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K Mokhtari

Publications and source records attributed to K Mokhtari.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Cerebral glioblastomas and systemic metastases].

Glioblastomas are highly malignant but locally invasive tumors. In only rare instances do extra-neural metastasis occur. We report herein 2 cases of such dissemination occurring 9 and 15 month after the initial diagnosis and treatment of supratentorial gliomas. Metastasis involved the lung, the kidney and the liver in one case and the bones in the other case. Both patients died within 3 month after diagnosis of the systemic metastasis despite chemotherapy.

Bone Neoplasms↗
PubMed2000

P18 tumor suppressor gene and progression of oligodendrogliomas to anaplasia.

P18INK4C is a good candidate to be the tumor suppressor gene involved in oligodendrogliomas on 1p32. Loss of heterozygosity on 1p, mutation(s), homozygous deletion(s), and expression of p18 in 30 oligodendroglial tumors were investigated. Loss of heterozygosity on 1p was found in 15 tumors. A p18 mutation was found at an recurrence of an anaplastic oligodendroglioma, but not in the primary, low-grade tumor. No homozygous deletions were found and p18 was expressed in all cases. These results show that p18 alteration is involved in tumor progression in a subset of oligodendrogliomas.

Alleles↗
PubMed2000

Benign recurrence of a cerebellar pilocytic astrocytoma 45 years after gross total resection.

OBJECTIVE AND IMPORTANCE: Cerebellar pilocytic astrocytomas are common benign tumours of childhood and mostly easy to treat because of their location and conformation. Nevertheless, unpredictable recurrence as well as the lack of features to predict the rare malignant changes after first removal, still represent a challenging problem. CLINICAL PRESENTATION: A 54 years old man presented with a recurrence of a cerebellar pilocytic astrocytoma 45 years after complete removal. INTERVENTION: Gross total resection was performed. The pathological examination confirmed the same histological pattern as the first tumour. DISCUSSION: Current opinions about management and recurrence of pilocytic astrocytomas are discussed with a review of the literature.

Adolescent↗
PubMed2000

Frequent loss of 1p32 region but no mutation of the p18 tumor suppressor gene in meningiomas.

After chromosome 22 and NF2 inactivation, the loss of chromosome 1p is one of the most frequent abnormalities encountered in meningiomas. However the putative tumor suppressor gene located on 1p inactivated in meningiomas has still to be identified. We screened 68 meningiomas for LOH on chromosome 22 and 1. We found 34 LOH on the NF2 region on chromosome 22 (50%) and 19 LOH on 1p (28%), 16 being associated with loss of chromosome 22. Partial deletions delimited a candidate region located between D1S234 and D1S2797. The p18INK4C tumor suppressor gene, a member of the genes family coding for inhibitors of cyclin-dependent kinases, is located in this region. To determine whether p18 is involved in development of meningiomas, we performed a mutation analysis of the p18 gene and a search for homozygous deletion in the 19 meningiomas with 1p loss. Sequencing analysis of the p18 gene revealed one polymorphism, but no somatic mutations and no homozygous deletions were found. These results confirm that the loss of chromosome 1p32 is a frequent feature in meningiomas, however the p18 tumor suppressor gene which is located in this region, does not seem to be involved.

Alleles↗
PubMed2000

Overexpression of BCL-2, BCL-X, and BAX in primary central nervous system lymphomas that occur in immunosuppressed patients.

In contrast to primary central nervous system lymphomas (PCNSLs) that occur in immunocompetent patients, most of those that occur in immunosuppressed patients are associated with Epstein-Barr virus (EBV). BCL-2-related proteins either block or promote cell death, forming homo- or heterodimers with each other. LMP-1, EBV latent protein, has been shown to upregulate BCL-2 and BCL-XL. This observation suggests that these proteins may be involved in the transformation process of EBV-infected cells. Twenty-three cases of PCNSLs were studied: 12 of the patients were immunosuppressed, and 11 were immunocompetent. For all cases, we collected clinical information, histologic data, and immunophenotype and tested for the presence of EBV (EBER-1, LMP-1). Apoptosis was assessed by the TdT-mediated dUTP-biotin nick-end labeling method and quantified by image analysis. In three cases, electron microscopy was performed. The BCL-2 family proteins (BCL-2, BCL-X, MCL1, and BAX) and p53 expression were studied by immunohistochemistry on paraffin slides. All cases were classified as diffuse large B-cell lymphomas. PCNSLs in immunosuppressed patients were characterized by EBV association, necrosis, important gliosis, and numerous macrophages. There was no significant difference between the two groups regarding the TdT-mediated dUTP-biotin nick-end labeling staining (P = .08). In contrast, PCNSLs in immunosuppressed patients were shown to express high levels of BCL-2, BCL-X, and BAX in more than 80% of tumor cells in 7, 10, and 11 cases, respectively. In immunocompetent patients, only one case showed a high level of BCL-2 expression in more than 80% of the cells, whereas BCL-X and BAX were overexpressed in two cases. These differences are significant (P < .05). In contrast, there was no significant difference between the two groups in MCL-1 expression. Besides EBV association and necrosis, PCNSLs related to immunosuppression are characterized by an overexpression of BCL-2-related proteins, without dramatically modifying their susceptibility for apoptosis.

