Biomedical subjects

Florence Lefranc

Publications and source records attributed to Florence Lefranc.

At least 19 recordsLinked to original sources

PubMed2006

Galectin-1: a small protein with major functions.

Galectins are a family of carbohydrate-binding proteins with an affinity for beta-galactosides. Galectin-1 (Gal-1) is differentially expressed by various normal and pathological tissues and appears to be functionally polyvalent, with a wide range of biological activity. The intracellular and extracellular activity of Gal-1 has been described. Evidence points to Gal-1 and its ligands as one of the master regulators of such immune responses as T-cell homeostasis and survival, T-cell immune disorders, inflammation and allergies as well as host-pathogen interactions. Gal-1 expression or overexpression in tumors and/or the tissue surrounding them must be considered as a sign of the malignant tumor progression that is often related to the long-range dissemination of tumoral cells (metastasis), to their dissemination into the surrounding normal tissue, and to tumor immune-escape. Gal-1 in its oxidized form plays a number of important roles in the regeneration of the central nervous system after injury. The targeted overexpression (or delivery) of Gal-1 should be considered as a method of choice for the treatment of some kinds of inflammation-related diseases, neurodegenerative pathologies and muscular dystrophies. In contrast, the targeted inhibition of Gal-1 expression is what should be developed for therapeutic applications against cancer progression. Gal-1 is thus a promising molecular target for the development of new and original therapeutic tools.

Amino Acid Sequence↗

PubMed2006

Autophagy, the Trojan horse to combat glioblastomas.

Malignant gliomas, among which glioblastomas constitute the largest group, are characterized by a dramatically diffuse infiltration into the brain parenchyma with, as a consequence, the fact that no patient with glioblastoma multiforme (GBM) has been cured to date. Migrating GBM cells are resistant to apoptosis (Type I programmed cell death), and thus to radiotherapy and conventional chemotherapy, because of the constitutive activation of several intracellular signaling pathways, of which the most important identified to date are the pathways controlled by phosphatidylinositol 3-kinase, Akt, and the mammalian target of rapamycin (mTOR). Migrating GBM cells seem to be less prone to resist autophagy (Type II programmed cell death), and disruption of the pathway controlled by mTOR induces marked autophagic processes in GBM cells. Temozolomide is the most efficacious cytotoxic drug employed today to combat glioblastoma, and this drug exerts its cytotoxic activity through proautophagic processes. Thus, autophagy represents a kind of Trojan horse that can be used to bypass, at least partly, the dramatic resistance of glioblastoma to radiotherapy and proapoptotic-related chemotherapy.

Antineoplastic Agents, Phytogenic↗

PubMed2006

A lactosylated steroid contributes in vivo therapeutic benefits in experimental models of mouse lymphoma and human glioblastoma.

Various mono- and disaccharides were grafted onto a steroid backbone. Whereas in vitro these glycosylated steroids had no cytotoxic effects on six different human cancer cell lines, several of the glycosylated steroids under study did significantly modify the levels of in vitro migration of the human U373 glioblastoma, the A549 non-small-cell-lung cancer (NSCLC), and the PC-3 prostate cancer cells, with more pronounced effects in the case of a monosubstituted beta-L-fucopyranosyl-steroid (19), a monosubstituted beta-D-isomaltosyl-steroid (22), and a monosubstituted beta-D-lactosyl-steroid (24). These three compounds significantly increased the survival of conventional mice grafted subcutaneously with the P388 lymphoma, a lymphoma that metastasizes toward the liver. In vivo, the monosubstituted beta-D-lactosyl-steroid (24) also increased the antitumor effectiveness of cisplatin, a cytotoxic pro-apoptotic drug, in the case of the P388 lymphoma model. This compound also increased the survival of immunodeficient mice into whose brains human U373 glioblastoma cells had been orthotopically grafted.

Animals↗

PubMed2006

Endovascular treatment of middle cerebral artery aneurysms.

