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N De Tribolet

Publications and source records attributed to N De Tribolet.

35 records · Page 2Linked to original sources

[Immunotherapy of tumors of the central nervous system].

Malignant brain tumors are rapidly fatal and adjunction of chemo- and radio-therapy to surgical treatment has little changed their poor prognosis. The development of basic and clinical research in immunology of brain tumors has lead to new therapeutic strategies: 1) Humoral factors: Monoclonal antibodies (MAbs): alone or conjugated (to toxins, radionucleides or chemotherapeutic agents), MAbs can theoretically recognize antigens expressed by tumor cells and reach this target with high specificity. Large amounts of tumoricidal agents could be given to the tumor with low toxic effects to normal tissues. 2) Cellular factors: LAK cells: (lymphokine-activated-killer-cells) and activated TILs (tumor-infiltrating-lymphocytes) are autologous cytotoxic cells which can be produced by ex-vivo culture techniques and infused to the patient. These are very potent tumor-killer cells in vitro, however their in vivo effect is far less dramatic at the moment. 3) Cytokines: interferons, interleukins and other biological modifiers can act either directly on the tumor cells (cytotoxic effect) or indirectly through the modulation of the host-to-tumor response. 4) Combination of humoral and cellular factors: bispecific monoclonal antibodies are hybrid-molecules built from two different MAbs which can recognize two different targets, usually a tumor antigen on one hand and the T-cell-receptor (T 3) on the other hand. This combination of humoral and cellular effectors can theoretically lead to a preferential binding of effector cells to the tumor. All these new techniques are extensively studied in research laboratories and clinical trials without clear therapeutical benefit for the moment.

Antibodies, Monoclonal↗

Morphology of tyrosine hydroxylase-immunoreactive neurons in the human cerebral cortex.

In freshly fixed biopsies of human cerebral cortex obtained at surgery, immunocytochemical staining with antibodies against tyrosine hydroxylase (the rate limiting biosynthetic enzyme for catecholamines) revealed, in addition to a dense axonal plexus, a population of immunoreactive cell bodies. The neuronal nature of these cells was ascertained by: i) the presence of a rich rough endoplasmic reticulum in the cell body and of synapses on the cell body and dendrites, and ii) the demonstration of the lack of reactivity with the astroglial marker, glial fibrillary acidic protein, in the tyrosine hydroxylase-immunoreactive cells. The tyrosine hydroxylase-immunoreactive neurons were found in all areas of cortex sampled, and were located almost exclusively in the infragranular layers. Most tyrosine hydroxylase-immunoreactive cells were bipolar and were vertically oriented, but a few had a multipolar or horizontal dendritic arbor. The dendrites of these cells were varicose and aspiny, and the axons were very thin. Tyrosine hydroxylase-immunoreactive neurons were reported to be present transiently in the developing mammalian cerebral cortex and only recently in cerebral cortex of mature mammalian brains. Internuncial neurons in the human cerebral cortex containing a catecholamine synthesizing enzyme would be significant, in particular considering that catecholamines are likely to be involved in some major mental disorders.

Adolescent↗

Transforming growth factor-beta 2 down-regulates HLA-DR antigen expression on human malignant glioma cells.

Transforming growth factor-beta (TGF-beta) is known to have a potent inhibitory influence on several immune functions. It has recently been demonstrated that TGF-beta 2 is identical to the glioblastoma-derived T cell suppressor factor (G-TsF). In the present study, human malignant glioma cell lines were incubated with various concentrations of TGF-beta 2. An optimal concentration of 1 ng/ml TGF-beta 2 produced a partial but significant decrease of HLA-DR (class II) surface antigen expression on glioma cells expressing this antigen, as well as decreased levels of HLA-DR-specific mRNA. The surface expression of other HLA-related molecules, such as HLA-ABC (class I) and beta 2-microglobulin, was not influenced by TGF-beta 2. The suppressive effect of TGF-beta 2 on HLA-DR expression, both at the surface antigenic and cytoplasmic mRNA levels, could be completely overcome by adding relatively high concentrations (500 U/ml) of interferon (IFN)-gamma to the culture system. However, TGF-beta 2 inhibited the enhancement of HLA-DR surface expression produced by low concentrations of IFN-gamma on some cells which initially did not express these antigens. These results show that TGF-beta 2 can act as a regulator of HLA-DR antigen expression on human glioma cells.

Antigens, Neoplasm↗

In vivo localisation of radiolabelled monoclonal antibody in human gliomas.

