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Biomedical subjects

E Tartour

Publications and source records attributed to E Tartour.

At least 55 records · Page 3Linked to original sources
PubMed1995

A transforming growth factor beta-like immunosuppressive factor in immunoglobulin G-binding factor.

Immunoglobulin G-binding factors (IgG-BF), which are produced by cells of the immune system, inhibit antibody production. In this paper, we show that transforming growth factor-beta (TGF-beta) suppresses secondary in vitro anti-sheep red blood cell responses of mouse splenocytes and lipopolysaccharide- or anti-IgM-stimulated mouse B cell responses in a way similar to, and with the same kinetics as, rodent IgG-BF. Moreover, the immunosuppressive activity of IgG-BF was totally neutralized by polyclonal and monoclonal anti-TGF-beta antibodies and it eluted with TGF-beta by gel exclusion chromatography, suggesting that a TGF-beta-like immunosuppressive factor is present in IgG-BF. We also show that TGF-beta behaves as an IgG-BF since it binds to insolubilized IgG, but not to insolubilized F(ab')2 or bovine serum albumin. Altogether, the data support the concept of a biological role for TGF-beta in the IgG-mediated negative feedback of antibody responses.

Animals↗
PubMed1995

Multicolor flow cytometry analysis of blood cell subsets in patients given total body irradiation before bone marrow transplantation.

PURPOSE: Bone marrow transplantation has often been closely linked with accidental or intentional therapeutical irradiation. In both situations, study of the radiosensitivity of human blood cell subsets is of interest. Using one-color flow cytometry analysis of B lymphocytes, T cell subsets, and natural killer cells, we previously reported that lymphocyte subsets exhibit equal radiosensitivity. Taking advantage of recent developments in the knowledge of leukocyte differentiation antigens and flow cytometry technology we undertook a study of blood cell subsets to search for rare populations exhibiting different radiosensitivity. METHODS AND MATERIALS: Thirty patients, who were delivered a 12 Gy fractionated total body irradiation as part of their conditioning regimen before transplantation for malignant disorders, were studied using multicolor flow cytometry. RESULTS: T and B lymphocytes showed a sharp, radiation-induced decrease, with the B lymphocytes (cluster of differentiation (CD) 19+) being the most sensitive. When analyzed by multicolor flow cytometry, all major lymphocyte subsets appeared equally sensitive to the in vivo irradiation; that is, CD3+4+45RO+, CD3+4+45RA+, CD3+4+8-, CD3+4-8+. Therefore, all major lymphocyte subsets sharing the helper phenotype (naive or memory) and the cytotoxic phenotype appeared equally sensitive to in vivo whole body irradiation. In parallel, the CD34+ cell subset remained basically unchanged after whole body irradiation. Finally, the CD3-, 56+, 16+ natural killer cell subset was relatively radioresistant (91 and 74% of its initial value, after 2 and 4 Gy, respectively) as compared to other lymphocyte subsets. CONCLUSION: Our study provides evidence that T and B cell subsets seem to be highly radiosensitive in vivo. The CD34+ progenitor/stem cells and NK cells seem to be more radioresistant. This latter result might provide clues to the understanding of the pathophysiogeny of radiation-induced aplasia and of the engrafment/rejection process following bone marrow transplantation.

Adolescent↗
PubMed1995

Variable expression of CD3-zeta chain in tumor-infiltrating lymphocytes (TIL) derived from renal-cell carcinoma: relationship with TIL phenotype and function.

It has been reported that in mice and in humans, tumor-infiltrating lymphocytes (TIL) may exhibit a defect in CD3-zeta-chain expression. Therefore, the level of CD3-zeta was analyzed in TIL derived from patients with renal-cell carcinoma, and its correlation with TIL phenotype and function was assessed. We identified 4 out of 13 tumor-infiltrating lymphocytes derived from renal-cell carcinoma, with a significant decrease in CD3-zeta-chain expression as compared with control peripheral-blood lymphocytes. This defect was never found after culturing TIL with IL2. In one case, the low expression of zeta chain observed in TIL on day 0 was reversed when TIL were cultured with IL2. The zeta-chain level did not seem to predict the growth of TIL in response to IL2. All the TIL, irrespective of the level of zeta-chain expression, exhibited lower proliferative response when stimulated with PHA or anti-CD3 MAb in comparison with normal peripheral-blood mononuclear cells. Nevertheless, in this limited series of patients, a correlation was observed between the level of zeta-chain expression and T-cell infiltration (p = 0.02). After TIL stimulation with PHA or anti-CD3, in contrast to IL2 or IFN-gamma production, a trend towards a relationship between TNF alpha induction and the level of zeta-chain expression was observed.

