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M Favrot

Publications and source records attributed to M Favrot.

At least 55 records · Page 3Linked to original sources
PubMed1991

Direct involvement of CD7 (gp40) in activation of TcR gamma/delta+ T cells.

In this study we reported that on T cell receptor (TcR) gamma/delta+ cells from three cell lines Peer, MOLT-13 and ICRF-1, the T cell antigen CD7 (gp40) can be directly involved in the activation process. This is shown by a rapid increase in cytoplasmic free calcium after stimulation of these cells with an anti-CD7 monoclonal antibody (mAb). Activation through CD7 was further confirmed by measuring the production of interleukin 2 in ICRF-1 cells stimulated with anti-CD7 mAb. In addition induction of mRNA for tumor necrosis factor (TNF)-alpha and TNF-beta in Peer and for granulocyte-macrophage-colony-stimulating factor in MOLT-13 was observed in these anti-CD7-stimulated cells. The same anti-CD7 antibody was unable to activate TcR alpha/beta+ Jurkat cells or normal resting peripheral blood T lymphocytes. We further showed that normal resting TcR gamma/delta+ cells were likewise activated via the CD7 molecule. TcR gamma/delta+ cells obtained from a patient with acute lymphoblastic leukemia 3 months after autologous bone marrow transplantation were induced to proliferate, as measured by [3H]thymidine incorporation after stimulation with anti-CD7 mAb but not with anti-CD3 mAb. Interestingly TcR alpha/beta+ cells from the same donor tested in parallel were not stimulated by anti-CD7 but by anti-CD3 mAb. In essence these findings contribute to the idea that on TcR gamma/delta+ cell, the CD7 antigen could play an important role during T cell differentiation.

Antibodies, Monoclonal↗
PubMed1991

Burkitt's lymphoma: a model for clinical oncology.

Burkitt's lymphoma, a pathological entity initially described in Africa, is the most common childhood lymphoma in western countries and represents approximately 5% of all adults lymphomas. This high grade small non-cleaved diffuse lymphoma is a model with which to study the relations between cancer and viruses, the chromosomes and the genes. Burkitt's lymphoma is also a model for clinical research which allows evaluation of the dose effect concept with chemotherapy and the role of megatherapy with autologous bone marrow rescue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Expression of P-glycoprotein restricted to normal cells in neuroblastoma biopsies.

Immunohistological detection of P-glycoprotein (P-gp) with monoclonal antibody C219 was performed on serial sections of 37 neuroblastoma specimens representative of the different forms of the disease, from stage 1 ganglioneuroma to stage 4 neuroblastoma. Malignant cells, irrespective of their degree of maturation varying from neuroblasts to ganglion cells, were negative on all specimens. The expression of P-glycoprotein was detected in nine specimens, but it was restricted to normal cells within the tumour. In four specimens, C219 reacted with normal infiltrating cells in the stroma (i.e. monocytes, histiocytes or fibroblasts) representing 5 to 10% of the total population within the section; in three specimens, the residual adrenal gland was strongly positive, and in two ganglioneuromas, a weak reactivity of C219 was observed on a few satellite cells and schwann cells. Three of 15 biopsies obtained at diagnosis contained normal P-gp positive cells: two were classified as stage 1 ganglioneuromas; one was a typical stage 4 composite tumours with positive histiocytes and fibroblasts in the well-differentiated counterpart. Six of 22 biopsies obtained after patients had received our current protocol of chemotherapy contained normal P-gp positive cells: five were partially differentiated and necrotic under the effect of chemotherapy; only one positive specimen was classified as undifferentiated neuroblastoma. Among negative specimens from previously treated patients, one was obtained from a patient in relapse after high-dose chemotherapy and ABMT, two were obtained from patients who had not responded to induction therapy, and six from patients in partial remission after induction therapy. The clinical evolution was very similar in both groups of patients with P-gp negative or positive biopsies. These findings suggest that the quantitative assessment of MDR RNA by northern blotting on fresh homogenates is likely to overestimate its expression on neuroblastoma cells, and that the mechanism of chemoresistance in widespread neuroblastoma is less likely to be associated with P-gp expression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Acute renal failure with preserved renal plasma flow induced by cancer immunotherapy.