INTRODUCTION: Until recently, middle cerebral artery (MCA) aneurysms were mostly treated by surgery, and endovascular treatment (EVT) was only performed in selected cases. We prospectively evaluated the feasibility and the results of EVT when it is considered as the first therapeutic option for the treatment of MCA aneurysms. METHODS: From April 2004 to April 2005, 32 patients with 32 MCA aneurysms were treated in our institution. Of these, 12 patients presented with subarachnoid hemorrhage and 20 were asymptomatic. Seven patients were surgically treated because of a compressive haematoma (n = 4), a failure of EVT (n = 1), or because EVT was judged unfeasible (n = 2). In 25 patients, EVT was performed and required the use of the remodelling technique in 16 cases and a stent alone in two. Clinical and anatomical outcome were assessed with the modified Rankin Scale (mRS) at 1 month and a conventional angiography at 6 months. RESULTS: EVT was successfully performed and resulted in an excellent outcome (mRS = 0) in all patients but one, who experienced a thromboembolic complication and maintained a slight lack of vocabulary (mRS = 1). Immediate anatomical results included 15 complete occlusions, 8 neck remnants, and 2 incomplete occlusions in two patients treated by stenting alone. Control angiographies were obtained in 23 patients and showed 17 unchanged occlusions, five slight recanalisations, and one recanalisation that required a retreatment. CONCLUSION: This study showed that EVT of MCA aneurysms is feasible with good results in most patients thanks to new endovascular techniques. However, long-term imaging follow-up is mandatory to confirm these preliminary findings, mostly in terms of anatomical stability.

Adult↗

PubMed2006

Present and potential future issues in glioblastoma treatment.

The treatment of glioblastomas requires a multidisciplinary approach that takes the presently incurable nature of the disease into consideration. Treatments are multimodal and include surgery, radiotherapy and chemotherapy. Current recommendations are that patients with glioblastomas should undergo maximum surgical resection, followed by concurrent radiation and chemotherapy with the novel alkylating drug temozolomide. This is then to be followed by additional adjuvant temozolomide for a period of up to 6 months. Major advances in surgical and imaging technologies used to treat glioblastoma patients are described. These technologies include magnetic resonance imaging and metabolic data that are helpful in the diagnosis and guiding of surgical resection. However, glioblastomas almost invariably recur near their initial sites. Disease progression usually occurs within 6 months and leads rapidly to death. A number of signaling pathways can be activated constitutively in migrating glioma cells, thus rendering these cells resistant to proapoptotic insults, such as conventional chemotherapies. Therefore, the molecular and cellular therapies and local drug delivery that could be used to complement conventional treatments are described, and some of the currently ongoing clinical trials are reviewed, with respect to these new approaches.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2006

Anti-galectin compounds as potential anti-cancer drugs.

Galectins form a family of carbohydrate-binding proteins defined by their affinity for beta-galactosides containing glycoconjugates. The carbohydrate recognition domain (CRD) is responsible for the specificity of galectins for saccharides. This binding may result in modulated cell proliferation, cell death and cell migration, three processes that are intimately involved in cancer initiation and progression. Galectins can also display protein-protein types of interactions with their binding partners. Certain galectins directly involved in cancer progression seem to be promising targets for the development of novel therapeutic strategies to combat cancer. Indeed, migrating cancer cells resistant to apoptosis still constitute the principal target for the cytotoxic drugs used to treat cancer patients. Reducing the levels of migration in apoptosis-resistant cancer cells can restore certain levels of sensitivity to apoptosis (and so to pro-apoptotic drugs) in restricted-migration cancer cells. Anti-galectin agents can restrict the levels of migration of several types of cancer cell and should therefore be used in association with cytotoxic drugs to combat metastatic cancer. We provide experimental proof in support of this concept. While the present review focuses on various experimental strategies to impair cancer progression by targeting certain types of galectins, it pays particular attention to glioblastomas, which constitute the ultimate level of malignancy in primary brain tumors. Glioblastomas form the most common type of malignant brain tumor in children and adults, and no glioblastoma patient has been cured to date.

Antineoplastic Agents↗

PubMed2006

Integrated positron emission tomography and magnetic resonance imaging-guided resection of brain tumors: a report of 103 consecutive procedures.