CD3 Complex↗
PubMed1995

Prognostic value of cytokine and soluble Fc gamma receptor assays in oncology.

The clinical course of a cancer is influenced by the interaction of tumour cells with the patient's immune system. It is thus conceivable that immunological parameters may be used as markers of prognostic or predictive value. We report here that increased serum levels of IL-6 is a signal of poor prognosis and predicts unresponsiveness to immunotherapy in patients with metastatic melanoma. In cervical cancer, IL-6 produced by infiltrating macrophages is a marker of invasive cancer. In patients with multiple myeloma, the plasmatic levels of soluble Fc gamma receptors are markers of the disease, sCD16 being drastically decreased and sCD32 being slightly increased.

Cytokines↗
PubMed1995

Lack of efficacy of low-dose subcutaneous recombinant interleukin-2 and interferon-alpha in the treatment of metastatic renal cell carcinoma.

OBJECTIVE: To evaluate the efficacy and toxicity of subcutaneous immunotherapy using a combination of recombinant interleukin-2 (r-IL2) and interferon-alpha (IFN-alpha) for the treatment of patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Initially a maximum of 45 patients with advanced RCC were to be included in the study, according to a Fleming three-stage procedure. To be included patients had to have measurable metastasis. Of a potential 45 patients with advanced RCC, 15 patients were included in the study (10 men and five women, mean age 51 years, range 25-69). From the first week of treatment r-IL2 was given subcutaneously on day 1 to 5, at 18 x 10(6) units once a day and then 9 x 10(6) units once a day for the following 5 weeks. IFN-alpha was given three times a week for the last 5 weeks. Minimum follow-up was 6 months. RESULTS: All patients initially underwent radical nephrectomy. Seven patients were found to have metastases at the time of diagnosis. All patients received ambulatory therapy, except for the first 5 days of treatment. Overall, 80% of the patients received more than 75% of the complete dose of r-IL2. One patient suffered toxicity greater than the World Health Organization (WHO) grade 2 (neutropenia). No patient had a complete or partial response, two patients had a minor response, two patients had stable disease and 11 patients had disease progression. CONCLUSIONS: Subcutaneous r-IL2 and IFN-alpha had no beneficial effect on the first 15 patients and the study was discontinued, in accordance with the Fleming rules. The dose, administration and combination of r-IL2 and IFN-alpha may explain the lack of efficacy. Other studies have shown that low doses of r-IL2 are not effective and the superiority of the combination of r-IL2 and IFN-alpha has not been proven. Therefore, a high dose of r-IL2, in association with other cytokines, chemotherapy and adoptive immunotherapy, may be the only way to improve the response rate of metastatic RCC.

Adult↗
PubMed1995

[Immunotherapy of malignant diseases].

Cancer immunotherapy has been carried out since the early fifties and first involved nonspecific system (BCG, Corynebacterium parvum, levamisole...). More recently, the production of cytokines as interferons or interleukin 2, the introduction of monoclonal antibodies have allowed a new development to cancer immunotherapy. Nevertheless, these new approaches have to be considered as a step in the biological therapy of cancer.

Animals↗
PubMed1995

[Endocrine involvement in immunotherapy].

Thyroid dysfunction and abnormalities in corticosteroid regulation were observed after clinical use of cytokines (IL2, IFN alpha), molecules with immunostimulating properties. Interleukin 2 administration induces hypothyroidism often associated with anti-thyroglobulin and anti-thyroid microsomal antibody. All these features recall Hashimoto's thyroiditis. Frequency of thyroid dysfunction during immunotherapy varies according to authors between 20 and 40 percent of all patients treated. A correlation between thyroid dysfunction and response to IL2 therapy was reported. Hypothyroidism and hyperthyroidism with development of anti-TSH receptor antibody are observed after IFN alpha administration. An auto-immune aetiology of these thyroid side effects was suggested because fine needle aspirates of the thyroid of these patients, when available, revealed a mixed cellular infiltrate with lymphocytes and histiocytes and immunocytochemical staining showed strong HLA-DR expression of all thyrocytes. Involvement of lymphokine activated killer (LAK) or direct effect of cytokines on thyroid are also possible. After intravenous injection of IL2, a marked increase in ACTH levels occurred, peaking at 4 hour with a comparable peak in cortisol level at 5 hour. Expression of IL2-Receptor in pituitary cells suggests a direct action of IL2 on anterior pituitary. Nevertheless, indirect action of IL2 via induction of other cytokines or possible secretion of ACTH by activated lymphocytes, cannot be ruled out. Testosterone serum levels decreased significantly after IL2 or IFN alpha administration. It is noteworthy that these endocrine effects induced by cytokines may modulate the clinical efficacy of these substances underlying the bi-directional communication between the immune and endocrine system.

