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Marc Sanson

Publications and source records attributed to Marc Sanson.

35 records · Page 2Linked to original sources
PubMed2004

[Current classification of gliomas].

The histologic classification of gliomas, which is based on oligodendroglial- or astrocytic-like morphology distinguishes gliomas in astrocytic tumors (grade 1- pilocytic astrocytoma to grade 4- glioblastoma), oligodendroglial and mixed tumors (grade 2 and 3) according to cell differenciation, cellularity, nuclear atypia, mitotic activity, necrosis and microvascular proliferation. Prognosis is correlated to grade. Based on interobserver variability, the histological diagnosis is often highly subjective and should be interpreted within the context of clinical and radiological data. Newly identified good prognostic markers (1p and 19q loss in oligodendrogliomas) and new molecular techniques such as microarray may further refine the existing classification.

Brain Neoplasms↗
PubMed2004

[Therapeutic strategies and prospects of gliomas].

The prognosis and the treatment of gliomas depend on age, performance status and histological grade. Symptomatic treatment relies on steroids against cerebral edema, anti-epileptic drugs for seizures and perioperatively, prevention of thrombo-embolism and digestive complications, physiotherapy. Specific therapies include surgery, radiotherapy and chemotherapy. Surgery is necessary for histological diagnosis. In low grade gliomas, it has a significant impact in terms of survival. In malignant gliomas, surgery provides symptomic relief without clearly improving survival. Radiation therapy has been shown to improve survival in malignant glioma, but not in asymptomatic low grade tumors. Chemotherapy has a modest efficacy in glioblastomas, whereas oligodendrogliomas with 1p 19q deletion are chemosensitive tumors.

Age Factors↗
PubMed2004

Distinct responses of xenografted gliomas to different alkylating agents are related to histology and genetic alterations.

A series of 12 human gliomas was established as xenografts in nude mice and used to evaluate the relationship between histology, genetic parameters, and response to alkylating agents. Eight were high-grade oligodendroglial tumors, and four were glioblastoma. They were characterized for their genetic alterations, including those considered as "early" alterations, namely loss of chromosome 1 +/- loss of chromosome 19q, TP53 mutation, and those considered as "late" alterations, namely loss of chromosome 10, loss of chromosome 9p, EGFR genomic amplification, PTEN mutation, CDKN2A homozygous deletion, and telomerase reactivation. Chemosensitivity of xenografts to four alkylating agents, temozolomide (42 mg/kg, days 1-5, p.o.), 1,3-bis(2-chloroethyl)-1-nitrosourea (5 mg/kg, day 1, i.p.), Ifosfamide (90 mg/kg, days 1-3, i.p.), and carboplatin (66 mg/kg, day 1, i.p.) was tested by administration of drugs to tumor-bearing mice. Although each tumor presented an individual response pattern, glioblastoma had a lower chemosensitivity than oligodendrogliomas, and temozolomide was the most effective drug. Deletion of 1p +/- 19q was associated with higher chemosensitivity, whereas late molecular alterations, particularly EGFR amplification, were associated with chemoresistance. These results suggest that the combined use of histology and molecular markers should eventually be helpful selecting the most appropriate agents for treatment of malignant oligodendrogliomas and astrocytomas.

Animals↗
PubMed2004

Analysis of the bHLH transcription factors Olig1 and Olig2 in brain tumors.

In the absence of specific markers, the histological diagnosis of oligodendroglial tumors is based on subjective qualitative criteria and remains controversial. Recently, two bHLH transcription factors involved in oligodendroglial specification, Olig1 and Olig2 have been proposed as potential markers of oligodendrogliomas. Expression of Olig1/2 was analyzed by in situ hybridization on 78 samples including 47 glial, 29 non-glial tumors, and two non-tumoral brain tissues. Both genes had a similar pattern of expression. Olig1 and Olig2 were expressed in 26/30 (87%) and 28/30 (93%) of oligodendroglial tumors respectively but in only 9% of glioblastomas (1/11). Olig genes were also expressed in the low-grade fibrillary astrocytomas (4/4) and anaplastic astrocytomas (2/2). No expression was found in non-glial tumors, except for one primary cerebral lymphoma. Double staining with PLP, NFH, GFAP showed that olig genes were expressed by mature, non-tumoral oligodendrocytes, but not by normal astrocytes or neurones. This study indicates that Olig1/2 expression clearly distinguishes pure Olig-negative glioblastomas from a wide spectrum of Olig-positive tumors including traditional oligodendrogliomas and oligoastrocytomas, glioblastomas with an oligodendroglial component (GBMO), and WHO grade 2 and 3 astrocytomas. Because Olig genes have a crucial role in oligodendroglial determination, our data could be of help in defining the real spectrum of oligodendroglial tumors.