OBJECT: The aim of this study was to evaluate the integration of positron emission tomography (PET) scanning data into the image-guided resection of brain tumors. METHODS: Positron emission tomography scans obtained using fluorine-18 fluorodeoxyglucose (FDG) and L-[methyl-11C]methionine (MET) were combined with magnetic resonance (MR) images in the navigational planning of 103 resections of brain tumors (63 low-grade gliomas [LGGs] and 40 high-grade gliomas [HGGs]). These procedures were performed in 91 patients (57 males and 34 females) in whom tumor boundaries could not be accurately identified on MR images for navigation-based resection. The level and distribution of PET tracer uptake in the tumor were analyzed to define the lesion contours, which in turn yielded a PET volume. The PET scanning-demonstrated lesion volume was subsequently projected onto MR images and compared with MR imaging data (MR volume) to define a final target volume for navigation-based resection-the tumor contours were displayed in the microscope's eyepiece. Maximal tumor resection was accomplished in each case, with the intention of removing the entire area of abnormal metabolic activity visualized during surgical planning. Early postoperative MR imaging and PET scanning studies were performed to assess the quality of tumor resection. Both pre- and postoperative analyses of MR and PET images revealed whether integrating PET data into the navigational planning contributed to improved tumor volume definition and tumor resection. Metabolic information on tumor heterogeneity or extent was useful in planning the surgery. In 83 (80%) of 103 procedures, PET studies contributed to defining a final target volume different from that obtained with MR imaging alone. Furthermore, FDG-PET scanning, which was performed in a majority of HGG cases, showed that PET volume was less extended than the MR volume in 16 of 21 cases and contributed to targeting the resection to the hypermetabolic (anaplastic) area in 11 (69%) of 16 cases. Performed in 59 LGG cases and 23 HGG cases, MET-PET demonstrated that the PET volume did not match the MR volume and improved the tumor volume definition in 52 (88%) of 59 and 18 (78%) of 23, respectively. Total resection of the area of increased PET tracer uptake was achieved in 54 (52%) of 103 procedures. CONCLUSIONS: Imaging guidance with PET scanning provided independent and complementary information that helped to assess tumor extent and plan tumor resection better than with MR imaging guidance alone. The PET scanning guidance could help increase the amount of tumor removed and target image-guided resection to tumor portions that represent the highest evolving potential.

Adolescent↗

PubMed2006

Cimetidine, an unexpected anti-tumor agent, and its potential for the treatment of glioblastoma (review).

Cimetidine (CIM), the prototypical histamine H2 receptor antagonist (H2RA), was brought to market based on its ability to accelerate healing of gastrointestinal ulcers through the inhibition of gastric acid secretion. Cimetidine, the most studied H2RA, has been demonstrated to possess anti-tumor activity against colon, gastric and kidney cancers, and melanomas. This activity involves a number of different mechanisms of action: a) CIM antagonizes tumor cell-mediated interleukin-1-induced activation of selectins in liver sinusoids, inhibiting tumor cell binding on liver sinusoids, thereby reducing the development of liver metastasis; b) histamine acts as a growth factor in various tumor cell types via the activation of H2 receptors; CIM therefore may antagonize this effect; c) CIM acts as an immunomodulator by enhancing the host's immune response to tumor cells. With respect to malignant gliomas, CIM added to temozolomide was superior in vivo when compared to temozolomide alone in extending survival of nude mice with human glioblastoma cells orthotopically xenografted into their brain. We review the various mechanisms of action potentially associated with the therapeutic effects of CIM in the case of experimental glioblastomas, observations we hope will encourage clinical investigation of CIM in the management of highly malignant gliomas.

Antineoplastic Agents↗

PubMed2005

Galectin-1 knocking down in human U87 glioblastoma cells alters their gene expression pattern.

We have previously reported that (i) progression of malignancy in patients bearing astrocytic tumors correlates with increased tumor levels of galectin-1; (ii) in vitro addition of purified galectin-1 to U87 human glioblastoma cells enhances tumor cell motility; and (iii) conversely, knocking down galectin-1 expression in this cell line by stable transfection with antisense galectin-1 mRNA impairs motility and delays mortality after their intracranial grafting to nude mice. We here used cDNA microarray analysis to compare the effect on gene expression of stable transfection with antisense galectin-1 vector to mock-transfected and wild-type cells. Among the 631 spots probing genes potentially involved in cancer that were valid for analysis on all the arrays the expression of 86 genes was increased at least 2-fold. Confirmation of increased protein levels was provided by immunocytochemistry for p21waf/cip1, cullin-2, p53, ADAM-15, and MAP-2. Major differences in the expression patterns of ADAM-15 and the actin stress fiber organization were also observed. U87 cells stably deficient for galectin-1 expression were significantly less motile than control. We conclude that the stable inhibition of galectin-1 expression alters the expression of a number of genes that either directly or indirectly influence adhesion, motility and invasion of human glioblastoma cells.