Adoptive immunotherapy in patients with advanced cancer produces significant regression of metastatic disease in selected patients, but it is complicated by severe side effects. Prevention of these complications is still limited because their precise mechanisms remain unknown. For this reason we have investigated renal function and hemodynamic parameters in 16 patients with renal cell carcinoma before and during treatment with a combination of high doses of both recombinant interleukin-2 (rIL2) and recombinant alpha-interferon. After patients had received three injections of combined immunotherapy, there was a decrease in mean blood pressure (-20%), glomerular filtration rate (-25%), urine output (-50%), and fractional sodium excretion (-0.8%). This was associated with an increase in heart rate (+30%), plasma creatinine level (+30%), fractional potassium excretion (+14%) and microalbuminuria (+130%). However, renal plasma flow remained constant. The increment in microalbuminuria may reflect an alteration of glomerular capillary permeability. The reduction in GFR may be accounted either for a decrease in efferent to afferent arteriolar resistance ratio, leading to a decrease in glomerular capillary pressure, or for a decrease in ultrafiltration coefficient, or both. Nonsteroidal antiinflammatory drugs, such as ketoprofen, used to minimize side effects, could considerably worsen renal function and should be avoided in patients treated by rIL2. Our results bring new insights into the pathogenesis of functional acute renal failure and provide a rational basis for the use of vasopressors in the treatment of cytokine-induced acute renal failure.

Acute Kidney Injury↗
PubMed1990

Autologous bone marrow transplantation in pediatric solid tumors.

During the last 5 years massive chemotherapy and autologous bone marrow transplantation have been increasingly explored in the treatment of pediatric solid tumors, mainly for neuroblastoma, Ewing's sarcoma, rhabdomyosarcoma, Wilms' tumor, germ cell tumors, osteosarcoma, and retinoblastoma. Although the disease course could be changed successfully in most instances, the long-term survival has not yet been improved much over the best available conventional treatments. Despite this, in responding relapsed patients this approach seems promising and may represent the only chance of cure. New and better induction regimens are needed.

Adolescent↗
PubMed1990

Effect of in vivo therapy with a CD8 monoclonal antibody on delayed engraftment after autologous bone marrow transplantation.

Very long delay to engraftment (or non-engraftment) was observed in eight patients presenting common immunological features, i.e. excess of blood and bone marrow lymphocytes coexpressing CD8 and CD57 (HNK1) antigens. They were therefore treated by CD8 immunotherapy. Such treatment induced a complete clearance of CD8+, CD57+ cells from the blood and bone marrow in five cases, a partial clearance in one, the absence of clearance in one and a modulation in the last case. No toxic side effects were observed. Platelet recovery was observed in only two patients, but long-lasting granulocyte recovery was seen in six of the cases from day 6 to day 30 after the beginning of CD8 infusion (median = 17 days).

Adolescent↗
PubMed1990

[Role of massive chemotherapy and bone marrow graft in the treatment of non-Hodgkin's lymphoma].

Intensive chemotherapy and high dose chemotherapy with bone marrow transplantation are 2 complementary therapeutic procedures for non Hodgkin's lymphomas. In children, indications for BMT in NHL are limited to patients who fail to achieve complete remission and for patients in sensitive relapse. In adults, the role of BMT is also recognized for patients who fail to achieve remission with initial therapy. The advantage of either conventional regimens or massive therapy with BMT for patients with poor prognostic criteria is still under evaluation (LNH 87 protocol). The PARMA protocol tests, in a multicenter randomized study, the value of BMT for patients in sensitive relapse. Results of BMT for patients with refractory NHL and resistant relapse, remain poor. The role of BMT in low grade lymphomas is debatable. The trials for evaluation of massive chemotherapy and BMT in NHL will contribute to defining the potential role of this therapy in France: a potential 1,000 cases per year may be treated by this method.

Adult↗
PubMed1990

[Adoptive immunotherapy with interleukin 2 in oncology].

Forty-seven patients with renal carcinoma were included in first line or rescue protocols of immunotherapy including IL2 alone or in association with LAK cells, INF alpha or TNF. The toxicity was mild and the mortality was 2% (1 patient). The response rate was 26%. Nineteen children with neuroblastoma received IL2 either alone or in combination with LAK cells. The morbidity and mortality were higher in patients with end stage disease who had previously received high dose and prolonged chemotherapy. In contrast, the toxicity was mild and transient in patients treated in the months following autologous bone marrow transplantation. The only complete response observed was in 1 child treated with IL2, 4 months after high dose chemotherapy and ABMT. Immunological analysis showed that the immunomodulatory effect of IL2 is very different depending on whether IL2 is used alone or in combination with other cytokines; moreover, the biological effect of IL2 is dependent on the immunological status of the patients prior to IL2 therapy.

Adenocarcinoma↗
PubMed1990

Lectin-binding properties of Burkitt's lymphoma cell lines: application to bone marrow purging.

The efficacy of binding of several lectins to different Burkitt's lymphoma (BL) cell lines was investigated. Soybean agglutinin (SBA), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and Sambucus nigra agglutinin (SNA) bound strongly to all BL cell lines. Because SBA has been used safely in clinical bone marrow transplantation (BMT) as part of the procedure for T-cell depletion and hence does not bind to the stem cells, we chose this lectin to establish a model for purging BL cells from human bone marrow. Using a two-step purging procedure with tumor cell agglutination by SBA in solution, a 2-log depletion could be accomplished. Using SBA-coated magnetic beads, we could improve BL cell depletion to greater than 4 logs. Because SBA seems to have a broad specificity for BL cells with concomitant enrichment in hematopoietic progenitor cells, the use of SBA-coated magnetic beads could be of interest for autologous BMT for lymphomas as well as other hematological malignancies and solid tumors with positive binding to SBA.