Adult↗
PubMed2000

Successful treatment of intracranial gliomas in rat by oligodeoxynucleotides containing CpG motifs.

Phosphorothioate oligodeoxynucleotides with CpG motifs (CpG-ODNs) activate various immune cell subsets and induce production of numerous cytokines. To evaluate whether CpG-ODNs can induce rejection of established tumors, Lewis rats were inoculated intracerebrally with syngeneic CNS-1 glioma cells and subsequently injected with CpG-ODNs into the tumor bed. Although all of the control rats (n = 14) died within 23 days, 88% of the animals (n = 8) treated with a single CpG-ODN injection 5 days after tumor inoculation showed long-term survival (>90 days; P < 0.002). CpG-ODNs increased tumoral infiltration with macrophage/microglial cells, CD8, and natural killer lymphocytes. CpG-ODN-cured animals were further protected against a second tumor challenge. CpG-ODNs had no effect on a s.c. CNS1 tumor in nude mice, which suggested that CpG-ODN is not directly cytotoxic and that immunostimulation is required for the antitumoral effect. These findings suggest that intratumoral injections of CpG-ODNs represent a new immunotherapeutic approach in human gliomas, which overcome the need for the selection and purification of a tumoral antigen.

Animals↗
PubMed1999

Mutational analysis of the PTEN gene in gliomas: molecular and pathological correlations.

The PTEN gene, recently identified on chromosome 10q23, has been proposed to be a candidate tumor suppressor gene inactivated in multiple cancers including glial tumors. We investigated 47 glioblastomas (GBM), 14 anaplastic astrocytomas (AA), 6 non-pilocytic low-grade astrocytomas (LGA), 21 low-grade and anaplastic oligodendrogliomas (O) and oligoastrocytomas (OA), and 3 ependymomas (E) for mutation of the PTEN gene using denaturing gradient gel electrophoresis (DGGE) followed by DNA sequencing. These tumors have been previously screened for loss of heterozygosity (LOH) on chromosome 10q, p53 mutations and EGFR amplification. Overall, PTEN mutations, detected in 14 of 91 tumors, were present in 13 of 47 GBM and 1 of 14 AA. In contrast, mutations were absent in other glioma subtypes (0/30). In all informative cases, PTEN mutations occurred in tumors showing LOH on chromosome 10q, confirming the inactivation of this gene by a 2-hit mechanism. No correlation was observed between the presence of PTEN mutation and p53 mutation and EGFR amplification. Our results indicate that biallelic PTEN inactivation plays an important role in the pathogenesis of high-grade astrocytomas as a late event. Moreover, they suggest that PTEN alterations are equally involved in the 2 glioblastoma pathways defined by the presence of EGFR amplification and p53 mutation. Finally, correlation analysis with clinical data did not show that PTEN mutation was linked to survival of the patients.

Brain Neoplasms↗
PubMed1999

Germline mutations of p53 but not p16/CDKN2 or PTEN/MMAC1 tumor suppressor genes predispose to gliomas. The ANOCEF Group. Association des NeuroOncologues d'Expression Française.

Constitutional DNA from 44 selected patients suspected of being genetically predisposed to develop astrocytic tumors was analyzed for germline mutations of the p53, p16, and PTEN genes. Six constitutional missense mutations of the p53 gene were identified (13.6%), but no mutations of the p16 and PTEN genes were found, suggesting that (1) germline p53 mutations contribute to a small portion of astrocytic tumors, (2) inherited mutations of the p16 and PTEN gene do not predispose to the development of gliomas, and (3) other genes are involved in glioma predisposition.

Amino Acid Substitution↗
PubMed1999

Treatment of meningeal gliomatosis.

To evaluate whether vigorous treatment is beneficial for patients with meningeal gliomatosis (MG) we reviewed the case records of 20 consecutive patients treated for a symptomatic MG in our center. All received systemic or intrathecal chemotherapy and six received additional cranial or spinal radiotherapy. Six patients (30%) achieved a partial response (one low-grade astrocytoma, two anaplastic astrocytomas, one anaplastic oligodendroglioma and two glioblastomas). In these cases, clinical improvement was associated with radiological improvement on CT scan or MRI in five and with a major cerebrospinal fluid improvement in three. Three patients (15%) were stable for 3 months or more and 11 (55%) had progressive disease. Median survival was longer for the responding patients (10 months) than for the other patients (2 months). This study suggests that some patients with MG may benefit from a treatment combining radiotherapy to symptomatic areas and chemotherapy with agents that cross the blood-brain barrier or are delivered directly into the CSF.

Adult↗
PubMed1998

A phase I/II study of herpes simplex virus type 1 thymidine kinase "suicide" gene therapy for recurrent glioblastoma. Study Group on Gene Therapy for Glioblastoma.