Cell Line, Tumor↗

PubMed2005

Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis.

PURPOSE: The present review aims to emphasize that malignant gliomas are characterized by the diffuse invasion of distant brain tissue by a myriad of single migrating cells that exhibit decreased levels of apoptosis (programmed cell death type I), thus a resistance to cytotoxic insult. METHODS: The present review surveys the molecular mechanisms of migration in malignant gliomas and potential issues arising from treatments, in addition to relationships between glioma cell migration and resistance to apoptosis in terms of the molecular signaling pathways. RESULTS: Clinical and experimental data demonstrate that glioma cell migration is a complex combination of multiple molecular processes, including the alteration of tumor cell adhesion to a modified extracellular matrix, the secretion of proteases by the cells, and modifications to the actin cytoskeleton. Intracellular signaling pathways involved in the acquisition of resistance to apoptosis by migrating glioma cells concern PI3K, Akt, mTOR, NF-kappaB, and autophagy (programmed cell death type II). CONCLUSION: A number of signaling pathways can be constitutively activated in migrating glioma cells, thus rendering these cells resistant to cytotoxic insults. However, these pathways are not all constitutively activated at the same time in any one glioma. Particular inhibitors should therefore only be chosen if the target is present in the tumor tissue, but this is only possible if individual patients are submitted to the molecular profiling of their tumors before undergoing any treatment to combat their migratory glioma cells. Specific antimigratory compounds should be added to conventional radio- and/or chemotherapy.

Apoptosis↗

PubMed2005

Monitoring the expression profiles of integrins and adhesion/growth-regulatory galectins in adamantinomatous craniopharyngiomas: their ability to regulate tumor adhesiveness to surrounding tissue and their contribution to prognosis.

OBJECTIVE: The purpose of this study was to identify biological markers that may be involved in the adhesiveness of craniopharyngiomas to optical chiasms and/or pituitary stalks. METHODS: We determined the complete pattern of integrin expression in three craniopharyngiomas by means of a complementary deoxyribonucleic acid microarray. We quantitatively determined the levels of immunohistochemical expression of the different integrins in a series of 37 cases and the pattern of immunohistochemical expression of 10 extracellular matrix components (acting as integrin ligands) in 7 optical chiasms and 11 pituitary stalks. We also quantitatively (computer-assisted microscopy) determined the levels of immunohistochemical expression of galectin-1, -3, -4, -7, and -8 in 50 adamantinomatous craniopharyngiomas. RESULTS: The present study shows that at both the ribonucleic acid and protein levels, adamantinomatous craniopharyngiomas express the alpha2, alpha6, alpha(v), beta1, beta5, and beta8 integrin subunits, whereas optical chiasms and pituitary stalks express vitronectin, thrombospondin, and various forms of collagens. CONCLUSION: Our data suggest that at least part of the adhesiveness of craniopharyngiomas to the surrounding tissue, such as optical chiasms and pituitary stalks, could be explained by the interactions between alpha(2beta1) integrin expressed by craniopharyngiomas and collagens on the one hand, and vitronectin expressed by the surrounding tissue on the other hand. In addition, a Cox regression analysis has revealed that the levels of galectin-4 contribute significant information toward the delay in recurrence independently of surgical status.

Carotid Artery, Internal↗

PubMed2005

Combined cimetidine and temozolomide, compared with temozolomide alone: significant increases in survival in nude mice bearing U373 human glioblastoma multiforme orthotopic xenografts.