Agglutination↗
PubMed1990

Hormonal and metabolic effects of chronic interleukin-2 infusion in cancer patients.

Interleukin-2 (IL-2) is secreted during the immune response to trauma, sepsis, and transplant rejection. Its role in the development of the metabolic abnormalities observed in these circumstances is not well defined. We studied the clinical, hormonal, and metabolic response to a 5-day IL-2 infusion (3 x 10(6) U/m2/day) of nine patients with metastatic renal carcinoma. IL-2 induced systemic manifestations after a latent period of 4 h (fever, tachycardia) or 8 h (hypotension). These manifestations persisted until the end of the infusion. Insulin levels were not modified. Among the stress hormones, cortisol increased at the onset of fever and tachycardia, whereas the rise in catecholamines occurred later (24 h) and appeared more as a response to the development of hypotension. The only metabolic effects observed were a late (third day) rise of lactate and a late and transient (third to fourth day) decrease of glycerol and nonesterified fatty acids. These metabolic modifications were temporally related to the development of hypotension and result more likely from low tissue perfusion rather than from a direct or hormone-mediated effect of IL-2.

Adult↗
PubMed1989

A phase-II study of adoptive immunotherapy with continuous infusion of interleukin-2 in children with advanced neuroblastoma. A report on 11 cases.

Nine children with poor prognosis neuroblastoma have been treated by continuous infusion of IL-2 and autologous LAK cells, as described previously by West et al. in adult patients. Six patients were in relapse after high-dose chemotherapy and autologous BMT and three presented with primary refractory disease after conventional therapy. Although patients were very young (median age 6 years; average weight 17 kg), infusion of IL-2, cytapheresis and reinjection of LAK cells appeared feasible with the usual and transient complications observed with IL-2. Haematological toxicity, although reversible, was more important than usually described and due to the presence of bone-marrow metastases in 8 of the 9 patients. Life-threatening toxicity was observed in only one of the admission centres and was probably due to the rapid reinjection of a very large number of activated cells. Two patients presenting with very active disease after high-dose chemotherapy and autologous or allogeneic BMT received IL-2 alone, at 120 days and at 90 days after the graft. The reactivation of grade-II GVHD was the major complication in the patient treated after an allograft, whereas no BMT-related toxicity was observed in the patient treated after the autologous BMT. Immunological modifications induced by IL-2 were very different between these patients. As expected, a preferential outgrowth of NK cells with both NK and LAK activity was observed in the patient treated just after the autograft. In contrast, in the patient treated after an allograft and in the 9 patients in relapse, T lymphocytes remained the major mononuclear cell population with a very large excess of CD8+ T cells. All patients progressed after the first induction cycle with the exception of the only patient treated after autologous BMT who reached a very good partial remission with disappearance of the local tumor and bone metastases. Although very preliminary, these data clearly show that the efficacy of IL-2 largely depends on the patient's immunological status with the optimal effect being observed when IL-2 is given in the first few months following an autograft.

Bone Marrow Transplantation↗
PubMed1989

Bone marrow metastases in small cell lung cancer: detection with magnetic resonance imaging and monoclonal antibodies.

The detection of bone marrow involvement might be of prognostic value and may influence therapeutic decisions in small cell lung cancer. By unilateral bone marrow aspiration and biopsy, evidence of bone marrow metastases is seen in 15-30% of patients with this disease. Since magnetic resonance imaging of the lower body and immunostaining with monoclonal antibodies have recently been shown to be very sensitive detection methods, we investigated the value of these two techniques in detecting bone marrow involvement in 35 consecutive patients with small cell lung cancer. The results were compared to those obtained with conventional cytohistological analysis. In all cases when cytology and/or bone marrow biopsy were positive, monoclonal antibodies immunostaining and magnetic resonance imaging also detected malignant cells. Furthermore, evidence of bone marrow involvement was shown with magnetic resonance imaging and/or immunostaining in 10 of 26 cases (38%) where routine procedures were unable to detect malignant cells. In one of these 26 patients, magnetic resonance imaging and immunostaining provided the only evidence of metastatic disease. These data suggest that the rate of bone marrow metastases is underestimated by routine procedures. Further investigation is needed to determine whether or not these new non-invasive methods have prognostic value or affect therapeutic choices in small cell lung carcinoma.

Antibodies, Monoclonal↗
PubMed1989

[Cytokines and their receptors networks: biology and therapeutic possibilities].

