers, whereas tumor-bearing mice that received the IL-10 HSV had a median survival that was identical to that of saline treated controls; (4) immunohistochemical analyses of mouse brains at 3 and 7 days after virus inoculation showed marked accumulation of inflammatory cells composed primarily of macrophages/microglia, with various proportions of CD8+ and CD4+ T cells, but few B lymphocytes. We conclude that the cytokines expressed from genes encoded in the viral genome influence HSV therapy of tumors and this is probably due to the host immune response. Thus, cytokine expression may be an important adjunct to tumor therapy utilizing genetically engineered HSV.

Animals↗

PubMed1997

In vivo gene therapy of cancer with E. coli purine nucleoside phosphorylase.

We have developed a new strategy for the gene therapy of cancer based on the activation of purine nucleoside analogs by transduced E. coli purine nucleoside phosphorylase (PNP, E.C. 2.4.2.1). The approach is designed to generate antimetabolites intracellularly that would be too toxic for systemic administration. To determine whether this strategy could be used to kill tumor cells without host toxicity, nude mice bearing human malignant D54MG glioma tumors expressing E. coli PNP (D54-PNP) were treated with either 6-methylpurine-2'-deoxyriboside (MeP-dR) or arabinofuranosyl-2-fluoroadenine monophosphate (F-araAMP, fludarabine, a precursor of F-araA). Both prodrugs exhibited significant antitumor activity against established D54-PNP tumors at doses that produced no discernible systemic toxicity. Significantly, MeP-dR was curative against this slow growing solid tumor after only 3 doses. The antitumor effects showed a dose dependence on both the amount of prodrug given and the level of E. coli PNP expression within tumor xenografts. These results indicated that a strategy using E. coli PNP to create highly toxic, membrane permeant compounds that kill both replicating and nonreplicating cells is feasible in vivo, further supporting development of this cancer gene therapy approach.

Animals↗

PubMed1997

Evaluation of genetically engineered herpes simplex viruses as oncolytic agents for human malignant brain tumors.

Earlier studies have shown that genetically engineered herpes simplex viruses (e.g., HSV-1) are effective in killing malignant tumor cells both in vitro and in various murine tumor models. This report focuses on a panel of five genetically engineered viral mutants of the gamma(1)34.5 gene, which was shown previously to cause reduction in viral replication and associated neurovirulence of HSV. These include R3616, which has both copies of gamma(1)34.5 deleted, R4009, which has a stop codon inserted after codon 28 in both copies of the gamma(1)34.5 gene, R849, which contains a lacZ gene inserted in place of the gamma(1)34.5, R908, which lacks 41 codons in frame after codon 72 of the gamma(1)34.5, and R939, which carries a stop codon precluding the translation of the COOH-terminal domain of the gamma(1)34.5 gene. We report the following: (a) all five mutant HSVs were avirulent in experimental animals but were cytotoxic for human tumor cells in vitro and in vivo; (b) the gamma(1)34.5- HSV replicated in human glioma cells almost as efficiently as wild-type HSV-1(F) based on replication assays, in situ hybridization for viral DNA, and expression of infected cell protein 27; (c) capacity of mutant HSVs to kill human cells derived from glioblastoma multiforme (CH-235MG, D-37MG, D-54MG, D-65MG, U-251MG, U-373MG, and SK-MG-1), anaplastic astrocytoma (Hs-683), anaplastic glioma (U-87MG and U-138MG), gliosarcoma (D-32GS), or normal human astrocytes demonstrated that glioma cells varied in their susceptibility to HSV-mediated cytotoxicity and that cultured astrocytes were two to three orders of magnitude less susceptible to killing than were malignant glia; and (d) scid mice, which received 0.5 or 5 x 10(6) plaque-forming units of R4009, either were coinoculated at the time of intracranial transplantation with 106 U251MG or D-54MG human glioma cells or received the cells intratumorally 5 days after tumor induction and experienced significant increases in median survivals, with no histopathological indication of an infectious encephalitic process. Genetically engineered gamma(1)34.5- HSV mutants appear to be a potentially safe biotherapeutic agent for experimental treatment of uniformly fatal malignant brain tumors.

Acyclovir↗

PubMed1997

Immunoreactivity of human MAb BT32/A6 with neuroepithelial tumors.

The present study was undertaken to determine the pattern of immunoreactivity of BT32/A6, a human IgM monoclonal antibody (MAb), with the following histological panels: 1) 30 human and non-human cell lines, 2) 32 normal human tissues, and 3) 28 tumors of central neuroepithelial origin (16 astrocytic; 11 non-astrocytic). Antibody BT32/A6 recognizes a surface and cytoplasmic antigen present on a variety of human tumor cell lines including gliomas, melanomas, neuroblastomas, and a few sarcomas. The antigen is present (at least focally) on 15/16 astrocytic tumor tissue sections (94%), and in some cases, on close to 100% of cells. All malignant cell types, including small anaplastic cells, giant cells, gemistocytic cells, and cells forming pseudopalisades were labeled by MAb BT32/A6. Non-astrocytic neuroepithelial tumors did not stain appreciably with MAb BT32/A6. There was weak immunoreactivity in a small subset of normal human tissues of epithelial and lymphoid origin, with the exception of adrenal cortex, which exhibited weak to moderate staining. All normal tissues of neuroectodermal and mesenchymal origin were unreactive. In conclusion, MAb BT32/A6 appears to be unique in that it recognizes a highly-expressed astrocytic tumor-associated antigen that is present on both low and high grade tumors. This makes it a strong candidate for further studies aimed at establishing its usefulness in the treatment of human astrocytic tumors.