F(ab')2-fragments of the anti-melanoma monoclonal antibody MeI-14 were labelled with 123I for external scanning and with 125I for tissue measurement of radioactivity and injected intravenously into patients scheduled for surgical resection of a glioma. The paired-label study was performed by injecting simultaneously 131I-labelled control (F(ab')2-fragments. The patients were scanned by computerised tomoscintigraphy. After surgery, the activities of 125I and 131I were counted in tumour and normal tissues. The results indicate that there was a low but definite uptake of the antibody in the tumour due to its specificity. The external detection was difficult because of accumulation of antibody fragments in the skull.

Antibodies, Monoclonal↗

Changes in CSF pressure after mannitol in patients with and without elevated CSF pressure.

In view of the current concern that rapid infusion of mannitol might initially aggravate intracranial hypertension, the effects of a mannitol infusion on lumbar cerebrospinal fluid pressure (CSFP) were investigated in 49 patients. The studies were performed when the patients were under general anesthesia prior to elective craniotomy for tumor resection or intracerebral aneurysm clipping. The patients were divided into two groups: 24 patients with normal CSFP (Group I, mean CSFP 10.5 mm Hg) and 25 with raised CSFP (Group II, mean CSFP 20.8 mm Hg). Measurements of CSFP, mean arterial blood pressure (MABP), and central venous pressure (CVP) were made serially during and after the infusion of 20% mannitol (1 gm.kg-1 infused over a 10-minute interval). In both groups, mannitol infusion provoked a fall in MABP and an increase in CVP. An immediate decrease [corrected] in CSFP was observed in Group II, whereas CSFP increased transiently but significantly in Group I. Analysis of the arterial and venous driving pressures which contribute to CSFP suggests that the transient increase in CSFP after mannitol in Group I was partly due to the increase in CVP. The presence of intracranial hypertension may thus alter the CSFP response to arterial and venous pressure changes. Cerebral blood volume (CBV) was measured in dogs in a separate study analogous to the human protocol. The CBV increased approximately 25% over control values after mannitol infusion both in the normal animals and in those with CSFP raised by an epidural balloon. The response of the CSFP to mannitol infusion differed between both groups in a fashion similar to that observed in the human subjects. Thus, differences in CBV changes after mannitol do not account for the difference in CSFP response between normal subjects and those with raised CSFP.

Animals↗

[Epidermal cysts of the cerebellopontile angle].

The authors describe six cases of epidermoid cysts of the cerebellopontine angle. They insist on the progressive development, the variable duration and the polymorphism of the symptomatology. The imaging techniques relevant to diagnosis are reviewed. Among these computerized cisternotomography and N.M.R. are the methods of choice. It is suggested that surgical removal should be total whenever possible because of the risk of recurrence of these cysts but with great caution not to cause a vital or functional damage of the brain stem.

Adult↗

[Endovascular treatment of pure spontaneous dural vascular malformations. Review of 23 cases studied and treated between May 1980 and October 1983].

The authors present 23 cases of pure dural spontaneous vascular malformations (DVM) between 1980 and 1983; among the 23 patients, presented with a sellar DVM, 10 with a torcular DVM and adjacent sinuses, 1 DVM was located at the lamina cribriformis. The history of the patients can be classified into 3 groups: - trauma history (9 patients); - vascular disease (15 patients); - infections history (1 patient). Certain remarkable associations were encountered: 2 cases of multifocal DVM, 3 cases with intracranial aneurysms, 1 case with a brain AVM in an other territory, 1 maxillo-facial AVM. Certain aspects of the symptomatology can be noted: 1 case was in a child of 3 years of age, 2 cases presented during pregnancy, 1 case with premenstrual changes, 2 cases with acute choroidal detachment. Of the 11 patients which had a DVM with cortical venous drainage, 9 were complaining of CNS symptoms and 3 were explored in emergency: 2 for SAH, 1 for acute spontaneous SDH. In this series, following a multidisciplinary decision, the treatment chosen was always endovascular a priori. However it was preceded in one case by surgery at the anterior base of the skull in order to develop a collateral circulation from a reachable artery (for embolization); in an other case, it was followed by surgery to evacuate a compressive SDH, and in an other it was completed by surgery to improve a too proximal embolization. Only once had the internal carotid artery to be occluded to obtain a satisfactory clinical result. One slowly regressive complication was noted following active heparin therapy. No patient has been excluded from this series during that period. With the exception of 1 spontaneous cure, following embolization (s) 13 cases are asymptomatic among which 9 have an anatomical "cure"; 4 cases have an incomplete but significant improvement; 1 patient after a initial good result had recurrent symptoms were stabilized with medical treatment; 2 cases were not embolized for technical reasons, but are asymptomatic. Finally, one died a few days after surgery for evacuation of his SDH. Details of embolic agents and vessels embolized are specified. 5 observations can be made: - The angiographic screening must be complete and must not overlook dangerous vessels which could limit the embolization. - All the vascular compartments of the lesion must be visualized, as all of them do not have to be embolized; the embolic agent has to be radio-opaque and the nidus of the malformation must be reached.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Monoclonal antibodies reactive with glioma cell lines derived from experimental brain tumors.