Astrocytes↗
PubMed2004

Loss of 14q chromosome in oligodendroglial and astrocytic tumors.

Loss of chromosome 14q has been investigated in 142 gliomas. Loss of heterozygosity (LOH) at one or more microsatellite has been found in 8/30 grade II (27%) and 2/21 grade III (10%) oligodendrogliomas, 3/9 grade II (33%) and 5/15 grade III (33%) oligoastrocytomas, 0/9 grade II (0%) and 1/7 grade III (14%) astrocytomas, 11/51 glioblastomas (22%). Two minimal regions were identified on 14q21.2-14q24.3 (between D14S288 and D14S74) and 14q31.3-14q32.1 (between D14S74 and D14S65). Loss of 14q was not correlated to survival, histological grading and subtype or other genetic alterations, except for 1p deletions. Taken together, these data suggest that LOH14q is an early alteration involving 20% of glioma.

Astrocytoma↗
PubMed2004

Palliative care in patients with primary brain tumors.

PURPOSE OF REVIEW: Because patients with primary brain tumors often present severe functional impairment as well as behavioral/cognitive dysfunction, they suffer from greater dependency and hopelessness than other cancer patients. Optimal management should not only focus on symptom relief through medication and physiotherapy, but should also take into account the psychosocial burden of the disease on the patients and their caregivers. This review updates available data on supportive care in patients with brain tumor. RECENT FINDINGS: Recent improvements have been made in the management of several complications of brain tumor: pain, epilepsy, and side effects of antiepileptic drugs; disability and related thromboembolic complications; cognitive disorders of mixed (tumoral and/or iatrogenic) origin; side effects of steroids; fatigue; and psychological consequences of the disease. SUMMARY: Avoiding useless "overtreatment" is the governing idea. A very thorough evaluation of the benefit/risk ratios is needed each time a new treatment is being considered. Brain tumor patients are particularly prone to develop severe side effects, increased fatigue, and cognitive deterioration following apparently minor changes in symptomatic treatments. Care is also needed to avoid useless prolongation of a burdensome situation. Another issue is that patients and their caregivers should benefit from the support of a multidisciplinary team to maintain realistic hopes and to anticipate critical decisions. Finally, guidelines from the literature are proposed to improve physicians' communication skills when treating these patients.

Brain Neoplasms↗
PubMed2004

Molecular changes in gliomas.

PURPOSE OF REVIEW: Despite optimal clinical treatment, the prognosis for gliomas remains poor, and little progress has been observed during the last few years. Meanwhile, understanding of glioma oncogenesis has improved greatly. This review focuses on recent advances in molecular biology of glial tumors, with particular emphasis on lineage markers, genetic mechanisms underlying tumor progression, new diagnostic and prognostic markers, and potential therapeutic targets. RECENT FINDINGS: The question of the cell of origin, illustrated by the evidence of tumor-derived multipotent progenitors, by the animal models of gliomas, and by lineage markers such as Olig1/2 markers, remains unsolved. Genotype/phenotype correlation studies have identified early and late genetic alterations related either to astrocytic or oligodendroglial phenotype. They complement the existing World Health Organization morphologic classification and provide additional prognostic markers such as 1p/19q deletion in oligodendrogliomas. Most of these genetic alterations result in the disruption of three main cellular systems: RB1, P53, and tyrosine kinase receptor pathways. New gene alterations have also been identified in glioma, promoting mitotic signal transduction, cell cycle regulation, apoptosis, angiogenesis, or invasion. Gene and protein profiling has been correlated with outcome. SUMMARY: Management of gliomas, especially oligodendrogliomas with 1p19q deletion, benefits from advances in molecular genetics. A better understanding of the molecular pathogenesis and cellular lineage of gliomas will improve tumor classification and define more reliable prognostic markers. There is a hope that it will also lead to novel targets for therapy.

Antineoplastic Agents↗
PubMed2004

Prognostic value of allelic losses and telomerase activity in meningiomas.