Cytokinins are biological proteins which permit the transmission of signals from one cell to another. These proteins are secreted by groups of specialized cells and are fixed on specific receptors on the surface of responding cells. However, since receptors may be widely distributed, and since the activation of a cell usually permits the release of other cytokinins and a succession of reactions, cytokinins have pleiotropic effects. Cloning of the genes encoding for these cytokinins and their obtention on a large scale by genetic recombination techniques have allowed a better understanding of their biological characteristics and their use in therapy. This cytokinin network is particularly wide in the hematopoietic and in the immune systems. In the present study, we describe the biological properties of the main interleukins and hematopoietic cell growth factors, together with their therapeutic applications, particularly in hemato-oncology.

Biological Factors↗
PubMed1989

Analysis of parameters for maximal in vitro proliferation and activation of lymphokine-activated killer cells (LAK).

In 15 patients (11 adults, 4 children) who received IL-2 and LAK cell therapy, we analyzed the different culture conditions which could either improve LAK cell activation and proliferation or which could simplify the procedure. Each parameter was assayed on a large scale and compared to standard culture conditions. Indomethacin had no effects, either positive or negative, on proliferation and activation of the cells. Culturing with 10% AB serum increased proliferation but did not modify total lytic activity compared to 2% AB serum. When cells were cultured in a medium with 2% autologous plasma obtained before any treatment, their proliferation was similar to that obtained in medium supplemented with 2% AB serum but the LAK activity was significantly higher. Autologous plasma obtained at day 8 of treatment (48 h after the first cycle of IL-2 and the day of the first cytapheresis) gave similar results to 2% AB serum. None of the 12 patients showed negative effects suggesting the presence of suppressive factors in the sera. Culturing with autologous plasma in clinical trials will lead to a 25% decrease in the total cost of culture and suppress the risk of viral contamination. Excess of granulocytes in the culture (greater than 30%), if the total nuclear cell concentration did not exceed 3 . 10(6) per ml, induced a better proliferation of mononuclear cells without modification of the activation. These results could be due to the liberation of factors by polynuclear cells, or to the loss during elimination of the granulocytes by the Ficoll separation of cells with similar density supporting LAK activity.

Adult↗
PubMed1988

Immunocytochemical detection of neuroblastoma cells infiltrating clinical bone marrow samples.

To evaluate the feasibility and clinical usefulness of immunocytochemical detection of bone marrow metastases in neuroblastoma, we studied bone marrow samples from patients undergoing intensive therapy, followed in the majority of cases by autologous bone marrow rescue. Two monoclonal antibodies were used in an indirect immunoenzymatic assay to test 384 samples collected from multiple bone marrow sites during 79 staging procedures in 48 patients. Of 578 immunocytochemical tests, 59 (10%) yielded non-evaluable results. Analysis by individual bone marrow sites showed an agreement between cytological and immunocytochemical examinations in 276 of 309 (89%) evaluable tests with 5 A7 and in 179 of 210 (85%) with UJ 13 A. Infiltration by neuroblastoma cells was reported in 9% of samples by cytology, in 6% by immunochemistry with 5 A7 and in 16% with 13 A. Analysis of results by staging demonstrated agreement between cytological examination and immunocytochemical detection with both monoclonal antibodies in 60 of 75 (80%) evaluable stagings. Bone marrow metastasis was detected by cytology in 22% of stagings, by immunochemistry with 5 A7 in 23%, with UJ 13 A in 25%. Detailed analysis of discordant results revealed that they were related partly to bone marrow sampling variability associated with focal and minimal metastasis of neuroblastoma cells. These data suggest the clinical usefulness of immunocytochemical detection as a complementary test to cytological examination for accurate evaluation of bone marrow infiltration in patients with disseminated neuroblastoma.

Antibodies, Monoclonal↗
PubMed1988

International criteria for diagnosis, staging, and response to treatment in patients with neuroblastoma.

Neuroblastoma is one of the most common tumors in childhood. However, it often has been difficult to compare clinical and laboratory studies of this disease due to a lack of uniform criteria for diagnosis, staging, and response. An international group of conferees addressed each of these issues and reached a consensus. Specific criteria for making a diagnosis of neuroblastoma are defined. A new neuroblastoma staging system is proposed that takes into account the most important elements of current but incompatible systems. Finally, criteria for response to treatment are standardized. The criteria proposed herein represent an international consensus of essentially every major pediatric oncology group or organization in the United States, Europe, and Japan. The staging system should be referred to as the International Neuroblastoma Staging System, and the response criteria as the International Neuroblastoma Response Criteria. Implementation of these criteria will greatly facilitate the comparison of clinical and laboratory studies by different groups and countries. Furthermore, these criteria should serve as a foundation on which future modifications or improvements can be based.

Humans↗