OBJECT: Malignant gliomas consist of both heterogeneous proliferating and migrating cell subpopulations, with migrating glioma cells exhibiting less sensitivity to antiproliferative or proapoptotic drugs than proliferative cells. Therefore, the authors combined cimetidine, an antiinflammatory agent already proven to act against migrating epithelial cancer cells, with temozolomide to determine whether the combination induces antitumor activities in experimental orthotopic human gliomas compared with the effects of temozolomide alone. METHODS: Cimetidine added to temozolomide compared with temozolomide alone induced survival benefits in nude mice with U373 human glioblastoma multiforme (GBM) cells orthotopically xenografted in the brain. Computer-assisted phase-contrast microscopy analyses of 9L rat and U373 human GBM cells showed that cimetidine significantly decreased the migration levels of these tumor cells in vitro at concentrations at which tumor growth levels were not modified (as revealed on monotetrazolium colorimetric assay). Computer-assisted microscope analyses of neoglycoconjugate-based glycohistochemical staining profiles of 9L gliosarcomas grown in vivo revealed that cimetidine significantly decreased expression levels of endogenous receptors for fucose and, to a lesser extent, for N-acetyl-lactosamine moieties. Endogenous receptors of this specificity are known to play important roles in adhesion and migration processes of brain tumor cells. CONCLUSIONS: Cimetidine, acting as an antiadhesive and therefore an antimigratory agent for glioma cells, could be added in complement to the cytotoxic temozolomide compound to combat both migrating and proliferating cells in GBM.

Adjuvants, Immunologic↗

PubMed2005

Ventriculostomy-related infections in critically ill patients: a 6-year experience.

OBJECT: The authors undertook a study to analyze the risk factors for ventriculostomy-related infections (VRIs) in critically ill patients and their relation with outcome. METHODS: Demographic, clinical, laboratory, and microbiological data were collected from all 638 consecutive adult patients in whom an external ventriculostomy catheter was placed for monitoring during a 6-year period; patients were treated in a 31-bed intensive care unit (ICU) of a teaching hospital. Of 3726 cerebrospinal fluid (CSF) culture samples analyzed, 1348 (217 patients) showed bacterial growth; of these 97 (obtained in 58 patients [9%]) were considered to represent an infection, 106 (in 68 patients [11%]) colonization, and 145 (in 91 patients [14%]) contamination. Hence, a VRI was diagnosed in 58 (9%) of 638 patients. There were no significant differences in Acute Physiology and Chronic Health Evaluation II score, Glasgow Coma Scale score, and mortality rate, but patients with a VRI stayed longer in the ICU than those without one (p = 0.02). The duration of ventriculostomy monitoring was longer in patients with VRI (median 15 and 9 days, respectively; p = 0.02). Although the daily drained volume of CSF was higher after onset of the infection than before infection in patients with VRI (124 +/- 36 and 85 +/- 14 ml/day, respectively), the need for ventriculoperitoneal shunt placement was no more common in those with VRI than in those without (12 and 15%, respectively; p = 0.2). Multivariate logistic regression revealed that subarachnoid hemorrhage (SAH), intraventricular hemorrhage (IVH), craniotomy, and coinfection were risk factors for VRIs. CONCLUSIONS: In this large series of patients, VRI was associated with a longer ICU stay, but its presence did not influence survival. A longer duration of ventriculostomy catheter monitoring in patients with VRI might be due to an increased volume of drained CSF during infection. Risk factors associated with VRIs are SAH, IVH, craniotomy, and coinfection.

Adolescent↗

PubMed2004

Characterization of gastrin-induced proangiogenic effects in vivo in orthotopic U373 experimental human glioblastomas and in vitro in human umbilical vein endothelial cells.