OBJECT: The goal of this study was to examine allelic losses and telomerase activity in meningiomas to determine whether they could be used to predict disease recurrence. METHODS: To identify predictive markers of recurrence, a cohort of high-grade (24 World Health Organization [WHO] Grade II and six WHO Grade III) and low-grade (21 WHO Grade I) meningiomas was investigated for losses of heterozygosity (LOHs) on chromosomes 1p, 9p, 10q, 14q, and 22q, a deletion of CDKN2A, and telomerase activity. Results of molecular analyses were compared with radiological and histological findings and progression-free survival (PFS). Losses of heterozygosity on chromosomes 22q, 1p, and 10q, as well as telomerase activity were related to the WHO histological grades of the lesions (p < 0.01, p < 10(-5), p < 10(-4), and p = 0.002, respectively). In the absence of an LOH on 22q, the other alterations were found infrequently. Overall, the number of molecular alterations was closely related to the histological grades of the lesions (p < 10(-6)). An LOH on 22q occurred much more frequently in convexity or falx (33 [87%] of 38 lesions) than in skull base or spinal meningiomas (four [31%] of 13 lesions) (p < 0.001). The histological grade; Simpson grade; an LOH on chromosome 1p, 9p, or 10q; and telomerase activity were correlated with a shorter PFS time (p < 10(-4), p = 0.02, p = 0.000365, p = 0.022, p = 0.00027, and p = 0.000512, respectively). CONCLUSIONS: On the basis of these data the authors suggest that LOH analysis and a telomerase activity assay could be useful to determine molecular predictors of outcome in patients with meningiomas.

Adult↗
PubMed2003

Oligodendrogliomas: an update on basic and clinical research.

Oligodendrogliomas have been the focus of considerable interest over the past decade, ever since they were recognized as chemosensitive tumors. They were once believed to represent less than 5% of gliomas, but by using expanded criteria, they may well represent up to one third. In fact, morphologic criteria are vague and highly subjective and the histologic diagnosis, therefore, remains highly controversial and unsatisfactory. New oligodendrocytic lineage markers, such as OLIG1/2 gene, will probably help to define the real spectrum of oligodendroglial tumors, which may include a wide variety of tumors with very different prognoses. Recently, genetic markers, and particularly loss of 1p and 19q chromosomes, have been shown to predict both prognosis and response to treatment. There is little doubt that these emerging techniques will be very helpful in clinical practice for refining both classification and therapeutic indications of oligodendroglial tumors.

Animals↗
PubMed2003

Intra-cerebral schwannoma simulating glioma.

An intra-cerebral schwannoma, presenting as a cystic, calcified, enhancing frontal mass, arising in a 52-year-old woman was misdiagnosed as a glioma and treated with radiotherapy. This observation emphasizes the importance of careful histological reexamination of all brain tumors when a discrepancy appears between the initial histological diagnosis and the clinical evolution, in order to recognize rare curable entities and to avoid potentially toxic treatment.

Biopsy↗
PubMed2003

Prognostic factors of CNS tumours in Neurofibromatosis 1 (NF1): a retrospective study of 104 patients.

In addition to multiple peripheral neurofibromas, Neurofibromatosis 1 (NF1) predisposes to CNS tumours. Most of them are pilocytic astrocytomas, arise in children and are located in the optic pathways or in the brainstem. The majority are indolent, but factors predictive of poor prognosis have yet to be identified. Furthermore, the incidence and natural history of gliomas of a higher grade, arising in adults or involving other locations are largely unknown in NF1. In order to address these issues, we performed a retrospective study of 104 patients followed in seven French centres between 1982 and 2000. Inclusion criteria were a diagnosis of NF1, according to the National Institutes of Health criteria, and the presence of a CNS tumour, regardless of type, location or age of onset. The series included 88 children (age range 3 months to 17 years) and 16 adults (age range 19-52 years). The median follow-up was 5.6 years. One hundred and twenty-seven CNS tumours were observed in the 104 patients. Eighty-four (66%) were optic pathway tumours (OPT) and 43 (34%) extra-optic pathway tumours (extra-OPT) (brainstem: n = 21; other locations: n = 22). Twenty-one patients (20%) had multiple CNS tumours. OPT were symptomatic in 50 patients and extra-OPT in 19. Main clinical findings at presentation included visual loss (n = 29; 58%) and precocious puberty (n = 5; 10%) for OPT, increased intracranial pressure (n = 9; 48%) for extra-OPT. Fourteen out of the 27 symptomatic tumours with histology were pilocytic astrocytomas. The overall survival rate was 90% at 5 years (95% confidence interval 82-95%). Extra-optic location, tumour diagnosis in adulthood and symptomatic tumours were independent factors associated with shorter survival time (P < 0.05, Cox model). Radiotherapy for OPT was associated with vascular complications (ischaemic strokes) and growth hormone deficiency in 32 and 46% of patients, respectively. In conclusion, mortality is high in extra-OPT, particularly in adults, whereas OPT are only exceptionally life-threatening. Radiotherapy of OPT is associated with an important morbidity in NF1.