Adrenal Cortex Hormones↗
PubMed1994

Analysis of interleukin 6 gene expression in cervical neoplasia using a quantitative polymerase chain reaction assay: evidence for enhanced interleukin 6 gene expression in invasive carcinoma.

Interleukin 6 (IL-6) is a multifunctional cytokine which has recently been shown to act in vitro as a growth factor for cervical carcinoma cell lines. This prompted us to measure IL-6 gene expression using a new quantitative polymerase chain reaction assay in 13 invasive cervical cancers, 5 cases of cervical intraepithelial neoplasia, and 2 normal cervix. A significant increase in the expression of the IL-6 gene in invasive cervical carcinoma as compared to cervical intraepithelial neoplasia and normal cervix was demonstrated (P < 0.05). Unlike IL-6, the expression of other cytokine genes such as gamma-interferon was not correlated with any particular cervical histological lesion. Immunohistochemical analysis identified IL-6 protein only on stroma cells which, based on morphological criteria, most likely belong to the macrophage lineage. This was reinforced by the correlation observed between IL-6 gene expression and macrophage tumor infiltration (P < 0.007). No IL-6 immunostaining of cervical tumor cells was shown. Therefore this study confirms, in vivo, that IL-6 may play a role in the pathogenesis of carcinoma of the uterine cervix since its increased expression is associated with advanced neoplastic cervical lesions. In contrast to in vitro studies, the stromal origin of IL-6 suggests that this cytokine may modulate tumor cell proliferation by a paracrine rather than an autocrine mechanism.

Base Sequence↗
PubMed1994

Natural and recombinant soluble low-affinity Fc gamma R: detection, purification, and functional activities.

Studies on the identification, cloning, and biochemical characterization of natural and recombinant human and mouse low-affinity soluble Fc gamma R (sFc gamma R) have been developed using various methods. RT-PCR and/or biochemical analyses have demonstrated that low-affinity sFc gamma R (i) are generated by enzymatic cleavage of membrane-associated receptors or by an alternative splicing of the transmembrane region encoding exon and (ii) comprise only the extracellular domains or these domains plus the intracellular region of the membrane-associated molecules, respectively. Functional studies indicated that recombinant sFc gamma R bind mouse and human IgG subclasses with a binding profile identical to that of their membrane counterparts and inhibit Fc gamma R-mediated functions such as immune complex binding or ADCC. In addition, it has been demonstrated that a mouse recombinant truncated sFc gamma RII inhibits antibody responses to T-dependent antigens as well as B-cell proliferation and that a human recombinant truncated sFc gamma RIIIB blocks the Ig production by activated human peripheral blood mononuclear cells. Finally, different immunoassays devised to detect and quantitate circulating sFc gamma R showed that sFc gamma R serum levels vary in circumstances such as injections of protein antigens, in parasitic infections, in tumor-bearing mice, in patients with multiple myeloma (MM), or upon infusions of IgG or Fc gamma fragments in MM or immune thrombocytopenic purpura patients. The use of recombinant sFc gamma R, as well as the availability of monoclonal and polyclonal antibodies directed against different regions of these molecules, makes it possible to characterize further the biological effects of sFc gamma R and their biochemical and immunochemical characteristics, as well as to define their putative ligands on cell membranes.

Amino Acid Sequence↗
PubMed1994

Anti-cytokines: promising tools for diagnosis and immunotherapy.

Anti-cytokines belong to a new family of biological response modifiers which interfere with the biological functions of cytokines. An imbalance between cytokines and natural anti-cytokines may represent an important factor to explain the pathogenesis of some human diseases. Indeed, dysregulation of anti-cytokine serum levels was observed in cancers and auto-immune and infectious diseases. It was sometimes associated with disease activity and in some circumstances they may help to predict clinical response to treatment. Control of disease activity in septic shock and auto-immune diseases was demonstrated after administration of anti-cytokines such as soluble TNF receptors and IL1ra inhibitors. Therefore these agents are promising tools for diagnosis and immunotherapy.