PURPOSE: This study aims to investigate the role of gastrin-17 (G17) on angiogenesis features in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: The influences of G17 and G17 receptor antagonists were characterized in vitro in terms of angiogenesis on human umbilical vein endothelial cell (HUVEC) tubulogenesis processes on Matrigel and in vivo with respect to U373 orthotopic glioma xenografts. The influence of phosphatidylinositol 3'-kinase, protein kinase C, and nuclear factor-kappaB inhibitors was characterized in vitro on G17-mediated HUVEC tubulogenesis. G17-mediated release of interleukin (IL)-8 from HUVECs and G17-induced modifications in nuclear factor-kappaB DNA binding activity were characterized by means of specific enzyme-linked immunosorbent assays. The influence of G17 on E- and P-selectin expression was determined by means of computer-assisted microscopy, whereas the influence of E- and P-selectin on HUVEC migration was approached by means of antisense oligonucleotides. The chemotactic influence of G17 and IL-8 on HUVEC migration was characterized by means of computer-assisted videomicroscopy with Dunn chambers. RESULTS: Messenger RNAs for cholecystokinin (CCK)A, CCKB, and CCKC receptors were present in HUVECs and microvessels dissected from a human glioblastoma. Whereas G17 significantly increased the levels of angiogenesis in vivo in the U373 experimental glioma model and in vitro in the HUVECs, the CCKB receptor antagonist L365,260 significantly counteracted the G17-mediated proangiogenic effects. G17 chemoattracted HUVECs, whereas IL-8 failed to do so. IL-8 receptor alpha (CXCR1) and IL-8 receptor beta (CXCR2) mRNAs were not detected in these endothelial cells. Gastrin significantly (but only transiently) decreased the level of expression of E-selectin, but not P-selectin, whereas IL-8 increased the expression of E-selectin. Specific antisense oligonucleotides against E- and P-selectin significantly decreased HUVEC tubulogenesis processes in vitro on Matrigel. CONCLUSIONS: The present study shows that gastrin has marked proangiogenic effects in vivo on experimental gliomas and in vitro on HUVECs. This effect depends in part on the level of E-selectin activation, but not on IL-8 expression/release by HUVECs.

Animals↗

PubMed2004

Magnetic resonance angiography image guidance for the microsurgical clipping of intracranial aneurysms: a report of two cases.

To describe the integration of magnetic resonance angiography (MRA) in neuronavigation procedures for microsurgery of intracranial aneurysms. MRA was combined with standard magnetic resonance image (MRI) acquisition in the image-guided planning for the microsurgical clipping of a saccular aneurysm in two patients (one 3-mm large middle cerebral artery and one 8-mm large pericallosal artery aneurysm, diagnosed by catheter angiography in both patients) using two different neurosurgical navigation systems. Conventional 3-D T1-weighted MRI with gadolinium and MRA pulse sequences were acquired in frameless stereotactic conditions the day before surgery and thereafter registered, allowing the definition a minimally invasive straight trajectory to the aneurysm neck. MRA-guided neurosurgery allowed a direct approach to the aneurysms at their proper location, reducing the invasiveness of the approach by tailoring the bone opening and reducing the duration and extension of brain retraction. The technique also avoided unnecessary dissection and exposure of the main trunks and collateral vessels. The aneurysms were successfully eradicated without complication. Integration of MRA in the planning and neuronavigation procedure for intracranial aneurysms may minimize the morbidity related to the surgical approach. This technique may be applicable more routinely using standard neuronavigation equipment.

Adult↗

PubMed2003

Characterization of gastrin-induced cytostatic effect on cell proliferation in experimental malignant gliomas.

OBJECTIVE: Growth patterns of astrocytic tumors can be modulated in vitro by gastrin. In this study, the influence of gastrin on the in vitro cell cycle kinetics and the in vivo growth features of three experimental malignant gliomas was investigated. METHODS: Gastrin-induced influence on overall growth was assayed in vitro by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium colorimetric assay for human U373 and rat C6 gliomas and for rat 9L gliosarcoma. Although cell cycle analyses were performed by means of computer-assisted microscope analyses of Feulgen-stained nuclei, the gastrin-induced effects of the levels of expression of cyclins D3 and E, CDK2, CDK4, CDK5, CDK7, p15, p16, E2F1, and E2F2 were assayed by means of quantitative Western blot test. The presence of ribonucleic acids for the CCK(B) and CCK(C) gastrin receptors in the U373, C6, and 9L models was assayed by means of quantitative reverse transcriptase-polymerase chain reaction, and the presence or absence of ribonucleic acids for CCK(A) receptor was checked by means of conventional polymerase chain reaction. The influence of gastrin was also characterized in vivo in terms of the survival periods of conventional rats orthotopically grafted with the C6 and 9L models and nude rats with the U373 model. RESULTS: Gastrin significantly decreased the overall growth rate in the rat C6 and the human U373 high-grade astrocytic tumor models with either CCK(B) or CCK(C) gastrin receptor but not in the 9L rat gliosarcoma, which had no CCK(B) gastrin receptor (but had CCK(A) receptor) and only weak amounts of CCK(C) receptor. This effect seems to occur via a cytostatic effect; that is, an accumulation of tumor astrocytes occurs in the G(1) cell cycle phase. The cytostatic effect could relate to a gastrin-induced decrease in the amounts of the cyclin D3-CDK4 complex in both C6 and U373 glioma cells. In vivo, gastrin significantly increased the survival periods of C6 and U373 glioma-bearing rats, but not of 9L gliosarcoma-bearing rats. CONCLUSION: Gastrin is able to significantly modify the growth levels of a number of experimental gliomas.