Adolescent↗
PubMed2003

[Standards, Options and Recommendations 2002 for the management of adult patients with intracranial gliomas (summary report)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To define clinical practice guidelines for the management of adult patients with intracranial glioma in collaboration with the Association of French-speaking Neuro-oncologists (Anocef) and the French society of neurosurgeons (SNCLF). These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. The main recommendations concern the place of the surgery, radiotherapy, chemiotherapy, imagery and concomitant medical treatments in the specific treatment strategy of grade III and IV glioma, grade II glioma, gliomatosis cerebri, pilocytic astrocytoma, subependymoma, xanthoastrocytoma, intracranial ependymoma and brain stem glioma.

Adult↗
PubMed2002

Preferential loss of paternal 19q, but not 1p, alleles in oligodendrogliomas.

Portions of chromosomes 1p and 19q, which are frequently deleted in oligodendrogliomas, are subject to genomic imprinting, suggesting that the putative tumor suppressor genes could be monoallelically expressed. The parental origins of 1p and 19q allele losses were determined in 6 cases of pure oligodendroglioma. An equilibrated parental loss (3 maternal and 3 paternal) was found for 1p deletions. In contrast, 19q deletions always occurred on the paternal copy (p = 0.015). In this setting, a cloning strategy based on a search for homozygous deletion or mutation of the remaining allele would be appropriate for identifying the tumor suppressor gene located on 1p but inappropriate for identifying the presumably monoallelically expressed tumor suppressor gene located on 19q.

Alleles↗
PubMed2002

Connexin 43-mediated bystander effect in two rat glioma cell models.

In tumor models, the killing by ganciclovir of a fraction of tumor cells transfected with the thymidine kinase (TK) gene has been shown to induce complete regression of the tumor. The mechanism responsible for this bystander effect is thought to be the diffusion of toxic metabolites or apoptotic signals across gap junctions. Connexin 43 (Cx43) is the major component of astrocyte gap junctions. We investigated the susceptibility of two rat glioma cell lines (CNS1 and C6) to thymidine kinase/ganciclovir, before and after transfection with the Cx43 gene. We report a close correlation between the level of Cx43 expression, the extent of gap junctional communication and the amplitude of the bystander effect. Transfection of C6 cells (which display a weak bystander effect and low levels of connexin) with a Cx43 construct induced a strong bystander effect. Inhibition of gap junction activity by 18-alpha-glycyrrhetinic acid abolished the metabolic interaction between TK(+) and TK(-) cells. This metabolic interaction was also abolished if TK(+) and TK(-) cells were separated by a semipermeable membrane. Surprisingly, the transfection of only one of these two interacting cell types with the Cx43 gene was sufficient to induce a bystander effect, although this effect was weaker than that observed if both TK(+) and TK(-) cells expressed Cx43. Finally, Cx43 expression increased sensitivity to contact inhibition. Overall, our data provide evidence that the restoration of gap junctional communication may potentiate HSV/tk-based cancer treatment and suggest that this strategy may have wider application in cancer therapy.

Animals↗
PubMed2002

Analysis of loss of chromosome 10q, DMBT1 homozygous deletions, and PTEN mutations in oligodendrogliomas.

OBJECT: Chromosomal deletions of 10q and candidate genes such as PTEN and DMBT1 have been thoroughly investigated in glioblastomas but few data specifically address oligodendrogliomas. METHODS: In this study, 39 pure oligodendrogliomas were investigated for loss of heterozygosity (LOH) on 10q, PTEN mutations, and DMBT1 homozygous deletions. The LOH on 10q was found in 19 (48%) of 39 oligodendrogliomas and was closely related to anaplasia (p = 0.02), shorter time to progression (p = 0.0005), and poorer survival (p = 0.035). The DMBT1 homozygous deletions were found in 10 (26%) of 39 oligodendrogliomas but only one PTEN mutation was detected. The LOH on 10q is a strong predictor of survival and could be a valuable prognostic marker in oligodendrogliomas. CONCLUSIONS: Frequent inactivation of DMBT1 contrasting with rare mutations of PTEN may indicate that DMBT1 is preferentially involved in oligodendrogliomas. Nevertheless, the absence of a correlation with survival makes the role of DMBT1 in tumorigenesis still questionable and warrants further investigation.

Agglutinins↗