Antibodies, Monoclonal↗

PubMed1997

In vitro and in vivo gene delivery mediated by a synthetic polycationic amino polymer.

A synthetic polyamino polymer with a glucose backbone was used for gene transfer in vitro and in vivo. Gene transfer in vitro to various human carcinoma cell lines was achieved with an efficiency superior to a commercially available cationic liposome preparation. The polymer was resistant to inhibition by serum, which allowed for efficient gene transfer in vivo. Direct Intracranial tumor injection using this reagent resulted in reporter gene expression levels comparable to those achieved by a recombinant adenoviral vector. Thus, this compound represents a new class of agent that may have broad utility for gene transfer and gene therapy applications.

Animals↗

PubMed1997

Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression.

OBJECTIVE: Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of endothelial cells and increases vascular permeability dramatically. All gliomas secrete significant amounts of VEGF, whereas meningiomas are variable in expression. Thus, we sought to determine whether the extent of VPF/VEGF expression in meningiomas correlated with differences in brain edema associated with these tumors. METHODS: Meningioma tissue samples from 37 patients (15 men, average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent surgery at or were referred to the University of Alabama Hospital were examined retrospectively for the extent of expression of immunoreactive VPF/VEGF. Additionally, peritumoral edema was assessed on a blinded basis radiographically from preoperative magnetic resonance imaging scans. Selected specimens were examined by in situ hybridization to document the source of VPF/VEGF. RESULTS: The predominant meningioma subclassifications were transitional (57%) or meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5, with a median value of 2 on a subjective 5-point scale; magnetic resonance imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale), with a median value of 2.5. The correlation of determination (R2) of magnetic resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal parenchymal brain cells. CONCLUSION: These data suggest that meningioma-associated edema may be a result of the capacity of meningioma cells to produce VPF/VEGF locally, leading to increased tumor neovascularization and enhanced vascular permeability.

Adult↗

PubMed1996

The application of genetically engineered herpes simplex viruses to the treatment of experimental brain tumors.

Due to lack of effective therapy, primary brain tumors are the focus of intense investigation of novel experimental approaches that use vectors and recombinant viruses. Therapeutic approaches have been both indirect, whereby vectors are used, or direct to allow for direct cell killing by the introduced virus. Genetically engineered herpes simplex viruses are currently being evaluated as an experimental approach to eradicate malignant human gliomas. Initial studies with gamma (1)34.5 mutants, R3616 (from which both copies of the gamma (1)34.5 gene have been deleted) and R4009 (a construct with two stop codons inserted into the gamma (1)34.5 gene), have been assessed. In a syngeneic scid mouse intracranial tumor model, recombinant herpes simplex virus can be experimentally used for the treatment of brain tumors. These viruses and additional engineered viruses were subsequently tested in human glioma cells both in vitro and in vivo. Using a xenogeneic scid mouse intracranial glioma model, R4009 therapy of established tumors significantly prolonged survival. Most importantly, long-term survival was achieved, with histologic evidence that R4009 eradicated intracranial tumors in this model. Furthermore, the opportunity to evaluate gamma (1)34.5 mutants that have enhanced oncolytic activity, e.g., R8309 where the carboxyl terminus of the gamma (1)34.5 gene has been replaced by the murine homologue, MyD116, are considered.

Adenoviridae↗

PubMed1996

Human astrocytoma cells express a unique chloride current.

Human astrocytoma cells were studied using whole-cell patch-clamp recording. Voltage-dependent outwardly-rectifying anion currents were identified in primary cultures of six freshly resected human brain tumors and in seven established anaplastic astrocytoma/glioblastoma cell lines (U251MG, CH235MG, U373MG, U105MG, D54MG, SK-MG-1, and STTG1). Anion currents were not observed in normal, non-neoplastic glial cells, nor in human tumor-derived cells of non-glial origin (melanoma, breast cancer, neuroblastoma, rhabdomyosarcoma). Currents activated at potentials > 50 mV and showed large transients upon termination of voltage steps. Currents reversed at the predicted equilibrium potential for chloride ions and could also be recorded when Cl- was replaced by F-, Br- or I-. Currents were inhibited by the Cl- channel blockers chlorotoxin, DIDS, and DNDS. These Cl- currents may play a role in the growth control of astrocytoma cells.

Astrocytoma↗