The production of hybridomas between X63-Ag8.653 myeloma cells and spleen cells from female BALB/c mice immunized with 79FR-G-41 glioma cells is reported. One hundred and six hybridoma clones were obtained secreting monoclonal antibodies (McAbs) against different target cells. Specificity tests (RIA, micro-ELISA) showed that McAbs produced by three hybridoma clones (13GC1, 14BC1, 14FC3) bound 79FR-G-41 glioma cells but did not react with fibroblasts, kidney and brain cells of newborn F344 rats. From the specificity analysis of two McAbs (13GC1, 14BC1) it is evident that these did not only react with 79FR-G-41 cells but also with other glioma cell lines (78FR-G-219, 78FR-G-284, 78FR-G-299 and 78FR-G-344) established from chemically induced rat brain gliomas. These results suggest, in accordance with the findings in human neuroectodermal tumors, the expression of common reactivity antigens in different brain tumors of glial origin. However, the McAbs obtained against experimental rat glioma cells did not recognize glioma cells derived from spontaneous brain tumors of dog or man. Immunofluorescence and immunoperoxidase tests indicate that there is a remarkable heterogeneity among cells of experimental glioma lines with respect to the expression of glioma associated determinants recognized by McAbs. The fact that only a variable number instead of the totality of tumor cells in any asynchronous and uncloned tumor cell population expresses, at a certain time, recognizable antigenic determinants has to be taken into account, particularly if they are considered to be employing McAbs as carrier molecules for diagnostic and therapeutic purposes.

Animals↗

Expression of HLA-DR and common acute lymphoblastic leukemia antigens on glioma cells.

The expression on several established human glioma cell lines of two well-defined differentiation antigens, HLA-DR and the common acute lymphoblastic leukemia antigen (CALLA) has been demonstrated. Rabbit anti-CALLA antiserum and monoclonal anti-Ia antibodies specifically lysed glioma cells in the presence of complement. Absorption of anti-CALLA antiserum and anti-Ia antibodies by glioma cells abolished their cytotoxicity against blasts isolated from a common acute lymphoblastic leukemia. Immunoprecipitation of solubilized glioma cells by monoclonal anti-Ia antibodies revealed two polypeptide chains of 28 and 33 kDa, whereas the anti-CALLA antiserum precipitated a single polypeptide chain of 100 kDa.

Absorption↗

[Pituitary apoplexy].

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Cerebrovascular Disorders↗

Malignant transformation of a spinal cord ganglioglioma--case report and review of the literature.

Gangliogliomas are tumors of mixed glial and neuronal phenotype that usually have a benign clinical course. Rare cases display anaplastic features at the time of first presentation or progress to anaplastic gliomas over extended times. We report on a ganglioglioma of the spinal cord that recurred as a malignant glioma one and a half years after resection. The initial neoplasm was composed of a mixture of well-differentiated ganglionic and astrocytic cells. The recurrent tumor was an anaplastic small-cell glioma. The sole unusual aspect in the initial neoplasm was an abundance of small vessels with calcified walls, which mimicked a vascular malformation.

Adult↗

Immunotherapy of brain tumors.

In the process of malignant transformation, astrocytoma cells display a number of surface antigens not expressed by their normal adult counterparts and which have been identified by monoclonal antibodies and characterized biochemically. These include tumor associated antigens (TAA) such as oncofetal antigens of neuroectodermal origin or oncogene products such as epitopes in the extracellular domain of the epidermal growth factor receptor, as well as major histocompatibility antigens (MHC) of class I and class II. Glioma cells also secrete lymphokines like IL-1 and IL-6. The concomitant expression of TAA and MHC together with the disruption of the blood brain barrier may elicit a humoral or cell mediated immune response from the tumor bearing host as demonstrated by the functional analysis of tumor infiltrating lymphocytes. However this response is extremely weak and obviously inefficient because the tumor cells secrete factors which can inhibit or completely abrogate the immune attack by cytotoxic T cells. Among these factors, TGF-beta 2 and PGE2 are of particular interest since they may explain the generally depressed cellular immune response observed in patients with malignant gliomas. To be efficient any form of immunotherapy will require abatement of these suppressive activities in addition to stimulation of the effector functions.

Antibodies, Monoclonal↗

Immunological markers of brain gliomas.

Immunological markers of human gliomas have been looked for by studying the patient's immune response or by raising heteroantisera against these tumours. More recently, the hybridoma technology has allowed to produce monoclonal antibodies recognizing a single antigenic determinant. This paper describes the production of monoclonal antibodies against human glioma-associated antigens and discusses their possible applications as diagnostic tools.

Antibodies, Monoclonal↗