Despite extensive surgery for glioblastoma, residual tumor cells always lead to relapse. Gene therapy based on retrovirus-mediated gene transfer of herpes simplex virus type 1 thymidine kinase (HSV-1 TK), which specifically sensitizes dividing cells to ganciclovir (GCV) toxicity, may help eradicate such cells. During glioblastoma surgery, HSV-1 TK retroviral vector-producing cells (M11) were injected into the surgical cavity margins after tumor debulking. After a 7-day transduction period, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by MRI-based relapse-free survival at month 4 and by overall survival. Twelve patients with recurrent glioblastoma were treated without serious adverse events related to M11 cell administration or GCV. Quality of life was not negatively influenced by this treatment. Overall median survival was 206 days, with 25% of the patients surviving longer than 12 months. At 4 months after treatment, 4 of 12 patients had no recurrence; their median overall survival was 528 days, compared with 194 days for patients with recurrence (p=0.03 by the log rank test). One patient is still free of detectable recurrence, steroid free and independent, 2.8 years after treatment. Thus, brain injections of M11 retroviral vector-producing cells for glioblastoma HSV-1 TK gene therapy were well tolerated and associated with significant therapeutic responses. These results warrant further development of this therapeutic strategy in brain tumor, including recurrent glioblastoma.

Adult↗
PubMed1998

Atypical neuronal inclusion bodies in meningioangiomatosis.

A case of meningioangiomatosis not associated with neurofibromatosis 2 in a 24-year-old man is reported. Abundant neurofibrillary tangles and threads, shown by immunohistochemistry and ultrastructural analysis to be similar to those seen in Alzheimer's disease, were found in the residual neuropil. Another lesion consisting of argyrophilic globular inclusion bodies with radial fibrils was found at the periphery. Single and double immunostaining with a panel of antibodies showed similarities between these inclusions and Pick bodies.

Adult↗
PubMed1998

Analysis of the p21 gene in gliomas.

The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.

Alleles↗
PubMed1998

Primary central nervous system lymphomas in 72 immunocompetent patients: pathologic findings and clinical correlations. Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS)

We reviewed 72 primary central nervous system lymphomas occurring in immunocompetent patients. The cases were reviewed for clinical data, histology, immunophenotype, bcl-2 and p53 expression, and Epstein-Barr virus association. Follow-up was available for 40 patients included in the Groupe Ouest Est d'étude des Leucénies et Autres Maladies du Sang (GOELAMS) lymphomes cérébraux primitifs (LCP 88) trial. Each diagnosis, requiring a consensus among at least 3 pathologists, was performed according to the recent Revised European-American Lymphoma classification and equivalents in the updated Kiel classification. Tumors were predominantly classified as diffuse large B-cell lymphomas. There were 3 T-cell lymphomas and 1 Hodgkin lymphoma. The proteins bcl-2 and p53 were expressed in 35% and 16% of the tested cases, respectively. Epstein-Barr virus was not found by in situ hybridization except in the case classfied as a cerebral localization of Hodgkin disease. No significant association was found between subtypes, bcl-2 or p53 expression, and patient survival. From the standpoint of their biologic characteristics, primary central nervous system lymphomas are very similar to systemic diffuse large B-cell lymphomas. In contrast to AIDS-related primary central nervous system lymphomas, primary central nervous system lymphomas are rarely associated with Epstein-Barr virus and in immunocompetent patients they express bcl-2 at a relatively low rate.

Adult↗
PubMed1998

Case report: DNA fragmentation in glial cells in a cerebral biopsy from a multiple sclerosis patient.

Multiple sclerosis is characterized by myelin destruction and oligodendrocyte loss. The neuropathological hallmark of the disease is the presence of demyelinated plaques in the central nervous system. We have recently found a gliotoxic factor in MS cerebrospinal fluid which induces programmed cell death in vitro, in glial cells. Here we show DNA fragmentation and glial cell death in biopsy samples, obtained from a patient who underwent surgery with suspicion of tumor, and whose disease record, including brain autopsy, demonstrated an active multiple sclerosis. We used the in situ TUNEL technique, a method which sensitively detects the DNA fragmentation accompanying programmed cell death in tissue sections, and compatible with classical fixation techniques. We found intense DNA fragmentation in nuclei of glial cells at-or very near-to the site of demyelination. A double labeling technique showed that glial fibrillary associated protein positive astrocytes may undergo programmed cell death in multiple sclerosis.

Astrocytes↗
PubMed1997

High-intensity lesion on T1-weighted MR images in neurofibromatosis type 1: a case of premalignant lesion.

We report a patient with NF1, who was followed up because of an optic glioma and one enhancing lesion presumed to be a pilocytic astrocytoma. T1- and T2-weighted MR images showed also a hyperintense periventricular lesion with no enhancement and no mass effect, of an unsuspected nature. Three years later a glioblastoma multiforme developed at the site of this preceding lesion.

Adult↗