Autoimmune Diseases↗
PubMed1994

Detection of GM-CSF in the sera of children with Langerhans' cell histiocytosis.

GM-CSF induces proliferation and activation of Langerhans' cells in vitro. The density of Langerhans' cells in human tumours is correlated to the in situ density of GM-CSF, and intradermal injection of GM-CSF induces local accumulation of Langerhans' cells. Therefore, we investigated the presence of GM-CSF in the sera of children with Langerhans' cell histiocytosis (LCH). We detected GM-CSF in the sera of all children with disseminated and active LCH, but not in the sera of patients with localized (i.e. bone) LCH. These results suggest that GM-CSF level is related to extent and the activity of LCH.

Adolescent↗
PubMed1994

Phenotypic and functional analysis of tumour-infiltrating lymphocytes from patients with renal cell carcinoma.

Twenty renal cell carcinomas were cultured in the presence of 200 IU/ml of recombinant interleukin-2; tumour-infiltrating lymphocytes (TIL) developed in 70% of cases; the phenotypic profile was heterogeneous in 11 TIL tested on day 30: 4 were mostly CD8 positive, 4 mostly CD4 and 3 showed CD4-CD8-CD56 mixed phenotypes. The cytotoxic activity was also heterogeneous, and no TIL developed a tumour-specific cytotoxic activity. The phenotypic profile and cytotoxic activity were also tested after thawing, and this study demonstrated that TIL can be frozen at the time of the nephrectomy, then thawed and cultured for the purposes of therapeutic trials when metastases appear. The differences between TIL derived from renal cell carcinoma and TI1 derived from melanoma are discussed.

Carcinoma, Renal Cell↗
PubMed1994

[CD4 TIL (Tumor Infiltrating Lymphocytes) induce complete response in patients treated with IL-2 (Interleukin-2). Preliminary study].

This study analyzed clinical response induced by TIL in patients with renal cell carcinoma previously treated by interleukin-2. Six patients (4 men, 2 women, mean age 44.3 years) with measurable metastatic localizations have been treated by TIL reinjection (0.02 to 7.6 x 10(10) cells). TIL phenotype was a combination of CD4 and CD8 in 3 patients, predominantly CD4 in two patients and predominantly CD8 in one patient. Previous treatment by interleukin-2 induced one partial response, 2 stabilizations of the disease and 3 tumoral progressions. TIL led to an amelioration for 4 patients: 2 were in complete response, 2 were stabilized and 2 had tumoral progression and decreased. This study shows that CD4 TIL may improve an initially response induced by IL-2 therapy.

Adult↗
PubMed1993

Immunohistochemical study of adrenocortical carcinoma. Predictive value of the D11 monoclonal antibody.

BACKGROUND: The diagnosis of adrenocortical carcinoma (ACC) may be difficult with conventional light microscopy, especially when the tumor is nonfunctioning. Until now, no specific adrenocortical tumor marker was available. The current study was undertaken to investigate the interest of the D11 MoAb for the diagnosis and prognosis of ACC. METHODS: Eighteen adrenocortical carcinomas, 10 primary adrenomedullary tumors, 20 primary hepatocellular carcinomas, 50 primary renal cell carcinomas, 5 primary lung carcinomas, and 18 intraadrenal metastases were analyzed immunohistochemically with the D11 monoclonal antibody. ACC were also evaluated for the expression of other tumor markers, including neuron-specific enolase, chromogranin A, S-100, Leu-7, vimentin, KL1, AE1AE3, and epithelial membrane antigen. Relationships between clinical features and results of immunohistochemistry were also sought. RESULTS: Nuclear D11 staining appears to be highly specific for normal adrenocortical cells and related tumors. Nuclear D11 positivity was demonstrated in 44% of ACC and was restricted to well-differentiated tumors. No cytoplasmic or nuclear D11 staining was observed in adrenomedullary tumors. D11 reactivity confined to the cytoplasm was found in 5 of 18 adrenal metastases, in all 20 hepatocellular carcinomas tested, in 3 of 5 lung carcinomas, and in 1 of 50 primary renal cell carcinomas. Patients with nuclear D11 immunostaining were initially seen with metastases less often and survived longer than those with no nuclear D11 immunostaining (P < 0.05). CONCLUSIONS: Nuclear D11 immunoreactivity may help to differentiate ACC from intraadrenal metastases and adrenomedullary tumors. This also selects a group of ACC patients with a more favorable outcome.

Adolescent↗