Animals↗

PubMed2003

Characterization of the levels of expression of retinoic acid receptors, galectin-3, macrophage migration inhibiting factor, and p53 in 51 adamantinomatous craniopharyngiomas.

OBJECT: Craniopharyngiomas are histopathologically defined as benign tumors that can behave very aggressively at the clinical level. They can originate from different types of embryonal epithelial tissue in which correct spatiotemporal regulation has been disrupted at the effector production level. The goal of this study was to determine the efficacy of using selected biological markers to distinguish between recurring and nonrecurring craniopharyngiomas. METHODS: The authors used computer-assisted microscopy to determine quantitatively the immunohistochemical levels of expression of selected markers, including retinoic acid receptors (RARs), as response elements to retinoic acid in a series of 51 adamantinomatous craniopharyngiomas. These tumors may also originate as the result of physiological defects in the apoptosis-mediated elimination of embryological remnants of epithelial tissue. Galectin-3, p53, and the macrophage migration inhibiting factor (MIF) are known to play crucial roles in these processes. The authors quantitatively determined the levels of expression of these substances in this series of 51 craniopharyngiomas. The data show that all craniopharyngiomas were immunoreactive for RARalpha, whereas their immunoreactivity for RARbeta and RARgamma varied dramatically from one case to another. Craniopharyngiomas with low levels of RARbeta and high levels of RARgamma are more likely to recur than those with higher levels of RARbeta and lower levels of RARgamma. Rapidly recurring craniopharyngiomas also show significantly lower levels of expression of galectin-3 and MIF than nonrecurring or slowly recurring cases. Few tumors exhibited p53 immunopositivity. CONCLUSIONS: The data indicate that even in the so-called adamantinomatous group of craniopharyngiomas, several subgroups with different clinical behavior patterns can be identified on the basis of differentiation markers relating mainly to the presence or absence of RARbeta and RARgamma.

Adolescent↗

PubMed2003

Determination of RNA expression for cholecystokinin/gastrin receptors (CCKA, CCKB and CCKC) in human tumors of the central and peripheral nervous system.

Gastrin (G17) belongs to the cholecystokinin (CCK) peptide family widely distributed in the brain, and we were the first to show that it significantly modulates the growth and migration features of tumor astyrocytes. Conflictual data have been published as to whether CCKA, CCKB and CCKC receptors are, or are not, present in tumors of the central and peripheral nervous system (CPNS) in general, and in gliomas in particular. In the present study we employed polymerase chain reaction (PCR) on a series of 29 CNPS tumors, including 20 gliomas (17 astrocytic and 3 oligodendroglial tumors), 4 schwannomas and 5 meningiomas to investigate whether RNAs were present or absent in the case of these CCKA, CCKB and CCKC receptors. The presence of the three CCK receptor subtypes was also assayed on three experimental models, i.e. the U373 human glioma, the C6 rat glioma and the 9L rat gliosarcoma. The data show that 9/20 (45%) of the gliomas exhibited RNAs for the CCKB receptor as did the C6 rat glioma, 13/20 (65%) RNAs for the CCKC receptor as did the U373 human glioma and the 9L rat gliosarcoma. Of the 20 gliomas, 17 (85%) expressed RNAs for either the CCKB or the CCKC receptor (or both), a feature which was also observed in the experimental models. One schwannoma and one meningioma exhibited RNAs for the CCKB receptor, while 4/4 schwannomas and 4/5 meningiomas showed RNAs for the CCKC receptor. None of the gliomas, schwannomas or meningiomas exhibited RNAs for the CCKA receptor, which were found in the 9L rat gliosarcoma model only. These data emphasize that 85% of the gliomas under study and 86% (25/29) of the tumors of the central and peripheral nervous system exhibited CCKB and/or CCKC receptors. This therefore suggests an important role for gastrin in the biological development of these tumors.

Animals↗